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The online campaign comes at a time when President Afghan Ghani’s government is struggling to stop a Taliban onslaught. The #SanctionPakistan trend being promoted and amplified on Twitter by some Afghan users including politicians and journalists will further strain relations between neighbours and particularly affect Afghan refugees, analysts say. Pakistani authorities say the ‘Sanction Pakistan’ hashtag has been used for years by Indian accounts in the war of narratives that’s often played out on the internet. But the trend once again surfaced in recent weeks as Taliban insurgents took control of one Afghan city after another in a setback to Afghan President Ashraf Ghani’s government, which is losing control over the war-torn country. “There are certain people who blame Pakistan for everything because it’s very easy. I think the situation on the ground is much more complicated than that,” says Thomas Johnson, the author of Taliban Narratives: The uses and power of stories in the Afghanistan conflict. The lightning blitz with which ragtag Taliban fighters have pushed back Afghan forces has much to do with the failings of the Ghani government, he says. “You also have to look at the Kabul government’s corruption and it’s lack of legitimacy. You have a wide variety of reasons to assess (for what’s unfolding in Afghanistan).” Almost all of the $4.3 billion needed to pay salaries and other war-related expenses of Afghan government forces this year comes in foreign funding. If past experience is any guide then much of it will be siphoned off. The issue of ‘ghost soldiers’ who exist only on paper because the commanders have diverted salaries to their own accounts has long been a concern for American auditors in Afghanistan The Taliban have been successful in taking over chunks of Afghanistan because they were able to win over the local population in rural areas, says Johnson. The US-led forces drove the Taliban out after the 2001 invasion - many of the top commanders escaped to Pakistan where they regrouped. But when the insurgents re-emerged in 2004-05, they came up with a strategy. “Taliban recognised at the time that the center of gravity was the rural population. They used a wide variety of communication means to influence people - they used poetry, letters, and private radios,” says Johnson. “Kabul and the US never responded to that Taliban narrative. In the case of the US, they never really knew what the rural population wanted.” Some reports have tried creating an impression that #SanctionPakistan trend is something endorsed by most of the Afghans - even though only a miniscule percentage of the population has access to English-language social media. Pakistan’s National Security Advisor Moeed Yusuf has pointed fingers at Afghan and Indian twitter accounts for starting the ‘Sanction Pakistan’ to malign Islamabad. "It's not our fault. You must look at the Afghanistan map and see the territories captured by the Taliban. They are mostly areas which are far off from Pakistan," he said at a press conference on Wednesday. Despite the vitriolic online attacks against Islamabad and Pakistan’s armed forces, Afghan refugees - especially those in need of medical aid - continue to head towards the border of its eastern neighbour. “It’s very unfortunate what’s happening. Pakistan is always the convenient scapegoat for the Kabul administration and the US,” says Amina Khan, a director at Institute of Strategic Studies Islamabad. Khan cited the recent meeting of the United Nations Security Council (UNSC) on Afghanistan in which Pakistan wasn’t invited despite being the most important regional country that has a stake in Afghanistan’s stability. "I fear that those who will be worst affected by this propaganda are Afghan refugees. Pakistan is home to more than 3 million Afghans,” she says.

International Relations and Political Conflicts

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NEW DELHI: As U.S. troops marched into Kabul alongside the rag-tag militia of the Northern Alliance in 2001 and the Taliban melted away into the countryside, Afghan émigrés from across the world came flooding back into the city. Kabul Inter-Continental hotel was a hive of activity; the well-heeled, foreign-educated Afghan rubbing shoulders with powerful warlords and their side-kicks, all vying for public office after years of Taliban’s oppressive, misogynistic rule. One of the high-profile residents of the hotel on the hill to whom everyone gravitated towards in those heady days filled with hope of a better future was Zalmay Khalilzad. Well before his formal appointment as the U.S. ambassador to Afghanistan two years later, the Afghan-born, U.S. educated diplomat always had a great sense of his place in history. Nineteen years on, this February, everything that ‘Zal’ Khalilzad believed he had worked for—an Afghanistan ruled by moderate Afghans—seemed to have come to fruition. Or had it? For a giddy 24 hours last Saturday, it looked as if he had pulled off a deal to finally hold off the enemy that had preyed on NATO and ISAF-backed Afghan forces with impunity. But the Taliban’s new political chief Mullah Abdul Ghani Baradar didn’t even wait for the ink to dry on this ‘peace’ deal with the non-existent Islamic Emirate of Afghanistan—the name of the Taliban state when they held Kabul from 1996 to 2001. It was back to business as usual with Taliban forces on the rampage, first in Kunduz and then Helmand. It smacked of the first U.S. president, former President Barack Obama, openly declaring a troop withdrawal in December 2009, only to find they couldn’t. Is this where Trump is headed? Making an announcement that will win him plaudits at home but will be impossible to keep? With Khalilzad playing to the aspirations of only two of three stakeholders—the United States, whose president wants a quick exit of troops as a boost to his electoral campaign; the Taliban, who just want an emirate; the Afghan political leadership left rudderless—it’s a deal that is more optics than reality. Khalilzad and Donald Trump may want to avoid a repeat of the last time a superpower exited this ‘graveyard of empires’, as in 1988-1989, when the Soviets became sitting targets for the U.S.-armed mujahideen. U.S. troops cannot become a target of the Taliban and its affiliate the Haqqani network who have especially close ties with Pakistan’s Inter Services Intelligence. The relationship dates back to the time the Haqqanis evacuated hundreds of ISI operatives from Kunduz to safety, as the U.S. invaded in 2001. Today, they operate with impunity from sanctuaries inside Pakistan and Afghanistan. In a sign of their continuing influence, Sirajuddin Haqqani (son of the founder, Jalaluddin Haqqani, with the other son Anas, vocal and visible at the Doha talks) authored a piece in the New York Times last week, where he talked up the peace talks. Second in command in the Taliban today and a known ISI hand, he reportedly lives in Peshawar under the ISI’s protection. Was the aim of the op-ed to lull ordinary Americans into the false premise that the Talibs were sincere about wanting peace? How false that supposition is became evident when within 48 hours of the deal, the Taliban had unleashed its firepower on Afghan and U.S. army bases across the country. And the U.S. military hit back. The U.S. military, unlike the White House, is under no illusion over the Taliban’s intent. As Gen. Mark Milley, the chairman of the U.S. Joints Chief of Staff said on Monday: “I would caution everybody to think that there’s going to be an absolute cessation of violence in Afghanistan. That is probably not going to happen.” The Taliban’s time-worn strategy of keeping up the pressure on the battlefield to extract more concessions in the next round of negotiations has been all too clear. If U.S. and foreign forces do begin to exit over the next 14 months as laid down in the deal, reducing numbers from an already pared down 14,000 to 8,600 across five army bases, Afghan forces will be vulnerable, given that the last buffer between them and the Taliban will be gone. The bigger flaw is that the key third party, the incoming elected government of President Ashraf Ghani, already on the back foot over questions of its electoral legitimacy from main rival Abdullah Abdullah, is chafing at being pushed into doing business with an enemy no one fully trusts. The agreement directs the Ghani dispensation to empower a negotiating team to sit across the table with the Talibs in Oslo on March 10 in an intra-Afghan dialogue that aims to arrive at a permanent cease-fire and a power-sharing agreement between the rival Afghan groups. Ghani did sign a joint declaration with U.S. Defense Secretary Mark Esper and NATO Secretary General Jens Stoltenberg, which pins him down to holding negotiations with the Taliban and gives Afghanistan a security cover during the process. In rejecting the main point of the agreement, the handover of over 5,000 Taliban prisoners kept at Bagram air base in return for 1,000 men being held by the Taliban, Ghani could be flexing his muscles. A negotiating tactic, he may be making it difficult for the U.S to replace him with another Pashtun. With reports indicating that the paperwork to release the Taliban has already begun at Bagram, Ghani’s tenuous position is obvious. He needs the backing of the U.S. to stay on. At the same time, he cannot be seen as the foreign ‘stooge’ that the Taliban accuses him, and indeed, the entire political leadership, of being. Caught in the middle is the ordinary Afghan, paying the price for this ethnically driven fratricide, rooted in tribal rivalry that pits the majority Pashtun on the one side against the Tajik, Uzbek and the Hazara minorities. The buzz is that a Pashtun replacement for Ghani could be either former president Hamid Karzai, or Omar Zakhliwal, the current ambassador to Pakistan, who worked with the U.S. and Pakistan to bring about the release of Taliban leader Mullah Baradar, from a Pakistan jail so that he could front the talks with Khalilzad. Baradar, incidentally, was released from a Pakistan jail last year after being incarcerated for over eight years. But the manner of his sudden arrest in Karachi just as he had reached out to the Karzai government has always given rise to speculation that his descent into a drug-addled zombie while in jail, was to ensure that he would not go against Pakistan’s plans to scuttle Taliban-Afghan peace overtures. Baradar was one of the few in the top rungs of the Taliban who had repeatedly called for peace talks with the Hamid Karzai government. Said to be Mullah Omar’s brother-in-law, and whom he reportedly drove to safety as U.S. troops came in, he is also said to have saved Karzai when Jalaluddin Haqqani hunted down and killed the one-legged Commander Abdul Haq, with whom Karzai was putting together an anti-Talib force in 2001. In fact, Pakistan’s release of Baradar raises the big question on where Pakistan’s ISI which has long played puppeteer to the Taliban will stand post the inevitable return of hostilities on the ground. And where that will leave India, whose investments to the tune of $3 billion apart and the enormous goodwill it enjoys as a home to thousands of Afghan students, could all be in jeopardy. The leader of the India-friendly Northern Alliance, Abdullah Abdullah, a target of the Taliban has been a trenchant critic of Pakistan’s active backing of Taliban sanctuaries in North Waziristan that kept the Afghan government’s writ limited to Kabul and the north. There are conflicting reports on the Panjsheri leader being actively wooed by Islamabad, with other insiders saying his grand coalition that draws in Uzbek strongman Abdul Rashid Dostum, former Balkh governor Ata Mohammed Noor, Hazara chief Mohammed Mohaqiq and even Ismail Khan of Herat could see a possible vivisection of the country, that is already effective on the ground. Adding to the confusion is where that leaves the ambitious Amrullah Saleh, the former intelligence chief in the Karzai government, the chief point of contact between the U.S. and Kabul, for years, and opposed to any overtures to the Taliban that Khalilzad, during his tenure as three time ambassador, repeatedly attempted. The assassination of former President Burhanuddin Rabbani by the Haqqani network, which operates as an arm of Pakistan’s counter-intelligence unit, was only one of many outreaches that would go awry. Saleh, who contested on President Ashraf Ghani ticket as his vice president, wrote in a recent piece in the New York Times, hours before Khalilzad would close the deal with the Taliban in Doha, of how, despite he and his hapless family including his sister being a target, he was now willing to give the Taliban a chance. Saleh, was once a close aide to Northern Alliance chief Ahmed Shah Massoud, who was eliminated, only days before 9/11, by Osama bin Laden’s Al Qaida, which at the time had been given protection by the Taliban leader Mullah Omar, even after 9/11. For the Taliban—and their ISI mentors across the border—the deal is exactly what they had hoped for, bringing about a withdrawal of all foreign forces, opening the door to retaking of Kunduz, Kandahar and Kabul, when the time is right. The presence of the Pakistan foreign minister Shah Mahmood Qureshi at the Doha venue and his statement thereafter that talks between Pakistan and Afghanistan cannot be mandated by the peace deal is a tell, if needed, that Pakistan has the upper hand and will not be dictated to. Without Pakistani goodwill, the U.S. cannot execute a safe and secure troop withdrawal. That the Taliban have not signed off on to a promise not to provide safe havens to terrorists, denounce terrorism and sever links with Al Qaida and ISIS raises the question on who will police the deal. The Indian envoy from Qatar’s attendance at the Doha signing, preceded by the visit to Kabul by new foreign secretary Harsh Shringla, and the statements by the Minister of External Affairs S. Jaishankar on adopting a wait and see approach, raise eyebrows on what possible gains could come India’s way, if it means a return of the Taliban. Delhi’s much vaunted push for Afghan products to get market access to India through the Zaranj-Dalaram highway that it built, and to Central Asia through the Iranian port of Chabahar that it hopes to have access to, and through direct flights from Afghan airports, will require a friendly government in Kabul. Given the Taliban’s past propagation of conservative Islam, even India’s soft power through its freewheeling music and Bollywood movies will be severely constrained, in a Kabul where young people of all sexes have thronged its theatres, and profusion of eateries. Independent analysts like Sumeer Bhasin, says that its time India stops looking at Afghanistan through a Pakistan prism, pointing out that the Taliban have never expressed any interest in taking their subversive movement into Indian territory. Although, it must be said both the Mumbai attack and Kashmir terror infiltration have the imprimatur of the Lashkar-e-Toiba and its offshoots which were born, nurtured and trained in the crucial years when the Taliban allowed Al Qaida to flourish. Bhasin believes that there is a moderate element in the Taliban which wants India to grow into the role of a strategic influencer and counterbalance the hold of Pakistan over its rank and file. There is little proof of that. But with the world watching, Pakistan may no longer be able to provide safe sanctuaries to terror groups like the Haqqani network that are avowedly anti-Indian. As the U.S. wrestles with the fallout of its military’s domination of foreign policy and the counter-narrative provided by strategic thinkers like Khalilzad who seek to extricate it from Afghanistan, it must know a hasty and ill-considered exit will leave largely lawless Afghanistan open to a complete meltdown. Simply put, the Doha deal, must be revisited. (Neena Gopal is a journalist and author. Views expressed in this article are personal.)

International Relations and Political Conflicts

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Secretary of State Antony Blinken on Monday offered repeated assurances to lawmakers that Americans and allies in Afghanistan will be brought safely out of that country but gave few new specifics on how federal officials will do that in the absence of military forces there. In his first appearance before Congress since the end of the military’s evacuation mission in Afghanistan — and the first public oversight hearing on Capitol Hill since the full U.S. military withdrawal there — Blinken said that work still continues to get individuals trapped in the Taliban country to safety. “We are in constant contact with American citizens still in Afghanistan who have told us they wish to leave,” he told members of the House Foreign Affairs Committee. “We will continue to help Americans – and Afghans to whom we have a special commitment – depart Afghanistan if they choose. “There is no deadline to this mission.” But that pledge (repeated often by Blinken in the two weeks since the evacuation mission ended) was met with skepticism and disdain by Republicans on the panel, several of whom called for the Secretary of State to resign over the “bungled” withdrawal from Afghanistan. “In the weeks before the fall of Kabul, I was on the phone with very high ranking officials at the State Department and the White House trying to save lives,” said Rep. Michael McCaul, R-Texas and ranking member of the foreign affairs committee. “We had Americans that couldn’t get out. We had interpreters that couldn’t get through. They are left behind, and they will be executed (by the Taliban).” About 124,000 individuals were airlifted out of Afghanistan in the last 18 days of August, ahead of the end of the nearly 20-year American military presence there. About 100 Americans still in Afghanistan have asked for assistance in escaping the country. Advocates — including veterans groups still in contact with individuals on the ground — say thousands more Afghan allies were left behind and now face retaliation from the Taliban for aiding U.S. troops over the years. Republicans on the committee labeled that a failure by Blinken and President Joe Biden. McCaul said the incomplete evacuation effort means that “Our standing on the world stage has been greatly diminished, our enemies no longer fear us, and our allies no longer trust us.” Democrats on the panel criticized their GOP colleagues for grandstanding during the hearing and ignoring decisions by former President Donald Trump in the U.S. departure from Afghanistan. Blinken echoed that blame in his statements. “We inherited a deadline, we did not inherit a plan,” he said. “The deal that the previous administration struck involved committing to remove all U.S. forces from Afghanistan by May 1 of this year.” But along with the political support, Democratic lawmakers still questioned Blinken on what will happen to individuals trapped in Afghanistan now, both those trying to leave and minority groups that may be oppressed by the new Taliban government there. Blinken promised to use “every tool at our disposal — through our diplomacy, through our economic assistance, humanitarian assistance, programmatic assistance” to address the issue. That includes naming a new senior official at the State Department specific to protecting women and minority rights in Afghanistan. He also vowed to work with outside groups on the continuing evacuation efforts, saying he is in close contact with more than 75 veterans organizations working with individuals on the ground. In response to another point of GOP criticism, Blinken dismissed concerns about military equipment left behind in the withdrawal and shown under Taliban control in recent weeks. “Our folks worked very hard to disable or dismantle equipment that we still controlled before we left,” he said. “What we see now is much of the equipment that was left behind, including what was in the hands of the Afghan forces that then fell to the Taliban, much of it ... is inoperable or soon will become inoperable because it has to be maintained.” Bliken is expected to testify Tuesday on Afghanistan before the Senate Foreign Relations Committee. Gen. Austin Scott Miller, former commander of U.S. Forces-Afghanistan, will testify in a closed briefing before the Senate Armed Services Committee later in the day. Leo covers Congress, Veterans Affairs and the White House for Military Times. He has covered Washington, D.C. since 2004, focusing on military personnel and veterans policies. His work has earned numerous honors, including a 2009 Polk award, a 2010 National Headliner Award, the IAVA Leadership in Journalism award and the VFW News Media award.

International Relations and Political Conflicts

9

Turkish President Recep Tayyip Erdoğan’s assertive remarks about American Muslims at a conference organized by a Turkish government-financed association in New York on Sunday were censored by his office on the Turkish Presidency’s official website. A Nordic Monitor study has revealed that the English edition of the official site that translated Erdoğan’s speech from the Turkish edition did not include some statements that American officials might not like. Addressing only a few American guests and mainly party members who came from Turkey with his official delegation at an event organized by the Turkish American National Steering Committee (TASC) to promote a book he wrote, Erdoğan devoted much of his speech to prejudices against Muslims and claimed that the “virus of Islamophobia” is more destructive, more lethal and more insidious than COVID-19. As Nordic Monitor reported yesterday, Erdoğan spoke about a huge religious compound built by Turkey in Lanham, Maryland, in 2016 at a cost of $110 million. The center is run by Turkey’s Religious Affairs Directorate (Diyanet) and has hosted many US Muslim figures including members of the Muslim Brotherhood. “The Diyanet Center of America, which we launched in 2016, continues to host joint activities [with US Muslims]. We didn’t build it only for Turks, we did it for all Muslims,” Erdoğan said. However, these statements were not included in the English translation on the official site. In his speech on Sunday Erdoğan also mentioned the newly built 36-story Turkish House, located just opposite the United Nations building in New York. The opening of the high rise, which caused quite a stir in domestic politics, was even described by some party members as the most successful event in the 500-year history of Turkish foreign policy. Erdoğan announced that the building would not only serve Turkish citizens but all US Muslims. “God willing, we will open our Turkish House opposite the United Nations [headquarters]. This monument of glory will serve as a home not only for our citizens but also for the US Muslim community. Inshallah, your new and united address will be this building,” he said. As in the Diyanet complex, the opening of this new building was not included in the English translation. That Erdoğan attaches great importance to it and showed it off by hosting foreign guests there were not included in the English news story. Other untranslated remarks are those in which he quoted from the Qur’an that do not carry any political message, encouraging people by saying that the pandemic will eventually end. Reminding that Allah gives the good news in the Qur’an that “there is an absolute ease behind every difficulty,” Erdoğan said that” as people who believe that behind every night there is light and behind every evil there is goodness and that with the grace of Allah, this calamity will be overcome as well.” Those who read the English version of Erdoğan’s speech on the official site did not encounter these lines, either. During his visits to America in past years, Erdoğan attended events organized by American Muslims and gave enthusiastic speeches like a kind of caliph. This year’s trip to the States saw less religious emphasis. One of the reasons was, firstly, that the Muslim Brotherhood, which Erdoğan used to reach many American Muslims, was declared a terrorist organization in the US. Secondly, the behavior of a caliph was not appropriate at this point in time given the fact that Biden is in office. However, Erdoğan did not neglect to come together in a modest meeting with American Muslims, the majority of whom were Turks. Meanwhile, a noteworthy development took place before Erdoğan departed the US yesterday. The pro-Erdoğan TASC withdrew from a declaration it signed with a little-known Jewish organization two days earlier that was described as the Erdoğan government’s nod to Israel. According to the declaration, TASC and the Orthodox Jewish Chamber of Commerce (OJC) aimed to “cooperate for the common good of Turkish Americans and Jewish Americans and to support relations between our homeland the United States and our respective motherlands, Turkey and Israel” through initiatives such as the Abraham Accords, a series of US brokered agreements in 2020 aimed at normalizing relations between Israel some Arab states. Erdoğan had previously described this as a betrayal of the Palestinian cause. In a short message on Twitter, TASC announced that due to the lack of proper consensus, it was withdrawing from the Joint TASC-OJC Declaration.

International Relations and Political Conflicts

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Say goodbye to plants: Synbio player Antheia earns new backers in quest to redesign flora-derived medicine manufacturing The age of synthetic biology is officially upon us with super-unicorns like Ginkgo Bioworks changing the game in terms of how investors view those cell engineering platforms. Now, a California company looking to do away with fragile flora supply chains in drug development has earned a new round of investment to chase its goal. Synbio player Antheia raised a $73 million Series B round it will use to advance its pipeline of compounds derived from a plant-alternative manufacturing process using whole yeast cell engineering, the company said Wednesday. The round was led by Viking Global Investors and included participation from Sherpalo Ventures and Hillspire. Antheia will aim to engineer and advance its first pharmaceutical compound developed through its yeast cell fermentation process as well as a range of key starting materials (KSM) and API, it said. Many of those precursor compounds are derived from plants with a supply chain Antheia described as “fragile” given environmental threats, including natural disasters and geopolitical conflict. The company’s engineering platform would, in theory, replace the need for complex plant-derived compounds altogether, using engineered yeast cells acting like a “miniature factory” to churn out molecules at commercial scale. The company has some early data backing up its claims, with its first engineered KSM running at what the biotech calls “commercially relevant titers” at the pilot scale. Meanwhile, Antheia has achieved biosynthesis in four classes of plant-derived medicines, it said, including tropane alkaloids, the process of which was documented in a September article from CEO Christina Smolke in Nature. Those drugs, which are used to treat neuromuscular disorders such as Parkinson’s and muscle spasms, rely on the “intensive cultivation” of nightshades, Antheia said, due to the fact that there is no commercial-scale chemical synthesis process available. The supply chain for tropane alkaloids, including the antimuscarinic agent atropine used to reduce salivation before surgery and anti-nausea patches made with scopolamine, is particularly vulnerable to disruption, making it a ripe target for Antheia’s platform. To replicate the drugs, Antheia’s yeast platform had to express 26 genes derived from 10 organisms with eight gene deletions, underscoring the complexity of those drugs and Antheia’s engineering power. “Antheia’s synthetic biology platform can prevent drug shortages by enabling more resilient and agile production of essential medicines for the US and global markets, solving one of the most challenging problems in the industry and improving the overall healthcare system,” Smolke said in a statement. The three other plant-derived medicine classes where Antheia has achieved biosynthesis include antitussives, chemotherapeutics, and neurotransmitter inhibitors. Meanwhile, the company has eyes on “undruggable” classes of therapeutics given the potential to crack open areas of drug engineering where chemical synthesis isn’t possible. Synbio platforms have come a long way in recent years as companies that once couldn’t hold investors’ attention are now scoring massive public offerings and fundraising rounds. The largest, by far, is Ginkgo Bioworks, which went public in May as part of a reverse merger that valued the company pre-money at a whopping $15 billion. Ginkgo scrapped for years to earn that valuation, working on areas as diverse as perfume and synthetic meat before their commercial-scale drug manufacturing process went viral. Meanwhile, companies like Zymergen, using cell fermentation to produce industrial materials, are also seeing a wave of new interest. The biotech closed a $500 million IPO in April with the ambitious goal of using its platform to disrupt a potential $3 billion industrial materials market.

Biomedical Research and Healthcare

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The ID resolver uses the files in the specified directory to create a large map. The key for the map is the unique identifier (the MOD ID, for example the MGI:, RGD, FBgn, ZFIN: identifiers). The values in the map are all the symbols, old identifiers, dbxrefs (e.g. Ensembl). |unique gene identifier||symbol, name, ensembl ID …| |MGI:97490||pax6, paired box gene 6 …| The ID resolver then uses this map to replace old or non-unique identifiers with the unique identifier. This allows genes to be merged correctly into the database, and lets each mine be interoperable with other friendly mines. The ID resolver is used in several data sources, Homologene for example. If you look at the Homologene data, you'll see they don't use the MGI identifier. See: When parsing the Homologene data file, the ID resolver replaces the symbol "Pax6" with the MGI identifier. The parser sets MGI:97490 to be the primary identifier then stores the gene to the database. Similarly, it replaces Pax6 with "RGD:3258" for the rat gene. And so on. |EntrezGeneIdResolverFactory||NCBI gene info for a collection of organisms||ftp://ftp.ncbi.nih.gov/gene/DATA/gene_info.gz| |FlyBaseIdResolverFactory||flybase chado db, for ‘’D.melanogaster’’ only||ftp://ftp.flybase.net/releases/current/psql flybase chado| |WormBaseChadoIdResolverFactory||wormbase chado db, for ‘’C.elegans’’ only||modENCODE specific| |HgncIdResolverFactory||HGNC human gene ids||Uses the biomart service at http://www.genenames.org| Many data converters use the Entrez (NCBI) Gene ID resolver: Download the identifier file - Unzip the file to Create a sub directory /DATA_DIR/idresolver/as file root path and a symbolic link entrezto the file$ cd /DATA_DIR/idresolver/$ ln -s /DATA_DIR/ncbi/gene_info entrez Add the root path to the file in Id resolvers and corresponding symbolic to data file: In the data converter, the ID resolver is given an identifier. The resolver then looks in the map for the identifier. |number of matches||returns| A factory will find data root path from ~/.intermine/MINE_NAME.properties, path needs to be absolute. the key and the symbolic link of the data file need to be hard-coded in factory class, e.g. in As for database case, e.g. flybase chado the key also needs to be hard-coded in factory class, e.g. in FlyBaseIdResolverFactory The Entrez gene identifier source has a configuration file, entrezIdResolver_config.properties. You shouldn't have to edit this file. This config will parse fruit fly identifiers, e.g. FLYBASE:FBgn0088803 If you don't want to strip the prefix from the identifier, use this config: Warning The EBI changed how they format their data. If you have a recent data file, you do NOT want the above configuration for MGI. To replace a taxonomy identifier with a strain, use the following: To ignore certain organisms, do this: IdResolverService is a java class providing static methods to get id resolver directly. It's also the most straight forward way to create an id resolver. For example, to create a fish id resolver by taxon id in a converter: You can use the IdResolverService to create resolver by taxon id, a list of taxon ids, or by organism, e.g. As the resolver maintains java maps of one or more organisms' identifiers, you must explicitly tell it which organism you want it to resolve for, e.g. It is also possible there are two or more matching primary identifiers for a particular identifier, in this case, discard this identifier, e.g. An IdResolver factory will create an IdResolver which will read and parse data from a file or database containing identifier information, to save them to a Java map which will be written to a cached file. The new factory class needs to inherit super class IdResolverFactory: Multiple taxon ids: Multiple files or mixture of file and db: Add resolver factory to IdResolverService: - generalized resolver factory which will read a configuration file to be aware of identifier information by column. e.g. type=tab, column.0=mainId, etc.

Biomedical Research and Healthcare

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When viruses invade microbes, many of the microbes die, but those that survive will grab some of the virus’s DNA and insert it into a CRISPR spacer. The microbe can then use this viral DNA to identify future viral invaders and target them for destruction. Cas enzymes are guided to viral DNA and then chop it up, so that the virus cannot replicate. Scientists discovered that they could use this CRISPR-Cas system to enter a cell, snip out any segment of DNA that they targeted, and then have the cell stitch a new gene into the open space. Moreover, they could do this not only for somatic cells, but also for germ cells (eggs and sperm). Doing it for germ cells would mean that the genetic changes would be passed down by the biological inheritance of offspring. Recent research has shown that this can be done with human embryos. This suggests the possibility that parents could use this technique to genetically enhance their children with genetic propensities for better bodies and better minds, and that this redesign of the human genome could be passed down by inheritance to the next generation. Properly understood, this should teach us at least three lessons about human evolution—lessons about the Lamarckian character of biological evolution, about the natural sources of technological evolution, and about how evolved human nature limits the power of genetic technology. First, notice that CRISPR is an adaptive immune system that learns from its experience with the viral enemies of microbes and passes on what it has learned to the descendants of the microbes. It has been generally assumed that Jean-Baptiste Lamarck’s theory of the evolutionary inheritance of acquired traits has been refuted by Darwinian biology. Actually, Charles Darwin himself accepted Lamarckian evolution as one of the mechanisms of evolutionary change. And CRISPR shows that Lamarckian inheritance really does occur in nature. Using CRISPR for the genetic engineering of children could become a form of intentional evolution in which parents use scientific knowledge and technology to direct the evolutionary inheritance of acquired traits for the improvement of human life. The second lesson here is about the natural sources of the technological evolution of genetic engineering. We might see genetic engineering as manifesting the modern scientific project, first proposed by Francis Bacon in the seventeenth century, for the human mastery of nature for the relief of the human estate. We might think that such a conquest of nature requires the human invention of artificial tools. But notice that CRISPR is not a human invention but something that scientists discovered in nature. Microbes have been using CRISPR to edit their DNA for millions of years. Once we understand how this works in nature, we can then use it for genetic engineering. This confirms Bacon’s observation that “nature to be commanded must be obeyed,” because “all that man can do is to put together or put asunder natural bodies,” and then “the rest is done by nature working within.” And thus we should see how the power of biotechnology is limited by the potentialities inherent in nature. That leads us to the third lesson—how evolved human nature limits the power of genetic technology. A realistic assessment of genetic engineering avoids both the exaggerated hopes of the optimists and the exaggerated fears of the pessimists, because we should see that genetic engineering will always be limited in its technical means and its moral ends. It will be limited in its technical means, because an individual's traits of personality and intelligence arise in unpredictable ways from a complex interaction of genes, brains, life history, and social environment that is not determined by one or a few genes. Genetic engineering can possibly eliminate some genetic disorders that are strongly influenced by a few genes. But the complex traits of the human mind are not genetically determined in any simple way. example, proponents of human genetic engineering often say that it will allow parents to increase the innate intelligence of their children by selecting those genes that enhance intelligence. But while there surely is some genetic contribution to human intelligence, research in behavioral genetics suggests that intelligence arises as much from environmental factors as from genetic propensities. Moreover, the genetic basis of intelligence depends on so many genes interacting in such complex ways that it will be impossible to control this through changes in one or a few genes. Even if we could explain exactly the multiple genetic causes of intelligence, we would still have to explain how these genes influence neural activity and how genetic propensities and neural activity interact with environmental contingencies in the unique life histories of particular human beings. And all of this would presuppose that we could agree on how to define and measure “intelligence,” even though both scientific research and common-sense experience suggest that there are different kinds of intelligence—for example, analytic intelligence, verbal intelligence, practical intelligence, musical intelligence, and kinesthetic intelligence. For all of these reasons, we are unlikely to ever succeed in the genetic engineering of intelligence. Genetic engineering will also be limited in its moral ends, because parents will want to use this technology to improve the chances that their children will be healthy and happy, and thus the parents will be guided by the same natural desires of our evolved human nature that have always motivated parents in the care of their children. For these reasons, we should welcome genetic engineering as helping us to treat some genetic disorders, but we should not expect that it will ever fundamentally transform human nature. We should give up both the utopian hopes of the transhumanists and the apocalyptic fears of the bioconservatives. Some of my previous posts criticizing genetic determinism can be found here

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A system that allows researchers to control a tiny cellular transport network has been developed by researchers at the Universities of Oxford and Warwick. In the system DNA acts like a foreman on the nanoscale construction site, assembling and directing the operation of shuttles that transport molecular cargo along cellular components called microtubules. 'DNA is an excellent building block for constructing synthetic molecular systems, as we can program it to do whatever we need,' said Adam Wollman, who conducted the research at the University of Oxford's Department This set-up served as the inspiration for the system. 'One of the more sci-fi visions of nanotechnology is the creation of moving "nanobots", but it turns out that nature got there first', said Wollman, speaking to the online magazine Motherboard. The Oxford team fused the kinesin with a short, synthetic DNA strand loaded with information for either assembly of the network or transportation. 'Assembler' nanobots were made with two kinesin proteins, allowing them to move tracks around to assemble the network, whereas the 'shuttles' only need one kinesin protein to travel along The group used fluorescent green dyes as cargo to demonstrate the system, a method inspired by melanophore, a pigment used by fish cells to control their colour. 'We first use assemblers to arrange the track into spokes, triggered by the introduction of ATP (adenosine triphosphate), then send in shuttles with fluorescent green cargo which spread out across the track', explains Wollman. 'When we add more ATP, the shuttles all cluster in the centre of the track where the spokes meet'. The system also allows the researchers to reverse the process, or 'demolish' the site, by programming the shuttles to signal the cargo-carrying shuttles to release the fluorescent cargo into the environment and dismantle the tracks. The developers of the self-construction system say it has the potential to speed up chemical reactions used in biotechnology by bringing the necessary compounds together into a central hub.

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Dr Goldberg explores the impact of the psycho-spiritual on both the development and treatment of cancer. It is possible to manage cancer in an integrated way by removing all external and internal environmental agencies that promote cancer growth, creating a positive lifestyle that supports healthy protective systems and providing medicinal substances and therapies that contain cell proliferation and strengthen the immune system. As an extension of this integral approach to cancer treatment, we focus here on the inner psycho-social factors which work as chronic irritants to either activate cell proliferation or weaken cell containment. Central to all these interventions is the patient himself or herself for whom the integrated programme is designed. For the way in which the individual will work with therapy is crucial: the patient, if willing, has the potential to develop mental skills to aid in the removal of these psycho-social irritants. THE DEVELOPMENT OF CANCER Cancer develops, when cells of the body begin to grow abnormally and are no longer controlled by the normal surveillance and regulative forces of the body. These are highly complex immune, bio-chemical, genetic and psycho-spiritual functions, the understanding of which are driving modern cancer research today. The goal in treating cancer effectively must be to destroy the unbridled cancer cells directly, or to strengthen those innate containing activities that destroy cancer, without harming the healthy cells of the body. THE ROLE OF THE PSYCHO-SPIRITUAL IN DISEASE - Do the mind and the emotions influence the development of cancer? - Can the mind be harnessed to help fight cancer? These two questions have intrigued me ever since I began to treat cancer in an integrative way over 40 years ago. During this time I have sought ways to understand these connections and to incorporate this self-healing potential into an integrative cancer treatment programme. There is growing scientific evidence to show that the outcome of an illness is influenced by active participation in the treatment process. The work of Jon Kabbat Zinn and other researchers using mindfulness-based approaches show the improvement in illnesses when the patient is involved in his treatment programme.¹ In my practice I have found this most certainly to be the case. Cancer patients who have a positive mindset do significantly better than those with a negative attitude to their illness and their long term survival. It is also well established that emotions such as anxiety, depression, bitterness, guilt, and suppressed feelings affect brain, endocrine and immune functions negatively, whereas joy, laughter, relaxation and creative activities do the opposite. One such article in the European Journal of Cancer linked emotional stress with weakening of the immune system. This paper concluded that ‘psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways.’² The well-accepted science of psycho-neuro immunology has documented hundreds of studies showing the links between the psyche, the brain and the immune system. Multiple studies show that stress especially contributes to increased mortality from already established cancers.3-5 THE RESPONSIBILITY OF THE PATIENT Self-reflection and self-awareness can guide the patient towards taking responsibility for the deep-seated emotions that can play a role in developing and keeping cancer. The subconscious soul life harbours a host of different personality sub types. We are constantly moving from one sub type to another depending on our changing circumstances and inner responses. When we need approval, we will want to please, when we feel threatened, we may become angry. In one day, a person can express assertiveness or submissiveness, confidence or doubt, fear or courage, gentleness or harshness depending on our internal responses and our interaction with a constantly changing environment. When we turn our attention to these personality sub-types, we identify them and determine whether they are helpful or harmful to our well-being. We discover that we are able to influence their habitual nature by calling up other parts of our personality that can change the behaviour pattern. NEGATIVE PERSONALITY SUB-TYPE Early on in life Ms AB learned to suppress feelings because her parental environment did not permit the expression of feelings of vulnerability. This sadly became a habitual pattern in all her relationships. At the same time she learnt to become an achiever because this was encouraged at home and at school. Her ambition drove her to become a top executive, and she chose to put her energies into her work while avoiding committed relationships. A year after her mother died of breast cancer, she herself was diagnosed with the same illness. Ms AB wanted to do everything in her power to overcome her illness. She was well aware that a mastectomy followed by chemo and radiotherapy was no guarantee that her cancer would not relapse. She realised she had a psycho-social disposition for this illness, that years of suppressed feelings had disturbed her neuro-endocrine and immune functions. The final stress of her mother’s death, where she was unable to grieve or show her emotions, was, in my opinion, the trigger that led to the cancer growth. If cancer patients are to bring themselves to the core of their integrated healing process and feel in control and empowered, they need to clear their healing path from psycho-spiritual obstacles which in the course of their lives have compromised their wholeness, dignity and strength. Participatory Counselling, based on Psycho-phonetic Counselling developed by Yehuda Tagar, is a methodology for accessing and exploring such deep-seated psycho-social patterns. Psychophonetics regards the human being as a living body, soul and individual spirit with a potential connection to vast resources of vitality, creativity, intelligence, compassion, intimacy, expanded awareness and spirituality. Ms AB committed herself to doing several counselling sessions. She had to find the real living partner in herself who ‘wanted to do everything in her power to overcome her illness.’ She had to learn to play this role authentically. This was the role player who undertook to direct her integrative treatment programme and to sort out her internal blocks. She had to find the courage to meet that part of her personality that was terrified to express her feelings. She had to discover another part that was willing to show her feelings. She began to engage and participate actively in the different personae of her own psycho drama and started the transformative work of applying this to her social life, and changing her old habits. She discovered a growing sense of liberation from her own incarcerated emotional life and had the real sense of a healing taking place in her body and mind. Above all she felt that she was in control of her own healing. It was as if she had found her internal physician. Self-healing in a nutshell - Be willing to participate in your therapy - Become aware of the state of your soul life - Access your deep-seated emotions and explore them with courage - Show your feelings - Walk the talk: apply your new positivity to everyday living - Enjoy your liberation from mental and physical ill health When cancer patients learn to take full responsibility for their own healing and to participate in their healing transformation, the outcome of their illness can be shifted significantly. This participatory approach to medicine opens up a new way of diagnosing and treating illness, one in which both patient and healing practitioner participate actively in the healing process. Participatory Counselling / Psychophonetics has become an active and essential part of my practice: please feel free to contact me should you be in need of help. - Kabbat Zinn J. Participatory Medicine. JEADV. 2000; (14): 239 – 40. - Kiecolt-Glaser J.K, Glaser R. Eur J Cancer. 1999 Oct; 35(11):1603-7. - Herbert, T.B. et al. (1993) Stress and immunity in humans: a meta-analytic review, Psychosomatic Medicine. 1993. (55):364–79. - Irwin, M. et al. Human Psychoneuroimmunology. Oxford University Press. 2005. - Pert, C.B. Molecules of Emotions. Pocket Books. 1997.

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The cytoskeleton – a collection of polymeric filaments, molecular motors, and crosslinkers – is a foundational example of active matter, and in the cell assembles into organelles that guide basic biological functions. Simulation of cytoskeletal assemblies is an important tool for modeling cellular processes and understanding their surprising material properties. Here, we present aLENS (a Living Ensemble Simulator), a novel computational framework designed to surmount the limits of conventional simulation methods. We model molecular motors with crosslinking kinetics that adhere to a thermodynamic energy landscape, and integrate the system dynamics while efficiently and stably enforcing hard-body repulsion between filaments. Molecular potentials are entirely avoided in imposing steric constraints. Utilizing parallel computing, we simulate tens to hundreds of thousands of cytoskeletal filaments and crosslinking motors, recapitulating emergent phenomena such as bundle formation and buckling. This simulation framework can help elucidate how motor type, thermal fluctuations, internal stresses, and confinement determine the evolution of cytoskeletal active matter. ASJC Scopus subject areas - Biochemistry, Genetics and Molecular Biology(all) - Immunology and Microbiology(all)

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Remember when you couldn’t go on the Internet without seeing a friend or celebrity getting doused with a bucket of cold water? That was actually five years ago … when the ALS Association’s wildly successful “Ice Bucket Challenge” went viral and brought in a sudden $115 million to the fight against amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease. In a recent story for The Chronical of Philanthropy, writer Emily Haynes outlines how the ALS Association is using the fifth anniversary of that success to report back on what it has accomplished with the Ice Bucket money. Her story, “Cold Cash: What to Do When Unexpected Money Pours In,” is a case study on how to convey the impact of giving dollars. The ALS Association is marking the anniversary with a new fundraising campaign and a commitment to tell the story about how the money was used. And the organization has a good story, Haynes writes. “It has spent $80 million to fund research breakthroughs that are likely to prolong lives of those afflicted with the ailment, and it has improved treatment for many patients.” But can the organization sustain that research spending? That question is less clear given that less than 1 percent of first-time givers during the challenge has donated again. While the ALS Association “has not done well with repeat donors” in the five years since the challenge, it has tried hard to understand what supporters want. The organization recently surveyed its current and lapsed donors about their giving motivations, asking how they’d like the association to use their donations as well as how they’d like it to communicate with them. “What they wanted,” says Tina Zeff, the association’s executive vice president for development, “was to understand and achieve the greatest impact: treatments and a cure.” The ALS Association does not expect to repeat the magic of the Ice Bucket Challenge. “To plan on that is not, in my estimation, what our community deserves,” Zeff says in the story. “They deserve for us to be around serving our mission for years to come, until we work ourselves out of a job, and treatments and cures are found.”

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EFFECTIVENESS OF THERAPEUTIC COMMUNICATION TO THE ANXIETY OF PATIENT WITH CHEMOTERAPHY OF NASOPHARING CANCER IN CHEMOTERAPHY OF NASOPHARING CANCER IN CHEMOTHERAPY ROOM OF RSUD Dr. PIRNGADI MEDAN OF 2016 Silalahi, Elny Lorensi Sidabutar, Asmi Naomi MetadataShow full item record AbstractAnxiety occurred when patient dealing directly to the threat of health and prosperity. Chemotherapy is classification of medical therapy that cause anxiety because there is threat on the physics and spiritual integrity of anyone. The anxiety is caused by fear, frustration, conflict or general respond to the pressure and unfamiliarity (the lack of information/communication from the nurse). The formulation of problem : is there effectiveness of therapeutic communication to the anxiety level of patient in take of NPC chemotherapy in chemotherapy room of RSUD Dr. Pirngadi Medan of 2016. The objective of this research is to study effectiveness of therapeutic communication to the anxiety level to the patient with NPC chemotherapy at RSUD Dr. Pirngadi Medan in 2016. This research is Quasy Experimental with one group Pretest-Posttest design in which on this design there is pretest, before comunication and posttest after communication and observed by questionnaire. The sample procedure in this research is accidental sampling. Based on result of research it indicates that majority after the therapeutic communication, the data without anxiety is 6 persons (60%) and the mild anxiety for 3 persons (30%) and medium anxiety for 1 person (10%). - PANNMED

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The following is a guest post from Elite HRV, a top-rated HRV mobile app that was created by a small group of Paleo-enthusiasts that decided to leave their day-jobs and come together to make a difference. They are passionate about helping people reach their health and performance goals and believe that heart rate variability is one of the most powerful tools available to achieve this. It is becoming increasingly obvious that food intolerances vary enormously between individuals. This isn’t surprising: we all have different genetics, microbiomes, environments, and even maternal gestation lifestyles! One size does not fit all. As a result, more and more health-seekers are starting with a Paleo Diet, and then using heart rate variability (HRV) to identify and address specific food intolerances. Many end up adding certain foods back into their diets after careful testing. Why is HRV a practical tool? In this post, Paleo Leap explored how to measure stress levels and inflammation, and found heart rate variability to be a useful tool. HRV is useful for finding dietary offenders because it is: Systemic: HRV looks deep into the nervous system, which can give insight into the physiological impact of exercise, diet, sleep, and social stress. This means it can help narrow down diet as a source of inflammation. Easy: It can be tracked non-invasively in a few minutes per day. No need for 24/7 wearables, needles, blood or saliva samples. This allows you to track more regularly to isolate specific source of inflammation, such as specific foods. Responsive: The impact of various stresses show up in HRV instantaneously and can give daily insight into progress. No waiting around for weeks or months. Unlike most measurements, you can also repeat tests easily over time to gain more confidence that what you are testing is really the source of a change in your body. Individualized: HRV apps have become more advanced over time and some can now automatically identify personalized patterns in your stress, inflammation, and recovery. This goes beyond just comparing your data against reference ranges or estimates from a general population. 1. Download an HRV monitoring app that allows for open (i.e. unlimited time) readings specifically useful for these kinds of tests. We designed Elite HRV to accommodate this type of testing, and it is one free option. 2. Wear a heart rate monitor and connect with your app. Accuracy is very important for HRV hardware, and choices depend on which heart rate devices are compatible with your HRV app of choice. Some apps have proprietary hardware, but many apps can utilize a chest strap for accurate readings. In response to feedback on uncomfortable and inconvenient chest straps, patches and expensive wearables, we designed and are launching a finger-sensor option specifically for HRV that is open to use with almost any HRV app. 3. Start measuring HRV and relax for a few minutes before eating. If possible, avoid too much movement (like walking) and mentally stressful activities. 5. After eating, wait for an additional 10-15 minutes to see what kind of impact on HRV the digestive process is having. Try not to introduce major changes in activity (like getting up and walking around) or mental stress. Typically HRV may increase slightly with digestion, as the parasympathetic nervous system (the “rest and digest” arm of the autonomic nervous system) kicks in. However, if HRV decreases instead, it is a sign of activity in the sympathetic nervous system (“fight or flight”), typically a sign of inflammatory stress. In those cases, something in the food is likely the culprit! It’s important to note that in addition to an offending food, it may also be the total quantity of food, quantity of a specific food, or combination of certain foods that could be a trigger. For a “smoking gun”, eliminate the food(s) for 30 days, then test immediately after re-introduction. *Credit to experts such as Alessandro Ferretti in designing and testing this process. Alessandro Ferretti has published more details information on his website. Test, Improve, Re-Test Over time, many HRV users (including the entire Elite HRV team) have used this process to eliminate surprising inflammatory foods from their diet (eggs! tomatoes!), while introducing new foods as well (fermented dairy!) The road to better health starts with a great template – a Paleo Diet – and then continues with some tinkering and personalization. Don’t forget to enjoy the food along the way! Interested in HRV, but not the wearables? You’re not alone! Chest straps and other devices get in the way and aren’t practical. As we mentioned above, Elite HRV is the largest and top-rated HRV mobile app, with nearly 150,000 users. We also have a team dashboard to help coaches, teams, and clinics track the progress of their clients. Our main complaint was that wearables (i.e. chest straps) were the biggest frustration of tracking HRV. We delved into solutions and created CorSense. CorSense is a finger sensor that reads your heart rate variability in as little as 2 minutes a day. If you’re interested in learning more check out our KickStarter campaign that launched this September below. Note: Paleo Leap earns a commission on Kickstarter sales of the Elite HRV monitor (the CorSense).

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Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment The Human Genome Project, which set the goal of determining the complete nucleotide sequence of the human genome, was among the most important biologic research projects of all time. To capitalize on the enormous potential of having access to genome-wide sequence information, scientists, clinicians, engineers, and information scientists combined forces to develop a battery of new molecular and bioinformatic tools that now make it possible to obtain and analyze biologic datasets of unprecedented magnitude and detail. Generally referred to as genomic technologies, these approaches permit sequence analysis—as well as gene transcript, protein, and metabolite profiling—on a genome-wide scale. As a result, the Human Genome Project and the technologic innovations and computational tools that it spawned are having profound effects on biologic research and understanding. The application of these technologies to toxicology has ushered in an era when genotypes and toxicant-induced genome expression, protein, and metabolite patterns can be used to screen compounds for hazard identification, to monitor individuals’ exposure to toxicants, to track cellular responses to different doses, to assess mechanisms of action, and to predict individual variability in sensitivity to toxicants. Given the inherent complexity in generating, analyzing, and interpreting toxicogenomic data and the fact that toxicogenomics cannot address all aspects of toxicology testing, interested parties need to prepare in advance. This preparation will help them understand how best to use these new types of information for risk assessment and for implementing commensurate changes in regulations and public health, while preparing for the potential economic, ethical, legal, and social consequences.

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Objective: To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks' gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo). Study design: We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK. Results: All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of 'step-down' units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified. Conclusions: Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

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From where I sit, it seems to me that the entire landscape of Alzheimer’s disease (AD) has changed, and changed quite significantly. The litany of announcements from pharmaceutical companies big and small revealing the unfortunate news that yet another promising agent for the treatment of AD has failed to meet its objectives in a clinical trial and is being withdrawn from the “race” to approval, is familiar and increasingly depressing. The most recent and perhaps most disappointing of these were the failures of two BACE-1 inhibitors, one in a Phase III trial, the other in a Phase IIb/III trial. I have discussed those two drugs, and, especially, their highly promising mode of action, in a previous encyclical, and there will be more to say later on in this one. These failures, along with the many, many other failures to launch an effective drug for the treatment of AD, have had a dampening effect on AD research. For example, AD deaths have increased by 145% in the years from 2000 to 2017. Meantime, cancer deaths were declining; age-adjusted cancer mortality in the US declined by 26% from 1991 to 2015. But venture-capital funding for cancer during those overlapping years was much higher than for AD – $16.5 billion for cancer in the past 10 years versus $1.0 billion for AD. You can’t exactly blame the moneybags guys for their reluctance to bet on a proposition where the odds are at least 20 to 1 against scoring a hit. Those odds are calculated based on the fact that only four (five if you count a combo) drugs are FDA approved for AD, versus the hundred-plus flops. And the odds are probably even worse, considering that none of the approved drugs do more than slightly delay the progression of dementia, and a couple were already approved for Parkinson’s disease. So, if financial gain is the supposed motivation for investing in AD research, you can see why research into new drug development is slowing down. However, AD continues to receive considerable support from the Federal government. An additional $350 million were just added to the NIH budget specifically for AD research, bringing the total AD funding for the year 2020 to $2.8 billion. Overall, despite opposition From Above, Congress increased NIH funding for 2020 by about $3 billion, bringing the total funding to $42.1 billion. Much of that funding supports scientific research into Alzheimer’s rather than specific drug development. And there’s a great deal of that going on. According to PubMed, there are more than 149,000 papers on AD, and according to the Clinical Trials registry, more than 2,000 clinical trials in various phases. What we’re not seeing are clinical trials of drugs in later phases with the objective of treating dementia in persons with established Alzheimer’s disease. Before we get into the details, here’s an overview of the impact of AD in the US and the world. - 5.7 million persons in the US are currently diagnosed with AD. That’s diagnosed with AD; an equal number are thought to have undiagnosed AD, perhaps in the early stages. - This includes 200,000 persons under 65 years of age. - One in ten people 65 years old or older has Alzheimer’s dementia. That percentage increases with age; 32% of people 85 years old or older have AD. - Almost two-thirds of Americans with AD – 3.4 million – are women. The chief reason for this large imbalance is that women’s life expectancy is about 5 years greater than men’s life expectancy, and it’s in those 5 years that the incidence of AD increases steeply. - AD prevalence is expected to increase as our population ages. By 2025, 7.1 million Americans are predicted to have AD, and by 2050, the number is predicted to be 13.8 million. - The prevalence of AD and other dementias is about twice as high in African Americans and about one-and-one half times as high in Hispanic Americans as it is in non-Hispanic whites. The reasons for this are not entirely clear. The disparity is not thought to be due to genetic differences, rather to higher prevalence of conditions and circumstances which contribute to AD and dementia. We’ll go into some of those later in this post. - According to the Alzheimer’s Association, the 2019 costs to the nation associated with AD will be about $277 billion. About half of this cost will be paid by Medicare, and another significant chunk by Medicaid. Unless there is a treatment breakthrough, total costs may reach $1.1 trillion by 2050. - Annual Medicare costs per patient with AD are estimated to be about $24,000. For patients without AD the cost estimate is about $7,500. - These costs don’t figure in the huge economic impact of AD on caregivers, often the immediate family members of the person with AD. - AD is the 6th leading cause of death in the US. - The death rate in the 5 other leading causes of death in the US – breast cancer, prostate cancer, heart disease, stroke, and HIV – have all declined between the years 2000 and 2015, while the death rate from AD has increased by 122%. At present, there is no cure, and the most effective treatments do nothing to stop the progress of the disease. At best, they slow it. This, may I note, is not unlike some cancer treatments that have been deemed moderately successful. So, considering that Alzheimer’s disease is perhaps the most severe health threat to Americans and that drug development to manage this threat to our health, and indeed to our lives, has just about totally stalled, why is there not a vigorous public outcry to do something about it? It’s almost old stuff when presidents of the US proclaim vows to defeat cancer, but when it comes to AD, mum’s the word. Perhaps it’s because Alzheimer’s mostly affects older folks. It’s intuitively okay to accept AD as a natural consequence of aging, whether or not it’s an accurate assessment. And it also seems to be ethically much more justified to spend dollars on medical treatment of diseases that mostly affect children than on diseases of the elderly. Money spent on preserving the life of an 8-year-old child buys more life-years than an equivalent sum spent on extending the life on an 80-year-old geezer. As I see it, the prevailing view of AD separates the symptoms, primarily dementia, from the underlying causes, whether those might be the notorious amyloid beta (Aβ) or tau protein tangles, also called neurofibrillary tangles, or something entirely different. Essentially, the people working on Alzheimer’s have come to realize that those underlying causes can appear many years before any symptoms of dementia manifest themselves. Another complication emerges, notably that many elderly people (and many not so elderly!) exhibit traits of forgetfulness entirely unrelated to AD. The result is that by the time a diagnosis of AD based on symptoms is firmly established and other forms of dementia are ruled out, it appears that Alzheimer’s dementia may be irreversible. The brain is already severely clogged with amyloid beta or tau protein tangles, or possibly both, and there are no handy brain-clearing instruments or substances. The situation is further complicated by the reluctance of people to undergo procedures that might lead to a diagnosis of Alzheimer’s, whatever these procedures might be. Indeed, if a diagnosis of AD does not lead to a course of treatment that significantly improves the symptoms, why would anyone be willing to be subjected to diagnosis? The outcome of the diagnostic procedure is certain to be bad news. In the case of a positive diagnosis, it’s “Yes, you have Alzheimer’s disease, but we can’t do anything to stop it.” And if the diagnosis is negative, it’s “No, you don’t have Alzheimer’s disease. You’re just an old-timer who is losing his marbles.” A lousy verdict either way. In contrast, diagnostic procedures to detect many of the most common deadly diseases or conditions are downright attractive. Women don’t regard mammograms as pleasant experiences, but since mammograms have become widely accepted procedures (at least in most of the developed world) breast cancer mortality has plummeted. The same relationship holds true for many diseases. Most people accept these diagnostic procedures with a relatively optimistic frame of mind: if the outcome is positive – for example, the patient really does have breast cancer – effective treatment is available. And if the outcome is negative – no sign of breast cancer – it is received as good news. That is not the case with attempts to diagnose Alzheimer’s disease once it has taken hold. But a means of predicting AD in persons in whom the disease has not yet become established might be more attractive, especially if there are ways to stave it off. The basic premise of much current research is that once the brain has been invaded by those substances that gunk up the works, whether those are Aβ or tau tangles or something else, nothing seems to works to clear out the gunk. However, it might be possible to take steps to protect the brain from the gunk and keep it functioning as well and as long as possible. Thus, the focus of the scientific/medical/ pharmaceutical complex, with few exceptions, appears to be on finding means of detecting AD sooner or identifying the individuals most at risk for developing AD. Predicting Alzheimer’s Disease The simplest avenue to predicting AD would be a biomarker – some kind of tell-tale substance whose presence, whether in the blood or another bodily fluid, would suggest that the individual was on a path that would lead to Alzheimer’s. A test to detect such a biomarker could then be routinely included in a blood test, for example, and could then be an accepted part of a general physical examination. When a person has a physical exam, he/she is not being specifically evaluated for the risks of developing any particular disease, but the blood test will provide information to predict whether the individual being tested is at risk for a number of diseases/conditions. What that means is that a person doesn’t have to wait until he/she gets lost on the way to the grocery store to be evaluated for AD. The results of the simple blood test would constitute a simple warning sign: “AD may be on the way for you, and you should try to take steps to avoid it.” Such a test may be on the way. A study, presented at the Alzheimer’s Association International Conference 2019 found that the presence of certain bodies in the blood was highly associated with the development of AD about four years before the emergence of symptoms. The study was conducted by the National Institute of Aging in Baltimore, and it studied a group of 128 individuals who had eventually developed AD and 222 age- and sex-matched controls who had remained cognitively normal. Blood samples had been collected from these persons at the start of the study, and the median time from the collection of the samples to the onset of AD was 4.07 years. The specific bodies in the blood that predicted AD were extracellular particles, shed by all cells. The finding was that the diameters of the phosphorylated tau and phosphorylated insulin receptor substrate particles were significantly higher in the preclinical samples of individuals who would eventually develop Alzheimer’s disease than in those who did not develop AD. The differences between the test results in the group that developed AD and the group that did not indicated that the test would have a high degree of sensitivity (81.8%) and specificity (85.8%). The total area under the curve, indicating overall predictive efficacy, was 89.6% The lead researcher, Dimitrios Kapogiannis MD, notes that these results, while highly encouraging, are by no means the end of the journey. Kapogiannis pointed out that there are several other particles that may also be specific markers for AD, and it may be possible to add some of these to the assay and arrive at a test that is more accurate than the sum of its parts. (Kalogiannis D. JAMA Neurol 2019 Jul 15) A possibly relevant finding in this study was that the two cohorts had similar quantities of other substrate particles which were similar in diameter as well. One of the substrate particles that were similar both in quantity and diameter were Aβ 42, which is the form of Aβ that has been postulated as a causative factor in Alzheimer’s disease. But the study found no differences between the quantities or diameters of those particular particles between the individuals who went on to develop AD and those who remained free of AD. The study authors came to no conclusions regarding this finding and the question of Aβ as the underlying cause of AD. Nor did they suggest that their findings provided support for the alternative theory, that the true cause of AD is related to tau proteins. In any case, it is one more bit of evidence that needs to be considered in establishing the cause of AD. Other bits of evidence that need to be weighed include the continuing series of failures in the trials of keenly anticipated Alzheimer’s drugs of the class known as BACE inhibitors. What does the failure of BACE inhibitors say about the amyloid beta 42 hypothesis? We now know that our brains normally contain considerable quantities of a substance called amyloid precursor protein (APP). It is not inside the neurons, nor yet in the dendrites extending from the neuron, but in the spaces between the dendrites, across which the signal from one neuron is transmitted to another neuron. The signal is in the form of a neurotransmitter, usually a chemical that passes through the dendrite, across the synapse, is received by another dendrite, and travels to a receptor neuron. Our brains contain billions of neurons; each neuron can have as many as hundreds of thousands of dendrites, and the total number of synapses in our brains is thought to be in the neighborhood of a hundred trillion. And in all of those synapses there is amyloid precursor protein, a portion of which contains the amyloid beta peptide sequence. This is true of all normal, well-functioning synapses. What happens in the formation of the particular toxic plaques that result in AD is that enzymes cleave APP, leaving the amyloid beta (Aβ) segments. Two protease enzymes take part in this process – beta (β) secretase and gamma (γ) secretase. β-secretase (BACE) does the bulk of the work, and γ-secretase applies the finishing touches. It now appears that there are two versions of Aβ. One is a sequence of 40 amino acids; the other one is just two amino acids longer. These are now labeled Aβ 40 and Aβ 42. The ratio of Aβ 40 to Aβ 42 in plaque is usually about 9 to 1, but there is evidence suggesting that when the proportion of Aβ 42 increases, the toxicity of the plaque increases. Increased quantities of the Aβ 42 peptide appear to shift the behavior of the entire Aβ pool towards obstruction the transmission of information across synapses – in other words, towards dementia. A class of agents that showed early promise, but has since been disappointing, targets BACE, the enzyme that cleaves amyloid precursor protein (APP), thus resulting in Aβ accumulation in the synaptic space between neurons, and inhibiting the transmittal of neurotransmitters across this space. Since the transmittal of neurotransmitters from one neuron to another essentially constitutes brain activity, Aβ accumulation preventing this activity has been considered to be, if not the, at least an, essential cause of AD. Several agents inhibiting the action of that enzyme have been in various stages of development for a number of years. Most of these agents are in a class called monoclonal antibodies (mAbs), and they are derived from various sources. Researchers identify antibodies that have emerged in response to various challenges, some in mice (murine) or other animals, some in humans. These antibodies are then cloned and produced in the laboratory. The process of creating mAbs is basically the same whether the antibodies are in response to an immune process, as in rheumatoid arthritis, to a cancer, or, in the case of AD, to the enzyme that does most of the work of cleaving Aβ from the precursor protein. The news about these agents has been mostly bad: - Solanezumab, from Eli Lilly, failed to meet its primary end-points in terms of cognition and activities of daily living in a Phase III trial. - Bapineuzumab, from Johnson & Johnson/Pfizer, was supposedly scrapped three years ago, for a similar Phase III trial failure. Although brain imaging showed positive changes in Aβ deposition, the patients taking bapineuzumab did not demonstrate clinical improvement in cognition and activities of daily living. - Ganterenumab, from Roche, has also been scrapped, or at least interrupted. Ganterenumab is hampered by the risk of an adverse effect known as ARIA (amyloid-related imaging abnormalities), which can lead to dangerous swelling of the brain, thus there is a reluctance to push the dose, and effective dosing levels may not have been reached in clinical trials. - Crenezumab, from Genentech/Roche in partnership with AC Immune, also failed to meet endpoints in a Phase II trial, but reported some improvement in cognition in patients with mild AD. The most recent BACE inhibitor flops were particularly resounding. Merck’s verubecestat demonstrated a significant reduction in the levels of Aβ in the brain of patients with early Alzheimer’s, but this reduction was not accompanied by any beneficial effect on cognition. The Phase III trial compared two groups of patients taking 12 mg and 40 mg of verubecestat with patients taking placebo. At the end of 104 weeks of treatment, both groups of patient taking verubecestat had worse scores on tests evaluating cognition than did patients taking placebo. The test used was the Clinical Dementia Rating Scale-Sum of Boxes scores, with higher scores indicating worse cognition and daily function. The mean scores in placebo patients was 1.58, while the 12 mg and 40 mg verubecestat patients’ means scores were 1.65 and 2.02 respectively, suggesting not only that verubecestat treatment worsened cognition, but that higher doses worsened cognition more than lower doses. Looking at the estimated rate of progression leading to dementia, again the number of events considerably favored the placebo group, with an estimated 19.3 events per hundred patient years, compared with 24.5 and 25.5 events leading to dementia in the 12 mg and 40 mg verubecestat cohorts. A Phase 2b/3 trial in another BACE inhibitor, atabecestat, from Janssen, was terminated because participants taking the study drug had seriously elevated levels of liver enzymes. Interim scores of the Preclinical Alzheimer’s Cognitive Composite Score also suggested greater cognitive decline in the atabecestat cohort than in subjects taking placebo. A major setback in the BACE inhibitor arena was the suspension of two clinical trials in the drug aducanumab. In March of this year Biogen and Eisai announced that they would end the Phase III ENGAGE and EMERGE trials of aducanumab in early AD. An analysis demonstrated that the two trials had no chance of meeting their primary endpoints, those being the slowing of cognitive decline as measured by the abovementioned Clinical Dementia Rating Scale-Sum of Boxes. A total of 3,200 patients had been recruited worldwide for these trials. Workers in the Alzheimer’s field were disappointed, but perhaps not surprised. John Hardy, of University College in London, wrote “This tells us that the removal of amyloid in people with disease is too late. Amyloid is a disease trigger Once the neurodegenerative disease process is up and running, it’s up and running.” David Holzman, of Washington University, St Louis wrote, “I think Aβ is still a good target for the primary and maybe secondary prevention trials of AD, before tau and inflammation have started driving the disease.” These flubs do not mean that the strategy of preventing or slowing Aβ accumulation is a failure. However, a problem with the entire mAb class is the difficulty these molecules have in passing the blood-brain barrier. For example, the crenezumab molecule is huge – it consists of about 20,000 atomic units, with a weight of 144.88 kiloDaltons. As a result, the concentration of the antibodies within the brain is only about 0.1% of the concentration in the serum – or, to put it another way, to get enough concentration in the brain, the serum concentration has to be about 1000 times higher. This invariably entails a risk of adverse effects, so researchers are understandably highly reluctant to escalate the dose. No one at this point can be certain that beta-secretase does not play significant roles elsewhere in the body, so huge doses of any BACE inhibitor may be chancy. The failure of the Aβ-targeted therapies by itself does not mean that the amyloid hypothesis is null and void. However, it is by now clear that attempting to reduce the formation of more Aβ plaque, once the disease process is under way, will not have any clinical effect. What about taking aim at tau protein? Much less capital has been expended on this alternative hypothesis. The essential difference between Aβ and tau protein is that while the Aβ structures impede communication between neurons by congregating in the synapses, tau protein fibrils cause neuron death by forming tangles in the axons, which are the conduits through which neurons obtain nourishment. In brief, Aβ does its dirty work outside the neurons while tau protein kills neurons from within. A leader in the search for an agent that prevents or at least slows tau protein aggregation is TauRX Therapeutics, Ltd, of Aberdeen, Scotland. TauRX is a biotech spun off from the University of Aberdeen in Scotland, where its clinical trials are being conducted, although its official headquarters are based in Singapore, likely for tax reasons. Their AD candidates are derived from a parent compound, methylene blue, which has been around for decades, and has been used to treat malaria and methemoglobinemia, a blood disease in which normal hemoglobin is replaced by a form containing ferric rather than ferrous iron, which is less able to transport oxygen. TauRX’s first formulation based on methylene blue (methylthioninium chloride) was Rember, which has been replaced by a successor, LMTX, formerly labelled TRx0237. LMTX and Rember have the same mode of action, but LMTX is a stabilized, reduced form of the parent compound in order to improve the drug’s absorption, bioavailability, and tolerability. LMTX has been evaluated in a number of clinical trials and at several different dosages. In several of these trials, LMTX failed to meet its endpoints. However, in trials designated as TRx-015 and TRx-005, further analysis of the results demonstrated that patients who were taking LMTX as monotherapy experienced a significant decrease in disease progression in comparison with placebo, and the level of brain atrophy diminished by 33% and 38% respectively in the two trials. Both trials also determined that the benefit of the 8mg/day dose, originally intended to be a control, was similar to the higher doses and had fewer side effects. To confirm whether there is a benefit to LMTX as a monotherapy, TauRx is currently running another Phase II/III trial called LUCIDITY to investigate two low doses (8 mg and 16mg) of LMTX vs. placebo. The trial is looking to recruit 375 participants with early Alzheimer’s disease. The primary outcomes of the study include changes in brain function using imaging techniques, changes in cognitive performance, and the number and types of adverse events. Results of the study are expected in December 2020. What factors increase or decrease the chances of developing AD and dementia? An important point of departure is that Alzheimer’s is not synonymous with dementia. The type of dementia associated with AD is different from other types of dementia, as in dementia resulting from trauma or a cerebrovascular incident. The physiologic features of AD, such as depositions of the notorious amyloid beta and tau protein, do not result in dementia in every case. Persons with these elements in their brain frequently demonstrate characteristics of dementia, but not invariably. In a previous Doc Gumshoe piece about AD, I described a famous study in nuns, which found a strong link between the language they used in the essays they wrote when they first entered the nunnery and the likelihood of becoming demented in their later years. The analysis was not highly sophisticated. It simply measured the length of words and sentences. The nuns whose essays, composed for the most part when they were in their early twenties, employed longer words and sentences, were less likely to present symptoms of dementia fifty or sixty years later. The nuns in this study had also given permission to have their brains examined on autopsy, and it was found that many nuns who had many of the physiologic features of dementia in their brains, finished their lives in a totally lucid state. What presumably protected those nuns who, while having the Aβ deposits in their brains associated with AD, did not become demented, was what might be termed “cognitive reserve.” This sounds fairly obvious – if you have more reserve of any faculty, including cognition, you can afford to spare more of that faculty than a person that has less of it to start out with. And the data seem to support this concept. For example, several factors may affect cognitive reserve, either positively or negatively. Early life education and later life cognitive training boost cognitive reserve, while peripheral hearing loss diminishes cognitive reserve because of the lack of stimulating input that persons with hearing loss experience. An organization in the UK called the Dementia Prevention, Intervention, and Care Commission conducted an extensive observational study in about 10,000 community-dwelling adults. A conclusion of the study was that as much as 35% of the incidence of dementia could be attributed to what they called “Population Attributable Factors” (PAFs). The PAFs are risk factors that are subject to modification. The Lancet paper separates those modifiable risk factors according to periods in an individual’s life. In early life, poor education (i.e., no schooling beyond 11th grade) may account for 8% of dementia incidence, while in the middle years, the principal PAFs are hearing loss (9%), hypertension (2%) and obesity (1%), and in late life the PAFs are smoking (5%), depression (4%), physical inactivity (3%), social isolation (2%), and diabetes (1%). It’s highly likely that a number of those risk factors overlap; for example, high-school dropouts are far more likely to be smokers than are college graduates, and hypertension, obesity, physical inactivity, and diabetes certainly do tend to go together. Other data, by the way, tend to corroborate the Lancet conclusions, e.g., a 19% increase in midlife obesity in China was accompanied by a similar increase in the incidence of dementia. Cause and effect? Coincidence? Possible effect of dietary changes on dementia and Alzheimer’s In the Lancet paper adherence to the Mediterranean diet is suggested as a way of reducing the risk of AD and dementia. The Mediterranean diet is generally considered to be beneficial in the management of diabetes, hypertension, and elevated cholesterol, and there is evidence that this diet is beneficial in terms of prevention of the brain changes that are thought to lead to AD. However, there is no evidence for a comprehensive diet to prevent AD. Perhaps the strongest evidence relates to some antioxidant nutrients, including in particular vitamin E and vitamin C, which have been shown, at least in animal studies, to protect the brain from damage due to inflammatory and oxidative mechanisms. Three prospective human studies assessed the relationship between those nutrients and the risk of Alzheimer’s disease – one in Chicago, one in Rotterdam, and one in New York City. The Chicago and Rotterdam studies found a significantly lower risk of AD in individuals with a higher intake of vitamin E; the New York study did not find that association, but it happened that the vitamin E intake in subjects in the New York study was very much lower than in the Chicago or Rotterdam cohorts, so that may have accounted for the difference. The relationship between vitamin C intake and AD was much less robust than with vitamin E; only the Rotterdam study found a link. But none of those studies found a link between vitamin E and vitamin C supplements and a reduced risk of Alzheimer’s. To the extent that a reduced risk was detected in relationship with vitamin E intake, it was only as a result of the presence in the diet of foods that were rich in vitamin E. Which foods are these? According to nutritionists, the foods richest in vitamin E are vegetable oils, nuts (especially almonds), seeds, and also whole grains, eggs, and some fruits and vegetables such as avocados, apples, and melons. Doesn’t sound too bad. Dietary fats, especially transfats, may significantly increase the risk of Alzheimer’s. It’s intuitively attractive that cholesterol in the vascular system in the brain cannot be good for cognition, and a study in Japan showed a strong relationship between cholesterol levels and the deposition of amyloid plaques in the brain. The study followed 147 adults for up to 15 years before their deaths, and then performed autopsies on their brains. Those whose total cholesterol levels were more than 224 mg/dL were seven times more likely to have amyloid plaques than those whose total cholesterol was below 173 mg/dl. The link between elevated LDL-cholesterol, greater than 155 mg/dL and amyloid plaque was even more robust, by a factor of eight, over those whose LDL-C level was below 106 mg/dL. Whether those persons with more amyloid plaques were also actually more demented is not known. Other factors that affect cognition and dementia An investigation conducted as part of the Harvard Aging Brain Study found that greater physical activity was associated with slower Aβ-linked cognitive decline. The physical activity of 182 clinically normal adults, average age about 73 was monitored at baseline using waistband pedometers. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite for about 6 years. There was no association of physical activity with Aβ burden, but even modest levels of physical activity were linked to slower cognitive decline as well as grey matter volume loss. In both cases, the relationship was highly significant – P < 0.001 and P < 0.002. (JAMA Neurol. July 16, 2019. doi:10.1001/jamaneurol.2019.1879) Traumatic brain injury increases the risk of Alzheimer’s disease, and in some cases markedly ups the risk. A moderate brain injury doubles AD risk; a severe brain injury quadruples it. Trauma resulting in loss of consciousness for 30 minutes or more is classified as moderate; however, repetitive injuries resulting in shorter blackouts can have the same consequences for developing Alzheimer’s-related dementia. The most common cause is auto accidents, but football and boxing can lead to dementia. We haven’t gotten around to discussing the relationship between AD and the apolipoprotein genes – APOEε2, APOEε3, and APOEε4. APOEε2 is present in about 19% to 20% of the population, and those lucky folks have a lower incidence of AD, APOEε3 is the most common form and as far as is presently known, has no effect on the incidence of AD. APOEε4, on the other hand, is thought to be a culprit in AD. Up to 65% of persons with AD have at least one copy of APOEε4. It appears that having that gene doubles the likelihood of developing AD and perhaps even triples it. Persons with two copies of that gene – one from each parent – tend to develop full-fledged Alzheimer’s dementia at a much younger age than persons with one copy. Where do we come out? As we review the factors that seem to contribute to Alzheimer’s and AD dementia, a profile of the likely victim takes shape. She (most likely a woman) is poorly educated (a high-school dropout), obese, a smoker, eats mostly junk food, is physically inactive, and perhaps is afflicted with one or more chronic conditions such as diabetes, high cholesterol or hypertension – conditions which, of course, are more prevalent in obese sedentary smokers. Our victim is also more likely to be African-American or Hispanic. She might be able to improve her chances of avoiding Alzheimer’s dementia if she lost weight, quit smoking, joined a gym, and so forth. But that’s a lot harder than it sounds. In contrast, consider a very good friend of ours, who is highly educated, trim and fit, a life-long non-smoker who successfully manages his type 2 diabetes through diet alone. Nonetheless, he has Alzheimer’s disease, likely due to his genetic inheritance. He remains highly active and able to participate in conversations, which he ably steers to avoid the gaps in his cognition. He is receiving one of the very few drugs approved for AD – there are five in all, including one combination, and none of them make any pretense at reversing the disease course or doing anything more than perhaps slowing progression. I can’t think of a single thing that our friend could have done to prevent the development of AD. There will certainly be individuals like our friend, who, despite all efforts to the contrary including mental and physical exercises and the healthiest possible lifestyle, ultimately go on to develop Alzheimer’s disease. But they can probably stave it off and gain more years of living while in full possession of their wits. In fact, that’s the situation for the rest of us. What we want is for our mental capacities to remain optimal even as our physical capacities dwindle But what AD research tells us is that, at least in the case of Alzheimer’s disease, physical and mental capacities are one and the same. The transmission of information between our brain cells is purely physical, and it is that transmission that constitutes mental activity. Alzheimer’s impedes that transmission, likely through the growth of some form of crud in our brains. And because the growth of that crud is physical, there is reason to hope that some form of physical intervention, whether it be a drug (a chemical) or some form of exterior stimulation acting on the physical brain activity, may be able to counteract in some way the effects of the stuff that gums up the works in our brains. So in spite of the big decline in research aimed at finding effective new treatments, I (speaking as Doc Gumshoe) am keeping up my hopes for something that really works. * * * * * * * Thanks to all Planet Gumshoe denizens for reading this lengthy manifesto and for whatever questions / comments you send my way. Let me know what you want to read about and I will try to oblige. Best to all, Michael Jorrin (aka Doc Gumshoe)

Biomedical Research and Healthcare

9

Below is an investigative article that appeared in the Dutch on-line magazine De Correspondent. The original Dutch article can be read at the above link and a translation to English is given below. The translator included some comments or notes in brackets in the text. The Dutch pharmaceutical company Organon left crucial data that pointed at increased health risks out of their research findings of birth control product Nuvaring. Also, the company did everything [possible] to minimize the risks of thrombosis in the ‘enclosed’ [= the pamphlet accompanying the product, I’ll use ‘label’ from here on, also shows up as ‘product insert’]. This shows up in the documents in possession of ‘De Correspondent’ [this blog] From guest [blogger] Lucien Hordijk. Correspondent Technologie & Surveillance How health risks of the NuvaRing disappeared from the graphs Fall 2000. The American Federal Drug Administration had the task to judge a new birth control method of Dutch manufacture. The FDA had to judge if the NuvaRing, the revolutionary anti conception method by pharmaceutical company Organon [Brabant, province of NL, Oss, name of town] will be allowed access to the US market. The NuvaRing is a plastic ring, applied vaginally as opposed to pills, secreting for three weeks a ‘stable’, ‘low’ dose of hormones. Easier than a daily tablet, at least as effective in preventing pregnancy and insertable by the women themselves. The most important advantage: the low quantity of hormones, keeping side effects to a minimum. But precisely at the world’s greatest drug authority serious doubts arose about possible side effects of the NuvaRing. One of the medical researchers of the FDA, Daniel Davis, estimates that the number of thrombosis events in a few small-scale samples are twice as high as is known from pills with the same hormones already on the market. In comparison with anti-conception pills considered at that time as the safest, the chance [of thrombosis] is even four times as high. It is clear, writes Davis in an internal evaluation that, if we approve this new product, we have to point out the higher risks than those associated [normally] with these [same] hormones in the scientific literature. From documents in possession of ‘The Correspondent’, it appears that in the background a robust discussion has taken place between the FDA and Organon, that crucial data associated with increased risks of the product were left out of trial data and that the Company [Organon] successfully lobbied to keep the objections of the FDA out of the label. Because if the label emphatically warns for an increased risk of thrombosis, entry into the market would have been dead on arrival. Doubts of the FDA caused turmoil at Organon, as the company from Oss at that point already had invested ten years in this anti-conception product, specifically to be safer and easier than the pills, used as comparison by the FDA for the ring. The pharmaceutical has all reasons to get a favorable indication [literally ‘manual’] and rigidly maintains their position in the negociations about the wording on the label. The benefit of doubt The FDA decides, after months of bickering, to overlook a few young victims of thrombosis during the drug trials. Instead of mentioning the doubts of the FDA about the hormones, the final label notes that it is unknown if the increased chances with pills regarding thrombosis are also valid for the NuvaRing. The anti-conception ring is current used by 1.5 million women yearly. Dutch and US employees of the ‘Regulatory Affairs’ division of Organon are satisfied when the hard fought business license is ‘pulled out of the fire’, documents show. The anti-conception ring, the first of its kind, is ready to conquer the world. And a conquest it became. The anti-conception ring is used these days by 1.5 million women yearly and yielded MSD, the current manufacturer of the NuvaRing, 686 million dollar in 2013. According to MSD 179 million units were sold in the initial 10 years and it is meanwhile available in fifty countries. In the Netherlands the ring is provided 170 thousand times. Lobbying to keep information ‘indoors’ [restricted] But this commercial success has another side. Past June, the manufacturer concluded a lawsuit before the US high court [they use this term], where they were sued by thousands of users and next of kin because of the systematic withholding of information. Information that would point at health risks such as thrombosis, embolism and cerebral infarction. The result of the indictment is a settlement of $100 million, accepted by 95% of the approximately 3,800 plaintiffs. In return, MSD was found not guilty of withholding information that would inform users and prescribers of the ring of the higher risks of thrombosis and embolism as compared to other anti-conception products. After a ‘muscled’ publication, ‘De Tegel-genomineerde publicatie van Anneke Stoffelen’ in the ‘Volkskrant’ [=a Dutch paper] of November last year about this lawsuit, a short discussion took place in the Netherlands about the NuvaRing. The Volkskrant article explored the doubling of the risk of blood clots of the NuvaRing compared to older anti-conception products. The ring would be just as risky as the Diane-35 pill, an anti-conception product that was withdrawn from the French market early 2013 because of the possibility that it caused the death of four young women. In the Netherlands, too, deaths were related to the use of the Diane-35 pill. MSD, in a press release, ‘considered the article as information’ and ‘stands completely behind the NuvaRing’. Henk Jan Out, ex vice-president Women’s Health of the company, sneered in a column in ‘Artsennet.nl’ [link supplied] that the Volkskrant article was a mouthpiece of the US tort lawyers. Caroline Doornebos, medical director at MSD, reacted during broadcasts of the NOS [=Dutch broadcast network] and Omroep Brabant ‘Het bericht’ van Omroep Brabant (local broadcaster) and assured ‘that there is no difference in risk of thrombosis from the NuvaRing as compared to other anti-conception products’. From the court documents of the US lawsuit, witness declarations and correspondence with lawyers and scientists, another picture emerges. MSD has tried to prohibit public access to these documents but were overruled by the judge. [‘anders’ is a link to the judgement: ‘the decision in this matter’]. The Dutch enterprise Organon received before, during and after market entry different signals that the Nuvaring certainly entails an increased risk of bloodclots compared to other anti-conception products, but did not undertake anything to publicize this. Even worse [lit. ‘even stronger’], Dutch employees lobbied effectively to keep this information ‘indoors’ [restricted]. Onto the market Before the NuvaRing was admitted to the market in the Netherlands as well in the US, a lot of discussions took place in the medical world about the hormones that would be used: ethinylestradiol, an estrogen, and etonogestrel, a so-called third generation progestogen. Already in the nineties a lot of scientists agreed: anti-conception products with third and fourth generation progestogens have twice the chance of causing life-threatening side effects such as thrombosis compared to products with second generation progestogen. Out of sixteen trials thirteen confirmed this link. Three pharmaceutical industry sponsored studies found no link. That the manufacturer selected the patented etonogestrel for the NuvaRing is a logical choice business-wise: the hormone is a chemical derivative of its predecessor desogestrel, as of 1995 no longer patented. Still, etonogestrel was marked by the drug authorities as a ‘new molecular entity’. For this reason, Organon hardly needed to supply new toxicological (animal and in-vitro) results. Also in the clinical phase of the research the company was allowed to refer to trials of the older products in the portfolio of Organon such as Marvelon and Mercilon. In short, Organon was allowed to patent in an attractive way a new (sort of) molecule for their unique anti-conception product. To convince the drug authorities about the effectiveness and safety of the product, nine studies were performed by Organon. These trials mostly took place in the Netherlands, with the participation of 2,586 women. The larger part of the studies investigated the effectiveness of the ring. One study was devoted to the way the hormones from NuvaRing were absorbed by the body. An essential study, since hormone levels that are too high are associated with a greater chance of side effects. The study, that should validate the reason for existence of the product, consisted of sixteen participants and was performed by two scientists from Organon. From the graphs and tables of this study, some of which also found their way onto the label, and in the publicized evaluation report of the ‘Dutch college for the evaluation of drugs’ [CBG], it shows that the average secretion of both hormones is stable. [lit.‘average release from both hormones with users stable happening’]. Good news for Organon. Bron: Onderzoek 34.218 van Organon. Text above graph: average hormone secretion of the NuvaRing. Bron: Expert Report of Shelley Ann Tischkau. But the visualizations [graphs and tables] are not a complete representation of what was found with the participants [of the study]. From two research reports, introduced as evidence during the in June settled court case, it appears that the data of at least four women were omitted from the graphs and tables. These reports show that two medical employees of Organon confirm this. Therefore the US label, the publication of the study, the evaluation report of the CBG and the concluding document submitted to the FDA by Organon in order to obtain a license did not show a complete picture of the results of the study. At four of the sixteen participants strong peaks of the hormone ethinylestradiol, a so called ‘burst effect’ took place. In two users the peak occurred a few hours after insertion of the ring, two other women experienced a surge of ethinylestradiol later on. Source: Expert Report of Shelley Ann Tischkau Above graph: the omitted peaks; burst effect with four women Tom Sam, at the time a biochemist at Organon, admitted in a testimony during the court case that these four peaks were not processed into the graphs and tables. One of the researchers of the trial confirmed that the physicians prescribing the NuvaRing for women never would know that a few ‘burst effects’ took place. The research data [lit. ‘little research’] that should show that the NuvaRing secretes hormones in an even manner, showed that the contrary was the case. In September 2001, when the FDA still had the application for NuvaRing under consideration, a worried Organon employee sent an e-mail to a colleague. It would be extremely damaging for the NuvaRing if the FDA were to be informed of the ‘burst effect’. He wrote: ‘Going to FDA to change these specifications is absolutely the LAST thing we should consider, i.e., that’s the worse[sic] possible scenario.’ ‘The Correspondent’ asked the Dutch drugs authority CBG if they were aware of the selective data use by the manufacturer in this specific research. The answer was that they could not possibly imagin that these data were omitted from the graphs. The authority [CBG] stated to get to the bottom of this now. The CBG does emphasize that the alleged clinical advantage of the anti-conception ring is not mentioned in the Dutch label. ‘We have from the outset pointed to an increased risk of thrombosis, similar to Marvelon. We expressly prohibited Organon to claim in the pamphlet that the hormone levels were better of more even than the daily peaks that would be apparent with pills [lit. ‘that you would see with pills’]. In other words: the manipulated research by Organon is also taken by the Dutch authority as guidance but considered too skimpy [lit. ‘skinny’] to endorse the conclusions. Manufacturer MSD, to this day, maintains the position that the ring has less side effects because of the low and even secretion of the hormones. In a reaction to an article in ‘De Volkskrant’ of November 2013, the company takes the position that ‘the hormones that prevent pregnancy are secreted evenly over a month. Even secretion means that no hormone peaks or valleys in the blood levels occur. Inasmuch that high levels can lead to side effects and low levels to insufficient effectiveness, striving for even blood levels is a very much accepted and logical starting point’. Illustrating the point: on the MSD website ‘Anticonceptie.nl’ under the header ‘anticonceptiering’ [anti conception ring], ‘voordelen’ [advantages, link provided], ‘hier te lezen’ , read here. ‘An even secretion of hormones: the anti conception ring has therefore no daily hormone peaks like the pill’ The summary document from the CBG of 2001 endorses this position. There can be read, among other things, that the ring effectively prevents pregnancies but that less side effects in comparison with pills are insufficiently indicated: ‘Additionally, any clinical advantage of an absence of daily peak concentrations of estrogens and progestogens, in terms of a more favourable adverse event pattern, remains to be established.’ Thrombosis occurrences expunged from the label Organon, during the registration procedure in the US, also did everything to get all unfavorable information out of the label. In the clinical studies for market entry, three young women were shortly after application of the NuvaRing diagnosed with variations of thrombosis. On this basis, the FDA concluded that the risk of thrombosis of the NuvaRing was twice the risk of anti conception pills with Desogestrel, known to have a risk of twice the second generation pills. ‘We should really try to get it out of the text’ Susan Allen, with final responsibility of the FDA department judging studies, pointed specifically to one of these cases of thrombosis. A 26 year old woman in the clinical study developed a deep vein thrombosis in her left leg eight days after application of the NuvaRing. It was for Allen a reason to order the manufacturer to emphasize in the pamphlet the increased risk of thrombosis of third and fourth generation progesterones, such as used in the ring. And more importantly, to specifically mention the thrombosis occurrence of the 26 year old. This way, physicians could judge for themselves if they wanted to prescribe a drug that was already associated with violent side effects in such a small research population. From internal correspondence between marketing department and registration procedure department employees in the US and the Netherlands, it appeared that this proposal by the FDA was not well received [lit:‘did not really fall on fertile ground’]. Wim Mens, at the time working in the department of Regulatory Affairs in Oss, reported to his colleagues that he worried greatly about the mention of this case of thrombosis on the label. He wrote: ‘We should really try to get it out of the text’. A marketing colleague in the US, David Stern, agreed. He suggested to use animal data from an earlier toxicological study as a trump card in the negotiations, to get the FDA to delete the ‘more important things’ such as the specific thrombosis case, deleted from the label. [this does not really make sense to me – but this is what it says here]. ‘A good thing’ Surprisingly, Organon prevailed. By refusing the proposals of the drug authorities, the company managed to delay the initial registration procedure, the documents show. The 26 year old woman disappeared from the pamphlet and the position became ‘that it is unknown if the increased chances of thrombosis associated with third generation anti-conception products are also valid for vaginal application of etonogestrel’. The label contained only a general warning for blood clotting. For Organon’s US marketing director this was still not enough, so he wrote to his colleagues: ‘The label change looks much better, however, I am still unhappy with the VTE section [Venous Thromboembolism, venous thrombus emboli, LH] of the label. Obviously the case that we presented to them [FDA, LH] has made some impact, in that they added the statement about being unknown if NuvaRing has this increased risk. What are the chances that this section can be removed all together?’ Retired team leader Willem de Boer, at the time team leader ‘Regulatory Affairs’ in Oss, was pleased by the finished label, which omitted the young woman with the deep artery thrombosis: ‘I have reviewed the new proposal for the NuvaRing Package Insert made by the FDA. To my satisfaction a number of critical issues have been implemented in the current proposal of the FDA (e.g. the deletion of the single VTE case).’ His US colleague Nancy Alexander also found the disappearance of the thromboses matter ‘a good thing’ An extra complaints department . Still, Organon would not be able to prevent forever that their anti-conception ring would not increasingly be associated with increased thrombosis risk. Immediately after obtaining a trade license the company started new studies. Between the end of 2001 and begin 2004, again three more deep vein thrombosis cases occurred in a clinical setting. Here, too, young women varying in age from 20 to 28 years were suffering side effects. In an interim report, generated by Dutch ex-employees, a VTE (Venous Thromboembolism) risk factor of 10.1 out of 10,000 women is calculated at that time. Five years after entering the market it appears after all that the anti-conception ring increases the risk for thrombosis. Organon started the same year with a ‘VTE issue team’, tasked with the sensitive matter. Inside Organon the fear exists for underreporting, the phenomenon that the number of thrombosis victims is many times higher than estimated on the basis of calculations. Also, the public at large starts to get worried about the side effects, witness the dramatic increase in patient’s questions regarding the chances of a thrombosis induced by the ring, as mentioned by a US director. Patients reporting side effects only will be acknowledged [lit. ‘called back’] after the judicial department has analyzed [lit. ‘x-rayed’] the report. Of all reported side effects for the complete drugs gamut of Organon, nine out of ten relate to the NuvaRing, according to an internal mail. Lacking capacity, an external entity is contracted to process the reports regarding the anti-conception ring. Winning from the patch The consternation of the users is, among other reasons, fueled by the action of the FDA a few months earlier. A direct competitor of the NuvaRing, the Evra anti conception patch manufactured by Johnson & Johnson, approved one month after the NuvaRing, gets end 2005 a review of the label and an infamous ‘black label box warning’. The patches, just like the rings, dispenses hormones in an alternative way and, according to the FDA, exposes women to a relatively high dosage of estrogen so consequently doubles the risk of dangerous side effects such as thrombosis. The ‘black label warning’ has disastrous effects on the sale of the patches in the US. Where the company still sold about five million patches in 2005, in 2011 this decreased to less than 1.5 million. The NuvaRing sales skyrocket in 2005 by about 50% to 2.5 million units sold. Organon is gets the chance to increase their sales at the expense of their main competitor but struggles internally with how to manage the matter of the thrombosis risk. Indeed, the patch touted the same stable hormone levels but still received an emphatic warning. Convenient for the marketing The pharmaceutical [Organon/MDA] obtains help from Susan Allen, the manager of the FDA who, five years earlier, wrestled with Organon about the thrombosis cases in the clinical studies. Under her leadership, the FDA not only approved the NuvaRing, but she also was instrumental in the Evra patch obtaining a license. Now she is making a living as an independent consultant for the pharmaceutical industry. In 2006 Allen met Dutch director Hans Rekers, at that moment Vice President of Medical Affiars at Organon. They ‘sit at the table’ to craft a ‘fitting communications strategy’ now that the company is increasingly faced with ‘spontaneous reports of side effects like thromboses’. The company decides to recruit the problems of their competitor by starting a marketing campaign touting the ‘advantages’ of the anti-conception ring over the maligned patch. A ‘dear doctor’ letter is crafted, in which the company informs physicians of the low estrogen exposure of the ring with respect to the patch. Also, a course for medical representatives is developed, training them to emphasize specifically the differences between the ring and the patch. Never a word about the increased risk of thrombosis, as is apparent from the testimony of a US Sales Director, Sue Iannone: ‘It’s not something you’re going to see in a sales aid or in a users guide, because that’s not what healthcare providers typically want to talk about with representatives. And that’s not how we promote the products […] because they are safe if it’s approved by the FDA and there is a label.’ Women should be empowered to make a choice. In a reaction of the company to questions of ‘The Correspondent’, MSD informs them [link supplied] ‘The questions of ‘The Correspondent and the answers of MSD’, that a substantial investigation is pending that will guarantee the safety of the product. The company points at the adaptations made worldwide to the ‘product inserts’, showing the results of both these researches that did not find a higher risk of thrombosis compared to second generation pills. [This is a really weird sentence: it mentions ‘pending investigation’, future tense, and than says the results of these pending investigations are known.]. However, one of these investigations according to a process document in the possession of ‘The Correspondent’ , does not have sufficient number of participants to give a decisive answer regarding the safety of the NuvaRing. A well known Danish study under leadership of the Danish professor Øjvind Lidegaard with more than 3 million participants, found a NuvaRing thrombosis risk factor that was double that of second generation anti conception products. This study is not taken seriously by MSD on grounds of the methodology. Lidegaard denounces the position of the manufacturer, which, according to him, has been trying for years to nip the discussion about the safety of the product in the bud: ‘There is strong scientific proof that the NuvaRing has at least twice the chances of causing thrombosis as compared to second generation pills’. Asked if he feels that the drug authorities have to warn about risks, the professor answers affirmative. ‘As long as women are not informed about the differences in risk of thrombosis between the various products, they are not in the position to make an informed choice’. Ironically, the manufacturer also considers adequate information for women fundamental. Only, the product insert of the NuvaRing does not mention, up to today, any study that flags the increased risks compared to the second generation pills. This article is written by guest correspondent Lucien Hordijk

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This week, The Wall Street Journal reported from TEDMED on an issue close to The Michael J. Fox Foundation’s heart: “Bridging the Gap Between Basic Research and Patient Care.” The Journal highlighted remarks from National Institutes of Health head Francis Collins, who provided colorful illustrations for how to accelerate translational research in drug development, as he called for the need to “build a bridge across this yawning gap” in order to bring novel drugs to the people that need them, faster. Imagining the gulf between basic science and applications as a body of water, Collins said linking them wouldn’t be like building the Golden Gate Bridge. Rather, it’s more like a swimmer, a sailboat and a tugboat all attempting to cross the water. There are sharks and other obstacles in the water, causing the swimmer to die, the sailboat to capsize and the tugboat to run aground. So how to navigate these treacherous waters? One way to do it, Collins said, would be for pharmaceutical companies to “open their drug freezers” and repurpose drugs that have been determined to be safe and potentially effective, to target diseases for which the drugs weren’t originally developed. Collins is talking about an idea called repositioning, and new this year, it’s become one of the Foundation’s recurring programs. Since the development of new drugs is expensive, and can take years to bring to market (the average for central nervous system therapies is somewhere between 10-20 years) the hope is that, by identifying therapies that are already clinically available, scientists could potentially lower the time and costs involved in finding drugs that could help people living with PD. Last year, MJFF funded nine awards totaling $3.4 million repositioning existing drugs that could benefit PD patients, at various stages along the pipeline. Pre-clinical studies to this end included one seeking to determine if the antidepressant duloxetine, also known as Cymbalta, can be used as neuroprotective therapy, and another testing a compound used to treat Attention Deficit Hyperactivity Disorder (ADHD) to determine whether it could enhance dopamine production as a form of symptomatic therapy. Read this article from BioTech Now to find out more about last year’s MJFF-funded grants in repositioning.

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Bioinformatics is conceptualizing Biology in terms of molecules (in the sense of Physical Chemistry) and applying “informatics techniques” (derived from disciplines such as applied mathematics, computer science and statistics) to understand and organize the information associated with these molecules, on a large scale. It explores new ways for approaching biological problems and aims at the comprehension of basic principles of Biology. Bioinformatics interacts strongly with modern structural, molecular and environmental biology, as well as with pharmaceutical and medicinal chemistry. Nowadays, the field is rapidly developing worldwide; several important goals have already been accomplished, while large investments from various sources are continuously attracted. Bioinformatics occupies a central position in the recent developments of Life Sciences, with the most sound example being the analysis of data derived from all genome sequencing efforts, including the Human Genome Project. Since 2003, the Faculty of Biology in the University of Athens organizes and operates the “Bioinformatics” Postgraduate Programme, in accordance with the provisions and articles of the Ministry of Education, Research and Religious Affairs (FEK 773/17-0-2003), under the direction of Professor Stavros Hamodrakas. Since 2014, the Programme operates in its updated form, in accordance with the articles of the Greek Laws 3685/2008 (FEK 148, No. A) and 3014/2014 and the ministry declaration No. 43800/B7, under the direction of Professor Constantinos Vorgias. The revised Regulations of Studies have been devised and approved by the Programme’s Coordinate Committee and the Faculty of Biology’s General Assembly. The Bioinformatics Postgraduate Programme aims to satisfy the need for high-quality training of young scientists, with the intention to enter the challenging field of Bioinformatics.Given the explosion in Biotechnology research (including, among others, Pharmacogenomics and Molecular Medicine), the emergence of a critical mass of scientists with a foundation in Bioinformatics, should lead to the advancement of modern biological research in our country, in both academia and industry. The Bioinformatics Postgraduate Programme is organized and coordinated by the Faculty of Biology of the National and Kapodistrian University of Athens. At the same time, the Programme collaborates with a number of prominent Universities and Research Institutions including the Agricultular University of Athens, the University of Thessaly, the National Technical University of Athens,. the Harokopio University, the Biomedical Research Foundation of the Academy of Athens (BRFAA), The National Hellenic Research Foundation (NHRF) and the National Centre for Scientific Research “Demokritos”. The Programme’s courses are taught by Professors and Researchers from the above institutions, as well as invited speakers from other institutions, both in Greece and abroad. The Programme is accommodated in the Department of Cell Biology and Biophysics, Faculty of Biology at the campus of the University of Athens. Prerequisites for Admission The Bioinformatics Postgraduate Programme admits graduates from Schools of Science, Polytechnic, Economical and Agricultural schools and Medical/Biomedical schools from recognized academic institutes, both in Greece and abroad, as well as graduates from Technical Educational Institutes (TEI) with related disciplines. Apart from the applicant’s Bachelor degree, the prerequisites for admission are defined by the Programme’s Coordinative Committee. The admissions process also includes a personalized interview for the applicant before the members of the Committee. A maximum of 20 students are accepted per year. Admitted graduate students will receive the same perks as undergraduate students of the University, as defined by the articles of the Law No. 2083/1992. The Programme’s curicullum is organized in four semersters (two academic years). The Programme’s costs are covered by the students’ tuition fees. Fees are set to 1500€ per year (a sum of 3000€ for two academic years). More information can be found in the Admissions Page.

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The annual Terry Fox Runs is days away, and our students are gearing up to raise money for cancer research and help keep Terry Fox’s dream alive. Terry Fox’s Marathon of Hope might have ended in 1980 but the spark he lit in the hearts and minds of Canadians ignited into a campaign of hope that has lasted more than three decades. Once again this September hundreds of thousands of Terry Fox supporters will participate in their favourite Canadian fall tradition at one of more than 700 Terry Fox Runs from coast to coast to coast to ensure that cancer research continues to forge ahead. The students and staff at the Near North District School Board appreciate your support with this important initiative. Terry Fox had a single dream: a world without cancer. Come and join us as we work together in pursuit of this dream. For more information on the Terry Fox Run and Foundation, visit www.terryfox.org

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Background Requirements based biopsychosocial problems instrument for cancers sufferers (CANDI) is a range based on requirements arising because of the effects of cancers. between CANDI and HADS (rs = 0.67), and BSI (rs = 0.69) and FACT-G (rs = -0.76) were average and significant in the expected path. Conclusions CANDI is normally a trusted and valid range in cancers sufferers using a buy GHRP-6 Acetate three-factor framework (psychological, physical and public) in the Turkish vocabulary. Keywords: Cancers, Psychological Stress, Require, Validity, Dependability 1. Background Cancer tumor sufferers are affected psychologically because of the results of both disease and the procedure received. Nervousness and unhappiness are mostly observed (1). The condition itself affects the life span buy GHRP-6 Acetate from the sufferers aswell as their own families. While the patients try to cope with disease-related physical, emotional, social and economic problems, many different needs arise, which lead to distress (2, 3). In consequence, this outcome in cancer patients is usually therefore regarded as a biopsychosocial distress. The biopsychosocial distress that emerges is usually described as an emotional state that troubles the patient and has behavioral, emotional, social, physical, psychological and economic components. A global approach toward cancer patients involving these different fields and specialties is regarded as more beneficial (4). The most important issue is the identification of problems and needs in the early diagnostic period and the provision of professional assistance (5). Many studies have investigated the stress, depressive disorder, lower quality of life and psychosocial distress that occur in cancer patients (6-9). Differently, Lowery et al. (4) developed the needs based biopsychosocial distress instrument for cancer patients (CANDI), which is a scale based on needs arising due to the effects of the disease, depending on a global approach. Being based on needs, they aimed to address different facets of having malignancy that are apparently experienced by the patients throughout the phases of cancer. This scale differs from other scales in being directly concerned with daily life and involving a problem-focused approach. In terms of its structural characteristics, it is intended to address the entire biopsychosocial field and to do this on the basis of emotional, physical, interpersonal and economic requires arising in patients lives. Another advantage is that it can be applied under clinical buy GHRP-6 Acetate conditions. 2. Objectives The purpose of this research was to determine the reliability and validity of the CANDI scale in Turkish and to assess its usability in Turkish-speaking cancer patients. 3. Patients and Methods 3.1. Ethical Considerations This methodological research was carried out between January and April, 2014, at the Karadeniz technical university (KTU) medical faculty oncology clinic chemotherapy unit. The research was approved by the KTU medical faculty clinical research ethical committee (2013/120-677). 3.2. Participants The research was performed with the participation buy GHRP-6 Acetate of patients aged 18 or over, receiving chemotherapy on an outpatient basis and actually and psychologically healthy enough to understand and complete the consent form. The participants were chosen from voluntary patients. The research sample was computed using the G*Power 3.1.5 program with alpha = 0.05, power = 95% and effect size = 0.25 with the participation of at least 200 cancer patients, and was eventually completed with the participation of 201 patients (10). The patients who had unanswered questions in the CANDI were excluded (n = 29). 3.3. Steps The CANDI scale consists buy GHRP-6 Acetate of five subscales emotional state (stress and depressive disorder subscales), social state, physical condition, health care and practical life and is based on 39 questions completed by patients marking the options most appropriate to themselves. These subscales were formed conceptually. The scale was drawn up by Lowery et al. (4), and its validity and reliability in American society have been confirmed. 3.4. Scoring Item scores were summed to create a total CANDI score (4). All of the patients who had responses of Prefer not to answer and Do not know were excluded from the study (n = 29). Subscales for depressive disorder (four items) and stress (two items) were calculated in the Rabbit polyclonal to GNMT same way. The hospital stress depressive disorder scale (HADS) and brief symptom inventory (BSI) were used to determine convergent validity, and the Fact-G scale was used to determine divergent validity. HADS was developed by Zigmond et al., consists of 14 questions and is used to measure stress and depressive disorder. The validity and reliability of the Turkish-language version were established by Aydemir et al. (11-12). Cut-off points of.

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By means of Ellie Quinlan Houghtaling HealthDay Reporter FRIDAY, July 22, 2022 (HealthDay Information) You need to communicate to children about circle of relatives well being dangers, however the affect of sharing this sort of knowledge has been unclear. It is most probably protected, in keeping with a brand new find out about, however how are you intended to do it — and when? Researchers discovered that youngsters most often don’t have any drawback coping when most cancers chance knowledge is shared with them. However it isn’t unusual for fogeys to combat with speaking the scoop. “We incessantly inform folks every so often conversations occur whilst you least be expecting them, like in a automotive trip to a carrying match or a circle of relatives accumulating,” stated find out about co-author Beth Peshkin, director of genetic counseling at Georgetown College’s Lombardi Complete Most cancers Middle in Washington, D.C. There also are herbal alternatives to discuss those critical problems — as an example, across the time of Mother’s annual mammogram. Because of this, you must ask your self the large questions forward of time. “When do you notice your self sharing this information? How would you are feeling in case your child requested or came upon about it round you?” Peshkin stated, including that you must believe a kid’s psychological construction and to make a decision whether or not and what to percentage on a case-by-case foundation. “Specifically with more youthful children, give them a bit of bit and spot if they would like extra,” she stated. This find out about incorporated 272 teenagers and younger adults — 76.1% had a mom who had survived breast or ovarian most cancers, and 17.3% had moms who examined certain for the BRCA gene, striking them in peril for the ones two cancers. After studying about their moms’ BRCA standing, younger other people reported fairly low ranges of mental pressure. “To me the most important takeaway is that wisdom and knowledge is energy,” stated Kelsey Largen, a medical pediatric psychologist whose paintings specializes in most cancers and blood issues at Hassenfeld Youngsters’s Health facility at NYU Langone in New York Town. “By means of studying this data about their folks, those kids then have the ability to make adjustments to their way of life of get ready for a problem forward. I believe that is all the time really useful,” stated Largen, who wasn’t concerned with the analysis. However the find out about, printed July 21 in Pediatrics, additionally discovered that even if children have been offered with this data, it wasn’t prone to alternate their habits. Wisdom in regards to the most cancers chance did not prevent them from smoking and did not suggested them to drink much less or workout extra. “The takeaway for us was once that even supposing we did not see total adjustments in what children have been doing when it got here to smoking, alcohol use or workout, that there was once consciousness,” Peshkin stated. “I believe that is key to capitalizing in this. Possibly they were not given any equipment or any formal option to discover the way to get to the bottom of this.” Whilst extra analysis is wanted, transparent pathways to do so after the scoop is published is usually a option to alternate long term habits. “If I have been chatting with a tender grownup whose mother or father discovered they have got this mutation, I’d have a look at it when it comes to coping. To mention, ‘You would not have this [illness] at the moment, however for those who have been to stand this, there are assets to be had to you if this must occur someday. We will be able to discuss how you’ll be able to use those coping abilities to care for demanding situations as they get up,'” Largen stated. “As a psychologist that is what I’d consider,” she stated. “How are they dealing with the scoop? How are we able to lend a hand them get ready emotionally?” However in the long run, it is a excellent signal that youngsters are resilient and in a position to deal with necessary knowledge. Oldsters should not keep away from it or alternatives to speak — children will likely be OK. “We are incessantly seeking to persuade folks to percentage knowledge with their kid on the subject of most cancers, as a result of we all know the additional info [the kids] have the simpler they cope,” Largen stated. The American Most cancers Society has extra about most cancers dangers. SOURCES: Beth Peshkin, MS, CGC, director, most cancers genetic counseling, Georgetown College, Lombardi Complete Most cancers Middle, Washington, D.C.; Kelsey

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Devices such as hard drives, CDs, and DVDs provide storage for nearly all of the world’s information, but less is known about the storage potential of biological materials. Researchers at the Yale Systems Biology Institute have found that it is possible to store information in the protein polymer network - or “actin cytoskeleton” - that forms the mechanical scaffolding within our cells, and which is responsible for maintaining and changing cell shape. Published in the journal Advanced Functional Materials, the scholars describe the organizational role of a seed-like nucleator called ‘formin’ in controlling the rate of assembly of the polymer network. By tuning the density of the seeds and their rate of network assembly, the scientists were able to control the architecture and shape of the actin polymer network, effectively like encoding new biological memory. Advancing our understanding of polymer mechanics opens the way for biological principles to be used in future memory storage devises. The lead author of the article is Vikrant Yadav, a postdoctoral fellow in the lab of senior author Michael Murrell, assistant professor of biomedical engineering and physics. The work is a collaboration with scientists at University College London, the University of Chicago and Purdue University, and is funded by the Department of the Army and the Human Frontiers Science Program. By Jon Atherton

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The treatment of cardiac arrest has made significant progress over the last 10–15 years. This period marks a significant turning point, because the treatment of out-of-hospital cardiac arrest (OHCA) had often been considered an exercise in futility, with no improvement in outcome for the previous 30 years (Berdowski et al. 2010). In recent years, several investigators have documented marked improvements in survival after OHCA, particularly in those cases with an initial shockable rhythm (ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) (Wissenberg et al. 2013; Daya et al. 2015; Chan et al. 2014). Several interventions are likely responsible for the improving survival rates following OHCA. Bystander cardiopulmonary resuscitation (CPR) is associated with survival rates that are 2–3 times higher than those cases without bystander CPR (Hasselqvist-Ax et al. 2015; Rajan et al. 2016). Emergency medical services dispatchers are now better trained to efficiently ask the right questions to enable prompt recognition of cardiac arrest and then to instruct the caller to perform compressiononly CPR (telephone CPR) (Bobrow et al. 2016). For shockable rhythms, reducing the delay to attempted defibrillation also improves outcome. Implementation of public access defibrillation (PAD) programs and dispatch of community first responders trained to use automated external defibrillators (AEDs) will reduce the time to defibrillation (Blom et al. 2014). Text alerts can be used to direct first responders to retrieve the nearest AED and then take it to the scene of a cardiac arrest (Zijlstra et al. 2014). Once return of spontaneous circulation (ROSC) has been achieved, post-resuscitation management impacts significantly on the ultimate neurological outcome. European guidelines for the management of postcardiac arrest patients were published in 2015 and describe the interventions that will optimise outcome (Nolan et al. 2015). Those patients who achieve ROSC and have ST-elevation (STE) on their ECG will require urgent coronary catheterisation because most of these will benefit from percutaneous coronary intervention (PCI) to restore coronary perfusion (Dumas et al. 2010). The immediate management of those without an obvious non-cardiac cause and without STE is controversial. Some experts advocate urgent coronary catheterisation in all such patients (Dumas et al. 2016). Current European guidance is that these patients should also be discussed with interventional cardiologists and considered for urgent coronary catheterisation (Nolan et al. 2015). Some centres will immediately catheterise cardiac arrest survivors without STE, but only if they had presented with a shockable rhythm. Cerebral autoregulation is disturbed in 35% of post-cardiac arrest patients and is particularly associated with pre-arrest hypertension (Ameloot et al. 2015a). The optimal target mean arterial pressure (MAP) post cardiac arrest is likely to vary between patients, but to avoid secondary brain ischaemia it has been suggested that the optimal MAP is likely to be in the range 85–105 mmHg, which is somewhat higher than the 65–70 mmHg that is widely used (Ameloot et al. 2015b). Until recently, in the immediate period after ROSC (certainly prehospital and often in the emergency department) it has been common practice to ventilate the lungs of comatose post-cardiac arrest patients with 100% oxygen. This not unreasonably reflected concerns about harm from hypoxaemia and lack of awareness of harm from highconcentration oxygen. Animal studies have documented worse neurological outcome from the use of 100% oxygen immediately after ROSC, particularly during the first hour (Balan et al. 2006), and some observational studies using data from intensive care unit (ICU) registries have documented an association between hyperoxaemia and worse outcome among post-cardiac arrest patients. In a randomised controlled trial (RCT) the use of routine supplemental oxygen among patients with STE myocardial infarction (but not cardiac arrest), resulted in an increase in size of myocardial infarction compared with patients given oxygen only if hypoxaemic (Stub et al. 2015). A RCT of oxygen titrated to 90–94% versus 98–100% as soon as possible after ROSC and continued until ICU admission (EXACT phase 3 trial) will inform the optimal oxygenation strategy after ROSC (Nolan et al 2017). European guidelines recommend the use of a protective lung ventilation strategy in post-cardiac arrest patients, but this was based mainly on data extrapolated from patients with acute respiratory distress syndrome (Nolan et al. 2015). However, a recent observational study of OHCA patients using propensity matching has documented an association between the use of time-weighted average tidal volumes of < 8 mL kg-1 predicted body weight and better neurological outcome (Beitler et al. 2017). Mild hypercapnia may also be associated with better neurological outcome in post-cardiac arrest patients, possibly because it may increase blood flow to ischaemic brain. A phase 2 study comparing mild hypercapnia with normocapnia in 50 postcardiac arrest patients documented a lesser increase in neuron-specific enolase (NSE) values in the hypercapnia group (Eastwood et al. 2016). A RCT comparing post-cardiac arrest patients ventilated to either normocapnia or mild hypercapnia (6.6–7.3 kPa) starts recruiting soon (Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) [clinicaltrials.gov/ct2/show/NCT03114033]). Mild hypothermia has been shown to improve neurological outcome from OHCA presenting with a shockable rhythm, but the two prospective studies documenting this are now considered to be of moderate to low quality (Bernard et al. 2002; Hypothermia After Cardiac Arrest Study Group 2002). The targeted temperature management (TTM) study showed no difference in neurological outcome between all-rhythm OHCA patients with ROSC who had their temperature controlled for 24 h at 33oC versus 36oC (Nielsen et al. 2013). Temperature control for comatose survivors of OHCA is still important, but within the range of 32–34oC there is no consensus on the optimal target temperature (Donnino et al. 2016). The Hypothermia or Normothermia-Targeted Temperature Management After Out-of-hospital Cardiac Arrest-trial (TTM-2 [clinicaltrials.gov/ct2/show/NCT02908308]) study will start recruiting soon and will randomise comatose OHCA survivors to temperature control at 33oC versus prevention of fever, with temperature control to a target of 37.5oC initiated only if the patient’s temperature reaches 37.8oC. The commonest mode of death in postcardiac arrest patients who are admitted to ICU but do not survive is withdrawal of life-sustaining therapy (WLST) following determination of a poor neurological prognosis. We now recognise that in many cases these WLST decisions have been premature and that prognostic tests previously thought to be reliable are associated with unacceptably high false positive rates (Elmer et al. 2014; Cronberg et al. 2017). European guidelines for prognostication in comatose post-cardiac arrest patients advocate a multimodal approach that is delayed until at least 3 days after cardiac arrest (Sandroni et al. 2014). Those ICUs experienced in the management of post-cardiac arrest patients should have easy access to electroencephalography, including somatosensory evoked potentials, and to neurologists who can interpret the findings. In some countries, regionalisation of postcardiac arrest treatment has resulted in cardiac arrest centres with availability of 24/7 coronary catheterisation laboratories, intensive care teams experienced in post-resuscitation care and neurologists that can help in the interpretation of neuroprognostic tests (Spaite et al. 2014). The introduction of cardiac arrest centres where high volumes of post-cardiac arrest patients can be treated is associated with better outcomes, even when patients are transported for greater distances as they bypass local hospitals (Tranberg et al. 2017; Schober et al. 2016; Elmer et al. 2016). Investigators in London, UK are about to start recruiting to a study patients with ROSC after OHCA of likely cardiac cause but without STE on their 12-lead ECG, and will compare the outcome of patients randomised to be transported to the nearest acute hospital with those taken to a regional cardiac arrest centre (Patterson et al. 2017). This study will help to determine if all OHCAs of cardiac cause should be treated in a cardiac arrest centres and not just those patients with STE on their 12-lead ECG. By strengthening every link in the chain of survival it is likely that survival from cardiac arrest can still be improved considerably. Conflict of Interest Jerry Nolan is Editor-in-Chief of Resuscitation. He has a UK National Institute of Health Research (NIHR) grant for the PARAMEDIC-2 study (adrenaline versus placebo in out of hospital cardiac arrest-OHCA) and for the AIRWAYS-2 study (i-gel versus tracheal intubation in OHCA). AED automated external defibrillator ICU intensive care unit MAP mean arterial pressure NSE neuron-specific enolase OHCA out-of-hospital cardiac arrest PAD public access defibrillation PCI percutaneous coronary intervention pVT pulseless ventricular tachycardia ROSC return of spontaneous circulation RCT randomised controlled trial TTM targeted temperature management VF ventricular fibrillation WLST withdrawal of life-sustaining therapy

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New computational studies could help scientists unpick the knots in real proteins A new study may help scientists unravel the complex problem of protein folding. The study suggests knotted proteins, which present a particular challenge to folding experts, could be untied with a couple of well-targeted tugs. Protein function is intimately related to protein folding. The folding process, however, remains something of a mystery and due to its speed is almost impossible to observe. Knotted proteins, discovered relatively recently, are puzzling because it is unclear how they could fold through any of the routes so far identified. Experimentally, it’s also difficult to tell whether a protein that has been denatured is still knotted - or not. Joanna Sulkowska at the University of California-San Diego in the US and colleagues have now employed computational methods to show that knots in methylotransferase proteins could be unpicked by pulling on exactly the right residues. Using simple equations, they pinpoint the knot and its key residues relative to the protein’s ends. Their molecular dynamics simulations support the idea that pulling in the right places will undo the knot. ’Up to now there was no way to unfold the protein and this paper suggests that, yes, you can untie it, but you need to pull in very particular spots,’ says Sulkowska. ’Then you can study the full folding mechanism.’ The right spots, Sulkowska explains, could act as attachment sites for cantilever tips, which could then be used to untie a knot under an atomic force microscope. She says the method should apply to all knotted proteins so far discovered. ’The work will be important for the interpretation of mechanical unfolding studies,’ says Sophie Jackson, a protein folding expert at the University of Cambridge, UK. But she adds that mechanical unfolding is a ’special case’ - unfolding in thermal and chemical denaturation experiments proceeds by a different route. Sheena Radford, who studies folding mechanisms at the University of Leeds, UK, thinks the work is intriguing, but leaves plenty to the imagination. ’Although it allows us to see whether you could unknot a protein when you pull it in different directions, I don’t think it answers the question that for me is most fascinating, which is how biology ever knotted it in the first place.’ It’s like asking a three-year-old to untie a shoelace, she says - that may be easy, but re-knotting it will be much harder. et alJ. Am. Chem. Soc.DOI: /ja102441z

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Three Americans win Nobel medicine prize for body rhythm work [But they failed to link Americanism to Creationism] She returned to China after training in the United States of America, but is a good example of someone who appears to practice Americanism, which is an ideology that appears to be integrated into her research. I do not know what people in China refer to in the context of this ideology. In the words of Theodore Roosevelt, “Americanism is a question of spirit, conviction, and purpose, not of creed or birthplace.” After Ben Feringa (Chemistry/chirality) and Yoshinora Ohsumi (Physiology or Medicine/autophagy) won last year, I thought that all gene-centric nonsense would be eliminated. It became perfectly clear that energy-dependent changes in chirality must be linked to autophagy, which protects all organized genomes from the virus-driven degradation of messenger RNA. Excerpt 1) The awardees’ work stems back to 1984, when Rosbash and Hall, who was then also at Brandeis, along with Young isolated the “period gene” in fruit flies. Hall and Rosbash found that a protein encoded by the gene accumulated during the night and degraded during daytime. A decade later, Young discovered another “clock gene.” Excerpt 2) “The paradigm-shifting discoveries by the laureates established key mechanisms for the biological clock,” the Nobel Assembly said in its prize statement. for their discoveries concerning organization and elicitation of individual and social behaviour patterns. The organization and elicitation of individual social patterns of behavior is energy-dependent and it links what organisms eat to the metabolism that links the energy to the physiology of pheromone-controlled reproduction in species from microbes to humans. Since 1973, and especially during the past 13 years, there has not been a gene-centric theory that has successful been linked to a paradigm shift. For example, all paradigm-shifting Nobel Prizes in Physiology or Medicine during the past 13 years have linked the energy-dependent creation of ATP and the creation of messenger RNA to protection from the virus-driven energy theft that serious scientists have linked from the degradation of messenger RNA to all pathology. See for examples: 2016: Yoshinori Ohsumi of Japan for his work on autophagy—a process whereby cells “eat themselves”—which when disrupted can cause Parkinson’s and diabetes. 2015: William Campbell (US citizen born in Ireland) and Satoshi Omura (Japan), Tu Youyou (China) for unlocking treatments for malaria and roundworm. 2014: John O’Keefe (Britain, US), Edvard I. Moser and May-Britt Moser (Norway) for discovering how the brain navigates with an “inner GPS”. 2013: Thomas C. Suedhof (US citizen born in Germany), James E. Rothman and Randy W. Schekman (US) for work on how the cell organises its transport system. 2012: Shinya Yamanaka (Japan) and John B. Gurdon (Britain) for discoveries showing how adult cells can be transformed back into stem cells. 2011: Bruce Beutler (US), Jules Hoffmann (French citizen born in Luxembourg) and Ralph Steinman (Canada) for work on the body’s immune system. 2010: Robert G. Edwards (Britain) for the development of in-vitro fertilisation. 2009: Elizabeth Blackburn (Australia-US), Carol Greider and Jack Szostak (US) for discovering how chromosomes are protected by telomeres, a key factor in the ageing process. 2008: Harald zur Hausen (Germany), Francoise Barre-Sinoussi and Luc Montagnier (France) for work on the viruses causing cervical cancer and AIDS. 2007 Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells. 2006 Andrew Z. Fire and Craig C. Mello for their discovery of RNA interference – gene silencing by double-stranded RNA. 2005 Barry J. Marshall and J. Robin Warren for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease. 2004 Richard Axel (US) and Linda Buck (US) for their discoveries of “odorant receptors and the organization of the olfactory system. Endogenous RNA interference is the energy-dependent epigenetic link from the physiology of pheromone-controlled reproduction to biophysically constrained viral latency. The stress-linked virus-driven degradation of messenger RNA has been linked to all pathology. This morning I spoke with a 10-year veteran who had served in Iraq. He was not happy with the treatment for PTSD that he was receiving from the VA because he and his wife know he is getting worse (e.g., hyper-vigilance and more nightmares). If you let our veterans, as individuals, continue to think they are less than human because a mutation or something else causes their failure to adapt to the challenges of life after returning from military service overseas, how will you convince yourself that you are not contributing to the death rate by suicide? Other lawmakers woke up to the news and offered thoughts and prayers. Governor Brian Sandoval of Nevada called the shooting a “heinous act of violence.” All heinous acts of violence are caused by the virus-driven degradation of messenger RNA, not by the natural selection for mutations as claimed in Mutation-Driven Evolution (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation. See for comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model …the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

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- a black nymphalid butterfly, Melitaea phaeton, characterized by orange-red, yellow, and white markings, common in those areas of the northeastern U.S. where turtlehead, the food plant of its larvae, is found. - David,born 1938, U.S. microbiologist: Nobel Prize in Medicine 1975. - Lord. Sir George Calvert. - a seaport in N Maryland, on an estuary near the Chesapeake Bay. - a port in N Maryland, on Chesapeake Bay. Pop: Pop: 628 670 (2003 est) - David . born 1938, US molecular biologist: shared the Nobel prize for physiology or medicine (1975) for his discovery of reverse transcriptase - Lord .See Calvert (def. 1) city in Maryland, U.S., founded 1729, named for Cecilius Calvert (1605-1675), 2nd baron Baltimore, who held the charter for Maryland colony; from a small port town in southern Ireland where the family had its seat, from Irish Baile na Tighe Mor, literally “townland of the big house.” In old baseball slang, a Baltimore chop was a hit right in front of the plate that bounced high. - American microbiologist. He shared a 1975 Nobel Prize for research on the interaction of tumor viruses and genetic material. - American microbiologist who discovered the enzyme reverse transcriptase, which is capable of passing information from RNA to DNA. Prior to this discovery, it was assumed that information could flow only from DNA to RNA. He won a 1975 Nobel Prize for his research into the connection between viruses and cancer. Largest city in Maryland.

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The Future Now: Science and Technology What are the big ideas and new technologies emerging today with the potential to make a major impact on all our futures? This strand aims to provide short, accessible explanations of the latest developments in science and technology followed by expert discussion of the possibilities and problems that arise. For example, while Blockchain - an internet-based, seemingly tamper-proof ledger - may not seem terribly exciting, it is the basis of the virtual currency Bitcoin and holds the potential to transform many legal and financial activities worldwide. Genome editing has the potential to cure a wide variety of congenital conditions - but what of the potential for genetic engineering for malicious purposes as well as beneficial ones? Should we even be tampering with our genes in this way at all? From the pros and cons of Big Data to whether nuclear power is the future, this strand should be an eye-opener for anyone interested in science and technology.

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As the CAO, he uses his expertise in microbiome science and machine learning methodologies to guide the company’s strategy for translating copious amounts of cell-free microbiome data into patient diagnoses. At only age 28, Micronoma is Greg’s third corporation and was strongly inspired by the unexpected stage IV diagnosis and tragic sudden loss of his grandmother to pancreatic cancer while attending college. Sarah Schenck is a writer, director, and producer. She uses storytelling to advance public health goals for diverse audiences. Sarah creates shorts for nonprofits and teaches meditation at St. Francis Friends of the Poor. While serving as the NYC Comptroller’s Senior Education Policy Advisor she taught herself filmmaking. Sarah directed, produced, and was the correspondent for Saving Carla, a film on childhood obesity that aired on PBS. She co-founded ParentEarth, dedicated to healthy food for all families. Her films have won awards at festivals worldwide. Sarah’s latest film, The Invisible Extinction, showcases the critical role microbes play in human health. Head of Microfluidics Hervé is the Head of Microfluidics of Xsensio. He leads the development of innovative solutions for the collection and transport of novel biofluids for the Lab-on-SkinTM sensing platform. After a MSc in Physics at ENS Ulm, he earned a PhD in fluid-structure interactions from Sorbonne Université. Before joining Xsensio, Hervé obtained several grants to join international research groups in Santiago de Chile and EPFL, where he unraveled new fundamental knowledge in 2D materials and microfluidics. Xsensio SA is a swiss start-up that develops innovative wearable systems that continuously monitor our physiological state to detect risks in real-time. Chief Scientific Officer Eddie Adams is the Chief Scientific Officer of Micronoma, Inc. At Micronoma he leads the development of the Oncobiota™ cell-free microbial DNA liquid biopsy assays for cancer detection. He received his PhD in Biological Chemistry in Peter Seeberger’s laboratory from the Massachusetts Institute of Technology and carried out postdoctoral work in innate immunity with Prof. Nir Hacohen at Harvard Medical School. His industrial research career has encompassed development and successful commercialization of products in nanotechnology, epigenetics, microbiome sample preparation solutions, and disease diagnostics for sepsis and cancer. Eddie is an inventor on 17 issued patents and numerous patent applications. Assay Development Lead & Co-Founder Hanie is a biotech innovator and the co-founder of Arma Biosciences with experience in development of biomedical devices. Focused on combination of surface chemistry, electrochemistry and molecular biology during the past seven years, Hanie has developed multiple patented sensing technologies for food safety, and disease monitoring. Director of RnD & Co-Founder Surath is an engineer and academic who co-founded Arma Biosciences, developing a platform biosensing technology rooted from his PhD work published in Nature Chemistry. His passion for science is seen in his publications, patents, and in having organised Canada’s foremost science outreach festival, Science Rendezvous. He is the CEO and Co-founder of AIcrowd, a platform for organising machine learning challenges on a variety of problems in OpenScience using OpenData. The vision is to enable Scientists from multiple domains to crowdsource machine learning expertise; and in the process also facilitate the grooming of machine learning expertise in a coopetitive environment. He was previously working as a PhD student at École polytechnique fédérale de Lausanne (EPFL), Switzerland working on a diversity of problems in Applied Machine Learning from detection of Plant Diseases from images of Plant leaves to teaching musculoskeletal models how to walk using reinforcement learning. Currently Mohanty is involved in the MyFoodRepo project. University of Strathclyde Damion Corrigan is a Lecturer and Chancellor's Fellow in the Department of Biomedical Engineering at the University of Strathclyde. His area of expertise is the electrochemical detection of disease markers, particularly for infectious conditions. Based on core expertise in electrochemical sensing, analytical chemistry and device fabrication his research aims to develop improved diagnostic tests for clinically important conditions such as, drug resistant bacterial infections, COVID-19, sepsis, cancer and epilepsy. Adrian is a co-founder of Xsensio, and its CSO. He is also a full Professor at EPFL, where he leads the Nanolab. He received his Ph.D. degree from the National Polytechnic Institute of Grenoble in France, and has held staff and/or visiting positions at LETI-CEA and LPCS-ENSER in Grenoble, at Stanford University, and at Tokyo Tech. He has published more than 350 articles in international journals and conference. Director of Biosensing Ron is the CTO of Xsensio, where he leads the development of the company’s proprietary Lab-on-Skin™ sensing platform. He holds a PhD in Chemistry, B.Sc in Materials Engineering and a B.A. in Physics. Before joining Xsensio, he spent several years developing novel biosensing concepts as an assistant professor at the University of Twente in the Netherlands and then moved to industry and worked as the CTO of the Dutch start up Biovolt BV, where he was managing the technology development of diagnostics assays for metabolic syndrome related health issues. Xsensio SA is a swiss start-up that develops innovative wearable systems that continuously monitor our physiological state to detect risks in real-time. Esmeralda is the CEO of Xsensio, a company she co-founded a few years ago. Prior to Xsensio, she had several years of experience as manager at Boston-based investment firm Commons Capital where she was in charge of screening investment opportunities in a partnership with the Bill and Melinda Gates Foundation. She earned her MBA at the Massachusetts Institute of Technology (MIT), a B.S. and M.S. in Economics from ULB, Belgium and an executive degree in management from EPFL. Adrian Heuss is a strategy consultant, conceptionalist and editor at advocacy. Initially, he wrote as a science journalist for various Swiss daily newspapers. After graduating from the Ringier School of Journalism, he worked for an international communications agency. He supported the feasability study of the microbiota vault. As an Associate Professor of Epidemiology and Director of MD Anderson Cancer Center’s Bionutrition Research Core, my long-term goal is to refine and inform evidence-based dietary recommendations across the cancer continuum. Building on my training at Emory University, the American Cancer Society and the National Cancer Institute, my research at MD Anderson is increasingly motivated by the many unanswered questions and complexities surrounding nutrition, obesity, and the microbiome in our patients. Together with clinical and laboratory colleagues, we carefully collect data and “observe” habits, while pushing forward to more definitively answer these questions in dietary intervention trials. Rob Knight is the founding Director of the Center for Microbiome Innovation and Professor of Pediatrics, Bioengineering, and Computer Science & Engineering at UC San Diego. He is a Fellow of the American Association for the Advancement of Science and received the 2017 Massry Prize. His lab has produced many of the software tools and laboratory techniques that enabled high-throughput microbiome science, including QIIME and UniFrac. His work has linked microbes to a range of health conditions, enhanced our understanding of microbes in many environments, and made high-throughput sequencing accessible to thousands of researchers around the world. Kings College London Dr. Nathan is consultant medical oncologist at Mount Vernon Cancer Centre, Northwood, UK. His specialist interests are the treatment of malignant melanoma and renal cell carcinoma. His clinical training was through Cambridge and London having had an earlier scientific career in academia and the pharmaceutical industry. He leads many academic and pharma sponsored clinical trials and has authored many high impact paper. He is a trustee of Melanoma Focus the UK national melanoma charity. He is EORTC Uveal Melanoma lead, International Rare Cancer Initiative (IRCI) UK Uveal melanoma lead and chairs the UK guideline group on Uveal Melanoma. I am a medical oncologist at the department of Medical Oncology of the UMCG, the Netherlands. I studied biochemistry and medicine. I obtained my PhD degree in 1989 with the thesis ‘Mechanisms and circumvention of cellular resistance to cisplatin”. During my Dutch Cancer Society (KWF) fellowship I worked on gene therapy topics in several labs in the Netherlands, the UK (Chester Beatty Laboratories, London) and Belgium (Ludwig Institute, Brussels) and I was trained as a medical oncologist. At 1995 I started as a trained medical oncologist at the University Medical Center Groningen, the Netherlands. In 2011 I was appointed as a professor at the Department of Medical Oncology. My recent clinical research topics are to improve clinical outcome of patients with (locally) advanced melanoma, patients with locally advanced rectal cancer and to develop innovative molecular imaging techniques using whole body PET/CT on for example targets as PD-L1 and hormone receptors. Yan (Janie) Jiang Janie is a program/laboratory manager at MD Anderson Cancer Center. She received a PH.D. in nutritional biochemistry from Purdue University in West Lafayette Indiana. She did a postdoctoral training at University of Michigan in Ann Arbor Michigan. The research she is working on is around Dr. Jennifer McQuade’s “a control feeding study to investigate impact of dietary fiber on gut microbiome and immunity in melanoma patients”. - Diet and Nutrition Michal Rein is a registered dietitian, specializing in dietary interventions and modifications. Michal has a master in M.sc from the Ben-gurion university of the Negev and is currently a PhD student under the joint supervision of Prof Eran Segal from Weizmann institute ang Prof Shira Zelber-Sagi from the university of Haifa. As a researcher Michal is studying the effect of algorithm based personalized dietary recommendations tailored by the prediction of glycemic responses on the improvement of metabolic parameters and glycemic balance in various populations including healthy individuals, subjects with glucose intolerance and breast cancer survivors. Additionally, Michal is part of an ongoing developmental team studying the association between personal characteristics, food consumption and the emerging area of deep phenotyping and multi-omic data. Specifically on the influences of individual reaction to glucose and other health indicators. Personally, she chose to focus on nutrition thanks to the role it plays in health promotion and disease prevention and trying to invent tasty and easy recipes for her patients and family. - Personalized dietary modification based on postprandial targeting diet - Randomized clinical trial - design and monitoring - Diabetes management Thomas Vogl obtained a PhD in Molecular Biomedical Sciences in Austria. He was a visiting scientist at the Queensland University of Technology in Brisbane focusing on genomics. After working in the R&D department of Sandoz (Novartis) on biopharmaceutical production, he moved as a senior postdoc to the Weizmann Institute of Science (group of Prof. Eran Segal). Working on the interface between basic and applied research, Thomas is aiming to unravel interactions of the immune system with the microbiome. As a Seerave Fellow, Thomas is involved in profiling immune responses of cancer patients as well as developing novel COVID-19 diagnostics. Leveraging high throughput antibody repertoire profiling methodologies, they have created a novel high precision diagnostic for the detection of coronavirus (CoV) antibodies. This approach has for the first time revealed extensive cross-reactivity with animal CoVs, suggesting a novel diagnostic strategy for detecting future spillovers to humans. - Microbiota-immune axis - Machine learning Roni has a practical electronics engineering from the national Handesaim school at the Technion, her final project was creating small gaming console from a processer screen and a mouse. Her bachelor is at biomedical engineering from the Technion, her final project was Vocal Vibes, were we used mechanical sensors as well as microphone and image analysis to assess vocal performances in basic speech therapy exercises, the project won first place at the entrepreneurs’ competition. Her current research is in Naama Geva-Zatorsky lab, studying the effect different nutrition and carbohydrate sources has on the microbiome functionality and how that mediate the changes nutrition has on the immune system. Eran Segal is a Professor at the Department of Computer Science and Applied Mathematics at the Weizmann Institute of Science, heading a lab with a multi-disciplinary team of computational biologists and experimental scientists in the area of Computational and Systems biology. His group has extensive experience in machine learning, computational biology, and analysis of heterogeneous high-throughput genomic data. His research focuses on Microbiome, Nutrition, Genetics, and their effect on health and disease. His aim is to develop personalized medicine based on big data from human cohorts. Naama is combining systems-biology with microbiology and immunology to study the interactions between gut microbes and the host immune system in health and disease. She has characterized the host response to a variety of gut microbes and has applied a metabolic labeling approach to fluorescently label the anaerobic gut microbes. In addition, she is studying microbial genetic mechanisms that allow gut microbes to thrive the dynamic gut ecosystem and to co-op with bacteriophage. She is a recipient of the Alon Fellowship, the national and international UNESCO-L’Oreal award, the Human Frontiers fellowship, the EMBO fellowship, the John F. Kennedy Prize, the Teva Prize, and the Barenholz prize, for academic excellence. Naama received her B.Sc. from Tel Aviv University, double-majoring in Chemistry and Biology, with summa cum laude honors. Her M.Sc. and Ph.D., are from the Weizmann Institute, studying systems-biology of protein dynamics in cancer, with Prof. Uri Alon, completed with honors. Her postdoctoral training was at Harvard Medical School, studying gut microbiota-host interactions with Prof. Dennis Kasper. Tal Gefen (PhD) is a lab manager and research associate at Naama Geva-Zatorsky’s lab “Microbiome – Host interaction”, Technion, Israel. Tal has graduated the Hebrew university of Jerusalem, where he conducted a research focusing on immunogenicity of therapeutic proteins. Later, as a postdoc under the guidance of Professor Eli Gilboa at University of Miami, he specialized in cancer immunotherapy and developed a novel molecule for the inhibition of checkpoint blockage via the TIM-3 receptor, expressed on exhausted T cells. At the Geva-Zatorsky’s lab, he is mainly focusing on microbial-immunological technology integration, development, and projects management. Following a bachelors in Biochemistry and masters in Computational Biology, Thomas completed a PhD in Computational and Systems Biology at MIT. As a postdoc, also at MIT, he began studying the clinical impact of the gut microbiome with Prof. Eric Alm at the MIT Center for Microbiome Informatics and Therapeutics. It was during this time that he developed an interest in how we can use dietary interventions to shape the composition and metabolic output of the microbiome for therapeutic purposes. This led him to work on building a framework around personalised dietary fibre supplementation aiming to boost Short Chain Fatty Acid (SCFA) production in the gut. Thanks to the support of Seerave, Thomas has launched a clinical trial investigating the impact of different diets on plasma SCFAs and circulating markers of inflammation. - Diet and the gut microbiome - Short Chain Fatty Acids - Machine learning Noa is a PhD student in Namma Geva-Zatorsky’s lab, at the faculty of medicine, Technion, Israel. She received her BSc in Biochemical Engineering from the Chemical Engineering faculty at the Technion. She then started her Master’s degree in the Geva-Zatorsky lab and transitioned to the direct PhD tract. Her research project aims to reveal the environmental effects on the immunomodulatory functionality of gut bacteria . Her study combines microbiology and immunology using in vitro high throughput methods and Germ Free mice models. In the Seerave project she studies the mechanistic link between diet, gut bacterial immunomodulatory functionality and cancer. She does so by defining the effects of different carbon sources on bacterial immunomodulatory functionality in vitro, as well as the effects of diets on gut bacteria immunomodulatory functionality in gnotobiotic mice cancer models. - Gut immunology - GF mice models - Bacterial metabolites Marcel Salathé is a digital epidemiologist working at the interface of health and computer science. An associate Professor at EPFL where he heads the Digital Epidemiology Lab, Marcel works at the forefront of artificial intelligence and its application in health and other domains. His lab spun off AIcrowd, an AI challenge platform whose goal is to accelerate research on AI across multiple domains, and which is used by organizations such as OpenAI, Microsoft, Google, Amazon, Stanford University, and many others. Marcel is the founder of the MyFoodRepo platform, an AI-assisted tool to revolutionize food tracking in research cohorts. Tessa is the Sr. Clincal Studies Coordinator in the Department of Melanoma and the McQuade Lab at MD Anderson Cancer Center. She received a MPH in Public Health, Epidemiology from the University of North Texas Health Science Center. She is currently working on Dr. Jennifer McQuade’s phase II clincal trial, “Diet and Immune Effects Trial: DIET – A randomized double blinded dietary intervention study in patients with metastatic melanom receiving immunotherapy“. Her main role is the recruitment and enrollment of patients to the phase II clinical trial and is the primary patient contact from the time of enrollment throughout their participation in the study. - The DIET Study - Melanoma Clinical Trials - Melanoma diet studies Talia Elena Salzmann Dr. Jennifer Wargo is a professor, Department of Genomic Medicine, Division of Cancer Medicine, and professor, Department of Surgical Oncology, Division of Surgery, at The University of Texas MD Anderson Cancer Center. With a joint appointment in Surgical Oncology and Genomic Medicine, Professor Wargo leads critical research to better understand responses to therapy and to develop novel strategies to combat resistance. This includes her groundbreaking recent work elucidating the role of the gut microbiome in shaping responses to immunotherapy in patients with melanoma—with a manuscript describing this work published in Science and a clinical trial underway exploring optimal methods to manipulate the gut microbiome to enhance responses to cancer therapy. She is recognized internationally as a leader in cancer research and is leading innovative efforts globally. Dr. McDonald is the Scientific Director for The Microsetta Initiative and the American Gut Project, run by the School of Medicine at UC San Diego. His research focuses on the complex microbial communities associated with humans, with the environment, and how to scale microbiome analysis to large sample sizes. He has played central roles in the development of highly cited analysis tools, such as QIIME, Qiita, and PICRUSt, a Genomic Standards Consortium file format called BIOM, and Greengenes, one of the main microbial taxonomies used in the field. Dr. McDonald received a BS and PhD in Computer Science from the University of Colorado at Boulder. Jennifer Leigh McQuade Dr. McQuade is a melanoma medical oncologist and physician-scientist at MD Anderson hosting a translational research program focused on understanding the interaction between host-level factors, tumor biology, immunity and outcomes. She is published in 41 peer-reviewed original research articles and authored or co-authored on 3 dozen other articles, abstracts and editorials. She has presented at conferences across the nation and has been featured in articles from both The New York Times and The Houston Chronicle for her paper in The Lancet Oncology titled Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Ashley E. Holly Dr. Holly received her PhD from Cleveland State University with her doctoral research completed at the Cleveland Clinic. Her robust training in protein biology coupled with a strong interest in nutritional biochemistry led her to serve as a Research Scientist in the McQuade Lab at MD Anderson, where she was part of a team that performs controlled feeding studies. Her thirst for knowledge led Dr. Holly to earn an MBA degree giving her a unique skill set in the field! Currently, Dr. Holly is a Fellow in the Sharifi Lab at the Cleveland Clinic investigating diet, metabolism, and Prostate Cancer. Sandrine Miller-Montgomery, Pharm.D., Ph.D. is the Co-Founder, President and CEO of Micronoma, the first cancer-detection company using liquid biopsy technology to detect and predict cancer at an early stage of the disease by analyzing the microbial signal with clinical-grade accuracy. Prior to this, she was executive director of UC San Diego’s Center for Microbiome Innovation that she co-led with Dr. Rob Knight. Before her time in academia, she had worked in large biotech and multinational companies as well as start-ups where she excelled at preparing companies for successful exits as shown by her work at Helixis, acquired by Illumina, and MO BIO Labs acquired by QIAGEN. Unisversity of Trento Andrew obtained his bachelor’s in Biology from Mackenzie University and was an intern at the Institute of Psychiatry investigating genetic polymorphisms associated with Alzheimer’s and Parkinson’s disease. For his Master’s in Oncology dissertation, obtained from AC Camargo Cancer Centre, he investigated the effects of alcohol and tobacco consumption on the oral microbiota. He obtained his PhD in Bioinformatics from the University of Sao Paulo. During his academic training, he has worked on several projects that included: "Studies of microbial diversity in the Zoological Park of the State of São Paulo (University of Sao Paulo)”, "Effects of short-chain fatty acids produced by probiotic bacteria in the prophylaxis and treatment of allergic airway inflammation” (Federal University of Sao Paulo) and “Identifying reproducible gut microbial signatures to detect colorectal cancer” (University of Trento). Currently, he is part of the Horizon 2020 funded project ”Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response”, where he supports project partners with computational analyses of gut microbiomes from several different cancer types. His current role in Seerave is to help in the analysis of the gut microbiome and response to immunotherapy in the PRIMM cohorts (King’s College London, University of Groningen and University of Trento). Kevin the co-founder of Biomsense and is a skilled STEM commercialization leader with more than eight years’ experience in the healthcare space. Prior to joining BiomeSense, Kevin provided strategic and operational leadership as the Director of Operations for a seed-stage pharmacogenomics spinoff from the University of Chicago. University of Trento Nicola Segata, Ph.D., is Professor and Principal Investigator in the CIBIO Department at the University of Trento (Italy) and Principal Investigator at the European Institute of Oncology in Milan (Italy). His lab (http://segatalab.cibio.unitn.it/) employs experimental metagenomic tools and novel computational approaches to study the diversity of the microbiome across conditions and populations and its role in human diseases. The projects in the lab bring together computer scientists, microbiologists, statisticians, and clinicians and are generally focused on profiling microbiomes with strain-level resolution and on the meta-analysis of very large sets of metagenomes with novel computational tools. Dr Bataille has been practising dermatology since 1989 in many teaching hospitals in London. She completed her PhD in 1995 at the CRUK/Royal London Hospital, London. In 2004, Dr Bataille moved to the West Hertfordshire NHS Trust where she runs a melanoma genetic clinics and supports the oncologists at the Mount Vernon Cancer Centre. Dr Bataille has been involved in many research projects over the last 25 years looking at the genetics of melanoma, naevi, pigmentation, gut microbiome and COVID skin manifestations. She has published extensively over the last 30 years Her H index on Google Scholar is 54. Maria Gloria Dominguez Maria Gloria Dominguez-Bello is the Henry Rutgers Professor of Microbiome and Health at Rutgers University. Her lab studies the impacts of modern practices on microbiomes, and strategies for restoration. She is a Fellow of the Infectious Disease Society of America (IDSA), and of the American Academy of Microbiology, and is a cofounder of the Microbiota Vault, a global initiative to preserve the diversity of the microbes relevant to human health. Tim Spector is a medically qualified Professor of Epidemiology and Director of the TwinsUK registry at King’s College London. His current work focuses on the microbiome and nutrition, and he is co-founder of the data science company ZOE Ltd which has commercialised a home kit for personalised nutrition . He also the lead researcher behind the world's biggest citizen science health project - the ZOE Covid study of over 4 million people for which he was awarded an OBE. Having published more than 900 research articles, he is ranked in the top 100 of the world’s most cited scientists by Google. He is the author of four popular science books, including "The Diet Myth” and the most recent "Spoon Fed" which is a Sunday Times bestseller. He makes regular appearances on social and mainstream media. Martin Blaser serves as Henry Rutgers Chair of the Human Microbiome and Director, Center for Advanced Biotechnology and Medicine at Rutgers University. For 20 years, he has been investigating the relationship of the human microbiome with the epidemics of obesity, diabetes, and asthma. He was President, Infectious Diseases Society of America, elected to the National Academy of Medicine and American Academy for Arts and Sciences, and currently chairs the Presidential Advisory Council for Combatting Antibiotic-Resistant Bacteria (PACCARB). He wrote Missing Microbes, now translated into 20 languages. Karla Lee received her medical degree from Trinity College Dublin in 2012 and commenced early medical training in Dublin. In 2016 she completed an MSc at the Royal College of Surgeons, Ireland and moved to London to pursue academic oncology training. She is training as a medical oncologist at The Royal Marsden Hospital in London and has taken time away from this training to pursue a PhD at King’s College London. She is in the final year of her PhD and is working on a thesis investigating the impact of the gut microbiome and a number of other „omics“ on immune checkpoint inhibition for advanced melanoma. Karla hopes to combine academic and clinical work in her future career. Dominik Steiger is Chief Executive Officer at EvalueScience Ltd, a consulting company specialized in advice, research, and conceptualization in the fields of biomedicine, health, and digital health. His work focusses on idea development and project management at the interfaces of research, policy, and regulation. He is coauthor of the Microbiota Vault Feasibility Study. As Secretary of the Microbiota Vault, he coordinates the launch of the initiative. Professor Jack A Gilbert is a Professor in Pediatrics, the Scripps Institution of Oceanography, and Director of the Microbiome Core at University of California San Diego. He uses molecular analysis to test fundamental hypotheses in microbial ecology. Dr. Gilbert cofounded the Earth Microbiome Project, the Microbiota Vault, helps coordinate the American Gut Project, and cofounded BiomeSense Inc to develop microbiome collection tools. He has authored more than 350 peer reviewed publications and book chapters on microbial ecology and is the founding Editor in Chief of mSystems journal. University of Basel Prof. Adrian Egli is the Head of Clinical Bacteriology and Mycology of the University Hospital Basel and a research group leader at the Department of Biomedicine at the University of Basel. His research focuses on host-pathogen interaction and he and his team aims to understand antibiotic resistance and virulence development in single bacterial species and bacterial communities. He has published more than 150 articles, including high-ranked journals such as Nature Medicine, Nature, Plos Pathogens, and many more. Prof. Egli coordinates large national incentives in Switzerland including the SPHN/PHRT funded Personalized Swiss Sepsis Study and the Swiss Pathogen Surveillance Platform. He is a member of the Microbiota Vault pilot team in Switzerland. Johannes Björk is a computational ecologist specialising in microbiome analysis through the lens of ecological theory. He received his PhD from the Polytechnic University of Barcelona under the supervision of theoretical ecologist José M. Montoya. In his dissertation, Johannes studied the structure and dynamics of the complex sponge-microbe interaction networks. Thereafter, he did a postdoc working on the gut microbiome of wild baboons. In this project, Johannes applied time-series models to better understand the relative contribution of the external environment, social interactions and host demographics in shaping the gut microbiome over time. Johannes is currently a Seerave postdoc working in the group of Rinse Weersma at the University Medical Center Groningen where he applies his unique perspective to increase our understanding of the gut microbiome’s role in ICI treatment to advanced melanoma. - Microbiome ecology - Longitudinal analysis - Multi-omic analysis - System biology University of Lausanne Pascale Vonaesch, MSc, MPH, PhD is an Assistant Professor at the University of Lausanne and a Principal Investigator within the NCCR Microbiomes. She was trained as a Microbiologist at the ETH in Zürich and the Ecole Normale Supérieure in Paris and subsequently performed her PhD thesis at the Institut of Microbiology at the ETH in Zürich, Switzerland on host-pathogen interactions and a postdoctoral research stay at the Institut Pasteur, Paris, France, where she initiated and led the Afribiota project, a translational research project aimed at eludicating the pathophysiology underlying stunted child growth. She then joined the Swiss Tropical and Public Health Institute for two years as a senior postdoc/ junior group leader to continue her work on undernutrition before moving with her group to the University of Lausanne. Her lab focuses on fundamental and translational/clinical research on the human intestinal ecosystem and the contribution of the microbiota to health and disease. In her research, she is especially interested in the role of the intestinal microbiome in childhood malnutrition and in the development of microbiota-targeted interventions. Laura Bolte is a dietician currently pursuing an MD and PhD at the University Medical Center Groningen (UMCG). In 2013 she graduated in Nutritional sciences in Germany, where she performed research on diet-mediated endocrine and metabolic changes in diabetes, obesity and malnutrition. In 2017 she started her medical training which she is currently completing at the European Medical School Oldenburg-Groningen. Since 2019 she pursues a PhD in the group of Prof. Rinse Weersma to further investigate the therapeutic potential of diet and its role for the human gut microbiota. Her current research as a Seerave fellow aims to identify dietary factors and microbial targets to improve responsiveness to immunotherapy in cancer patients. - diet-microbiome interaction - intestinal inflammation Christoph von Bieberstein Christoph is co-founder and commercial director of HexagonFab. Before, Christoph was a senior consultant for McKinsey & Company working with a particular focus in market access for new therapeutics and vaccines in developed and emerging markets. Christoph holds a Master’s degree in Strategy and International Management from the University of St.Gallen. During his studies Christoph co-founded the non-profit organisation Liter of Light in Switzerland, the grass-roots solar-bottle movement to bring light to underprivileged communities around the world. Seerave has placed a seed investment into Hexagon Fab. Further, Hxagon Fab is a consortium member of the DIP project. Ruizhi Wang is the Founder of HexagonFab is a start-up company based in Cambridge UK, The mission of HexagonFab is to create instruments that enable scientists to understand how proteins behave and what their properties are, faster, more accurately and more easily than ever before. During his PhD in Engineering at the University of Cambridge, Ruizhi worked on the scalable production of nanomaterials and processes to integrate these into devices such as sensors. The methods that he developed made it possible to create a new generation of nanomaterial-based sensors at industrially relevant scale. University of Toronto Shana is a world-renowned developer of technologies for diagnostics and therapeutic development. She is the co-founder of four life sciences startups including Arma Biosciences. Her > 250 scholarly publications have been cited > 25,000 time. Niklaus Schneeberger leads the business unit Active Implants & Microsystems at Helbling Technik Bern. Helbling Technik supports their clients in the engineering development of innovative products and technologies. Niklaus has earned a PhD in Physics at ETH Zurich developing infrared microsensors in CMOS technology and an MBA in management of technology from EPFL Lausanne. He has over 25 years of experience in technology and product development in the area of highly miniaturized sensors, medical devices and microsystem technology. Marion Badi works as project engineer in the Active Implants & Microsystems unit at Helbling Technik Bern. Helbling Technik supports their clients in the engineering development of innovative products and technologies. Marion earned a PhD in electrical engineering at EPFL working on the development of implantable electrical therapies targeting neurological injuries. She has expertise in diverse engineering areas such as electronics, modeling, and signal processing with a focus on biomedical applications. John de La Parra Periodic Table of Food Dr. John de la Parra is an ethnobotanist and plant chemist with expertise in food crops and medicinal plants. He is currently the President of the Society for Economic Botany. John is also Manager of the Global Food Portfolio at The Rockefeller Foundation where his work focuses on the management of the Periodic Table of Food Initiative, a global effort to create a public database of the biochemical composition and function of the food we eat using the latest mass spectrometry technologies and bioinformatics. He also holds appointments as an Associate at Harvard University and a Lecturer at Tufts University where his expertise encompasses ethnobotany, food system innovation, agriculture, and medicinal plants. He has held additional appointments as a Research Scientist at MIT and a Lecturer of Biotechnology at Northeastern University. Léa Montégut is a Ph.D. candidate in Pr. Guido Kroemer’s laboratory “Metabolism, cancer and Immunity”. She studied basic mathematics, physics and chemistry before she specialized in biology during her M. Sc. at École Polytechnique (France). She did her Master’s thesis at Columbia University (New York) in Pr. Gerard Ateshian’s Musculoskeletal Biomechanics Laboratory, working on 3D culture of cartilage implants. She then spent two years studying metabolic therapy for optimization of antibody production in Pr. Mario Jolicoeur’s laboratory of applied metabolomics in Polytechnique Montréal. She is now focusing on the role of ACBP, a metabolic factor which increases appetite and shifts lipids metabolism towards fat storage, in cancer development and treatment. - Appetite regulation - Metabolism modelling - Imaging flow cytometry - Breast cancer models Isabelle MARTINS received her Ph.D. from the University of Paris, France, in 2008. Her thesis focused on the pathological expression of MHC II molecules in melanomas. After her PhD, she joined the Gustave Roussy Institute as a post-doctoral fellow where she started studying the cellular and molecular mechanisms involved in the immunogenicity of cell death after chemotherapy (2008-2013). In 2017, she completed her post-doctoral training investigating the cell death processes involved in the elimination of cancer cells following exposure to ionizing radiation. She is currently a Senior Scientist in the laboratory “Metabolism, Cancer and Immunity” of Pr. Guido Kroemer, where she investigates several aspects of cell death, metabolism and cancer developing technological innovations. - Cell death - Metabolism obesity - Anti-tumour immunity Marine Fidelle is a PharmD level passionate about immunology. During her PhD (2018-2021) in Pr. Zitvogel’s lab, she managed to elucidate the vicious immunosuppressive mechanism of antibiotic treatments in patients receiving immunotherapy with immune checkpoint inhibitors (ICIs). She wants to explore therapeutic interventions to circumvent the deleterious impact of gut dysbiosis in patients with cancer. In the meantime, she has discovered a promising biomarker of ICIs response and prognosis. She is also implicated in a multicentric lung cancer screening programme. - Diet and Metabolism - Gut microbiome involvement in cancer - MultiOmics Analysis Guido Kroemer is currently Professor at the Faculty of Medicine of the University of Paris, Director of the research team "Metabolism, Cancer and Immunity" of the French Medical Research Council, Director of the Metabolomics and Cell Biology platforms of the Gustave Roussy Cancer Center, and Hospital Practitioner at the Hôpital Européen George Pompidou, Paris, France. Dr. Kroemer’s work focuses on the pathophysiological implications of cell stress and death in the context of aging, cancer and inflammation. He discovered the the cytoprotective and antiaging effects of macroautophagy, as well as the decisive role of immunogenic cell death in anticancer treatments. Prof. L. Zitvogel, MD (Clinical Oncology), PhD (Tumor Immunology), full professor at the University Paris Saclay, graduated in Medical Oncology in 1992. Scientific career first at the University of Pittsburgh, US. Became Research Director at Institut National de la Santé et Recherche Médicale U1015, and Scientific Director of the Clinicobiome program at Gustave Roussy, the largest cancer Center in Europe in 1998. Actively contributed to the field of cancer immunology and immunotherapy. Pionner of the concepts of immunogenic cell death and gut microbiota in cancer immunosurveillance and therapies. Recipient of many awards: French National Academy of Medicine, Translation Research INSERM Prize, the ASCO-SITC, Brupbacher Awards 2017, ESMO Immuno-Oncology Award 2017, Baillet Latour Prize 2019 and the Griffuel Prize 2019. Dr. Jonathan Pol is a permanent researcher at INSERM in Pr. Guido Kroemer’s team (Centre de Recherche des Cordeliers | Institut Gustave Roussy, France), where he leads a group in Immuno-Oncology. He obtained his PhD in Molecular and Medical Virology in 2008 (Paris, France). Then, he joined the teams of Drs. Brian Lichty and Yonghong Wan for 5 years at McMaster University (ON, Canada) to develop oncolytic cancer vaccines. In 2014, he returned to France in Pr. Kroemer’s laboratory to study cancer immunogenic cell death and immunosurveillance, and pursue the development of cancer immunotherapies. In particular, his work has demonstrated that caloric restriction mimetics stimulate cancer immunosurveillance and improve the efficacy of chemo-immunotherapy. Alumni at Laurence Zitvogel Lab Gladys FERRERE is a researcher and she studies the impact of microbiota and diet in different pathologies. In 2015, she obtained her pHD on the role of microbiota in liver disease. After she joined Zitvogel’s team at Gustave Roussy Institute. She showed the impact of ketogenic diet and the metabolites associated on the immunotherapies responses in preclinical models. In Clinicobiome program, a clinical trial named KETOREIN is open since november 2021 and tests the diet she found. She worksnow at the national Institute in food research and tries to find pro- or prebiotic that can improve people’s life. - Tumor immunology Santorio is committed to ensuring that your privacy is protected. That’s why we have taken the necessary steps to meet worldwide data privacy requirements, according to the EU General Data Protection Regulation and the laws of Switzerland, which regulate the storage, process, access, and transfer of personal data. Should we ask you to provide certain information by which you can be identified when using this Website, we will only collect it if you choose to give it to us. We do not share any of your personally identifiable information with third parties for their own marketing use unless you explicitly give us permission to do so. You can be assured that the collected personal information will only be used in accordance with this privacy statement. 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75th anniversary: Fleming Showcase Archive Exhibition About the exhibition In designing the programme for our 75th anniversary in 2020, we undertook research of the Microbiology Society’s early history at the Wellcome Collection in London, where the archives for the Society for General Microbiology (our original name) are held. From this research, we were lucky enough to uncover several items including letters and photographs that provide a unique insight and visual guide to the founding days of the Society. The aim of the founding members, which included Sir Alexander Fleming FRS and Marjory Stephenson FRS, was to bring together scientists working in different areas of microbiology to form a Society that would offer the benefits of interdisciplinary discussion and provide microbiologists with a common meeting ground. 75 years later, this aim remains central to our purpose. In producing this small exhibition, we have collaborated with Public Health England’s (PHE) National Collection of Type Cultures (NCTC) team, who kindly re-produced items relating to the work of Sir Alexander Fleming from their own archives. One of the founding members of the Society, Ralph St John- Brooks, was also the first curator of the National Collection of Type Cultures from 1920 until 1946. Public Health England's National Collection of Type Cultures The National Collection of Type Cultures itself is a repository and provider of a diverse range of authentic bacterial pathogens, medically relevant bacterial strains and bacteriophage. Established in 1920, NCTC is currently celebrating its centenary. Like the Microbiology Society, supporting a diverse scientific community of microbiologists and their collaborators remains central to its remit. The value of such a collection to microbiologists is well illustrated by Fleming’s use of it throughout his career; from acquiring strains to test and characterise the then newly discovered lysozyme in the 1920s, to depositing strains of contemporary biomedical interest such as NCTC 6571 (“The Oxford Staphylococcus”) which was used by Fleming during the penicillin trials of the 1940s. Through these strains’ use in research and their maintenance in the NCTC, the legacy and work of microbiologists past and present, including Sir Alexander Fleming, is preserved; and presented here today. We hope you enjoy this exhibition, alongside our Fleming Showcase which is dedicated to the legacy of Fleming Prize winners and aims to demonstrate the impact of both established and up-and-coming scientists in addressing important global challenges. Browse through images sourced from the Wellcome Collection's Society for General Microbiology archives. Browse through the National Collection of Type Cultures archives. Image credits:Wellcome Collection Society for General Microbiology Archives Public Health England Archives National Culture of Type Cultures

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Bertrand Jordan, Daniel Chan, Herb Heyneker, and Peter Lockey have all been appointed to the scientific advisory board of PamGene. The Den Bosch, Netherlands, microarray company said its board now includes eight members in areas such as oncology, infectious diseases, bioinformatics, genetics, pharmaceutical research and development, immunology, and proteomics. Jordan is a molecular biologist whose work focuses on large-scale transcript analyis and genomics research, and has been a director of research at France’s Centre Nationale de Recherches Scientifiques, or CNRS. Chan is a professor of pathol-ogy, oncology, urology and radiol-ogy at the John Hopkins University Medical School, director of clinical chemistry, Johns Hopkins Hospital, and director of the biomarker discovery center at Hopkins’ Sidney Kimmel Comprehensive Cancer Center. His research focuses on cancer proteomics, according to the Cancer Center website. Heyneker is a veteran in biotechnology R&D. After having served as the founding chief scientific officer of Genentech from 1976 to 1984, he joined the spinoff Genencor as vice president of R&D. He also founded Eos, a biotechnology company, and served as chief technology officer until the company was acquired by Protein Design Labs earlier this year. He now works as an advisor to Abingworth, a Palo Alto- and London- based venture capital firm. Lockey is director of biochemistry and high-throughput screening at Argenta Discovery of Harlow, Essex, UK. Prior to joining Argenta, he led teams in the high-throughput screening and assay development groups at Aventis UK. Peter Wagner, founder, senior vice president and CTO of Zyomyx, has been named one of the ten 2004 technology pioneers by the World Economic Forum. Wagner has been selected for leadership and “innovative research” in the protein biochip technology field. This technology pioneers program was established in 2000 to identify and integrate companies involved in designing and developing new technologies, to monitor and highlight the innovations, and to explore “possible societal repercussions,” according to the WEF. “I am honored to have been selected by the World Economic Forum, and I look forward to contributing to the technology pioneers community as a member of this distinguished group,” stated Wagner. “I am very proud of the accomplishments Zyomyx has made to the fields of proteomics and bionanotechnology, including this year’s launch of the first automated protein profiling biochip system.” Kenneth Weisshar has been elected to the board of directors of Digene, the Gaithersburg, Md., company said last week. Weisshar served as chief operating officer and strategy advisor of Sensatex/Life Link from 2000 to 2003. Before joining Sensatex, he held a number of senior positions at Becton, Dickinson & Company, including chief financial officer; president, worldwide consumer health care; sector president, bioscience cell analysis; president BD division; and vice president corporate planning and development. From 1982 to 1988 he was a consultant at McKinsey & Company, and was employed by Raychem Corporation between 1974 and 1982.

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The transition from a-helix to random coil of the titrating polyamino acid Co-poly-L-(lysine, phenylalanine), (p-(Lys,Phe)), has been investigated as a function of pH and ionic strength in aqueous solution and at the air water interface by means of circular dichroism (CD) spectroscopy and the Langmuir surface film balance technique. The results strongly suggest that the helix-coil transition for peptides at the air-water interface can be determined by using the two-dimensional Flory exponent, v, to express the pH dependent peptide surface conformation. The helix-coil titration curve of p-(Lys,Phe) shifts approximately 2.5 pH units towards lower pH at the air-water interface, as compared with the bulk solution. This finding is of relevance for the understanding of conformation and conformational changes of membrane-tran sporting and membrane penetrating peptides as well as for the use of peptides in molecular devices. (c) 2005 Elsevier B.V All rights reserved. Subject classification (UKÄ) - Physical Chemistry

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Scientific topics: Pathway or network Difficulty level: Not specified Contributors: Dr. Alexander Lex Alexander Lex (http://alexander-lex.com/) talks about enRoute, a tool for dynamic path extraction from biological pathway maps for in-depth experimental data analysis. He highlights the inherent problem with correlating real-life heterogeneous data to pathways, namely that they rarely follow the...

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Computational Techniques in the Drug Design Process Computational Techniques in the Drug Design Process Cytoclonal Pharmaceutics Inc. The purpose of this document is to outline the drug design process and specifically the role of computational modeling techniques. This is not meant to be a comprehensive review. It is meant to list the most important techniques currently in use. The process of designing a new drug and bringing it to market is very complex. According to a 1997 government report, it takes 12 years and 350 million dollars for the average new drug to go from the research laboratory to patient use. Pieces of this process are often repeated to create successively better drugs for the same condition. In the case of antibiotics, drugs loose effectiveness as an immunity is built up, thus leading to a continuing "arms race". The major steps in the drug design process "from scratch" are. FIND WHAT IS KNOWN Find out all that is known about the disease and existing or traditional remedies. It is also important to look at very similar afflictions and their DEVELOP AN ASSAY Develop an assay technique to test drug effectiveness. An ideal assay is one in which a compound can be added to tissue samples or micro-organism colonies and there will be a visible indication of an effective treatment. At worst, there must be a way to test the drug on a laboratory animal that is susceptible to the disease. If the only way to test the effectiveness of a trial compound is to inject an untested compound into a human subject then there is no way to proceed in finding a pharmaceutical Steps 4 and 5 of this procedure are often performed simultaneously. CONSIDER FINANCIAL ISSUES The next step is to make a financial decision about whether to proceed with the development process. The assay technique will determine the cost of testing compounds. If there are existing chemical treatments, it will be a refinement effort which saves the expense of finding lead compounds. All drugs must go through extensive testing so this is a fairly fixed cost. There may be governmental grants or tax incentives associated with certain diseases. The number of patients requiring treatment and merits of existing treatments will determine the long term profitability of producing a drug. FIND LEAD COMPOUNDS Lead compounds are compounds that have some activity against a disease. These may be only marginally useful and may have severe side effects. However, the lead compounds provide a starting point for refinement of the chemical structures. Lead compounds may come from many sources, including - The isolation of active compounds from traditional remedies. - The testing of natural materials followed by an isolation - Drugs effective against similar diseases. - Use of combinatorial chemistry techniques which produce large numbers of related chemical compounds. This allows testing a large number of compounds at once. When a mixture that is useful is found, a separation must be done to determine which of the related structures has some drug activity. This has been one of the most promising and rapidly growing techniques in - Searching chemical databases to find compounds similar to those found by the above means. This is the only part of the lead finding process that is considered to be a computational technique. There are many different measures of molecular similarity and ways of efficiently handling large databases, so this is not yet a trivial step. ISOLATE THE MOLECULAR BASIS FOR THE DISEASE If it is known that a drug must bind to a particular spot on a particular protein or nucleotide then a drug can be tailor made to bind at that site. This is often modeled computationally using any of several different techniques. Traditionally, the primary way of determining what compounds would be tested computationally was provided by the researchers' understanding of molecular interactions. A second method is the brute force testing of large numbers of compounds from a database of available structures. More recently a set of techniques, called rational drug design techniques or De Novo techniques have been used. These techniques attempt to reproduce the researchers' understanding of how to choose likely compounds built into a software package that is capable of modeling a very large number of compounds in an automated way. Many different algorithms have been used for this type of testing, many of which were adapted from artificial intelligence applications. No clear standard has yet emerged in this area so it is impossible to say what is best the best technique at this time. These techniques have seen quite a bit of active development in recent years. Unfortunately, the complexity of biological systems makes it very difficult to determine the structures of large biomolecules. Ideally a x-ray chrystallography structure is desired, but biomolecules are very difficult to chrystalize. Another very useful technique, called "distance geometry" is to find some of the internuclear distances using NMR Nuclear Overhauser Effect experiments then find molecular geometries that have these distances. If only a protein sequence is known, there are many techniques for predicting how that protein will fold, but none has yet been shown to be 100% reliable. Even once a structure has been determined, identifying the site where a drug must bind is not a trivial task. The difficulty in find geometries makes it possible to bring first generation drugs to market by refinement of lead compounds without ever knowing the target site for the drug in the body. As such, these techniques are being used primarily for designing improved treatments for diseases that have already been characterized extensively. REFINE DRUG ACTIVITY Once a number of lead compounds have been found, computational and laboratory techniques have been very successful in refining the molecular structures to give a greater drug activity and fewer side effects. This is done both in the laboratory and computationally by examining the molecular structures to determine which aspects are responsible for both the drug activity and the Synthetically, functional groups are removed in order to find out which must be present to give a useful drug and which are not necessary. The back bone of the structure is made more flexible or more rigid. A rigid back bone may hold the functional groups in the exact alignment necessary for the drug to bind. A flexible back bone may be necessary to allow the drug to get into the binding site. Adding bulky groups at other points on the molecule is often done in the hopes that these new groups may hinder the molecule from binding at unwanted sites which are responsible for the side effects. Computationally, the technique used is known as QSAR (Quantitative Structure Activity Relationships). It consists of computing every possible number that can describe a molecule then doing an enormous curve fit to find out which aspects of the molecule correlate well with the drug activity or side effect severity. This information can then be used to suggest new chemical modifications for synthesis and testing. Another important aspect of the molecular structure is its solubility. Whether the molecule is water soluble or readily soluble in fatty tissue will affect what part of the body it becomes concentrated in. The ability to get a drug to the correct part of the body is an important factor in Ideally there is a continual exchange of information between the researchers doing QSAR studies, synthesis and testing. These techniques are frequently used and often very successful since they do not rely on knowning the biological basis of the disease which can be very difficult to determine. Once a drug has been shown to be effective by an initial assay technique, much more testing must be done before it can be given to human patients. Animal testing is the primary type of testing at this stage. The scientists doing the testing must be particularly observant of many little details since this is where unexpected side effects can be found. Another question to be answered is whether the drug will work well or poorly with other drugs. This is also where initial data necessary to determine correct dosages Eventually, the compounds which are deemed suitable at this stage are sent on to clinical trials. In the clinical trials, additional side effects may be found and human dosages are determined. The typical testing process goes like this. - Preclinical testing in animals and test tubes. This takes an average of 6.5 years. Only one compound in 1000 is sent on to clinical testing. - Phase I clinical trials in a few human volunteers. This typically takes a year and a half. Seventy percent of the compounds are sent on to the next step. This is primarily a safety test. - Phase II clinical trials in a few hundred patients. This takes two years and a third of the compounds are passed on to the next step. This is further safety testing and an initial examination of the ability of the drug to have the intended effect in humans. - Phase III clinical trials in a few thousand patients. This step collects more data on safety, dosage, drug activity and side effects. About a quarter of the compounds pass this phase. - An advisory panel of doctors reviews the data and makes recommendations to the FDA. - FDA approval or rejection. - The FDA continues to monitor drug performance long after approval has Before a drug can be produced, there must be a means to administer it. Ideally, a tasteless or bland tablet can be created. Alternatively, an oral liquid, intravenous injection or directly applied cream may be Tablets are created by adding other compounds to minimize stomach upset and control timed release of the drug. A tablet may also have a compound which is a matrix that helps it hold it's shape without crumbling into a powder. Oral liquids are often combined with strong flavors and alcohol to mask the taste of the drug and prevent throat irritation. A cream may have to be thickened or have a component that the skin will The large scale production of complex molecules can be very difficult. Compounds originally isolated from natural products may continue to be harvested. Often natural products are found in nature only in extremely small quantities necessitating a complex synthesis. One route that has been under development more recently is to have compounds produced by genetically engineered micro-organisms or plants. Drugs have a high value per gram. As such production techniques can be viable even though they are far more inefficient than those used by bulk chemical producers. Often all possible production techniques are researched even though only one will be put into practice. This is done so that there are no openings for competing corporations to get around a manufacturers patents by using a different technique. Manufacturing regulations have become much more stringent in recent years. It is now also important to determine what by-products will result from production and what environmental impact there will be. It is possible to have a case in which a less efficient manufacturing process is more profitable due to the value of side products and reduced waste disposal If there is only one available treatment for a disease, it is only necessary to see that physicians know about it. If there are several competing treatments, there may be quite a bit of marketing done so that physicians will understand the relative merits of each. After a large amount of experience under a physicians supervision, a drug may be approved for over-the-counter sales. This is often the biggest profit making end of the pharmaceutical industry. Once the chemical patents have expired, a drug can be produced by any manufacturer. Generic drugs are often less expensive for the consumer and yield a low profit margin for the producer. The production of generic drugs favors the most cost effective production process. A good book over all, and chapter 7 in particular, is G. L. Patrick "An Introduction to Medicinal Chemistry" Oxford (1995) A recent review is L. M. Balbes, S. W. Mascarella and D. B. Boyd, in "Reviews in Computational Chemistry, Vol. 5" K. B. Lipkowitz, D. B. Boyd, Eds., VCH, 337 (1994) An introduction to computational techniques is G. H. Grant, W. G. Richards "Computational Chemistry" Oxford (1995) A more detailed description of computational techniques is A. R. Leach "Molecular Modelling Principles and Applications" Longman (1996) L. Balbes' "Guide to Rational (Computer-aided) Drug Design" is at There are many links on Soaring Bear's web page at An introduction to structure-based techniques is I. D. Kuntz, E. C. Meng, B. K. Shoichet Acct. Chem. Res. 27 (5), 117 (1994) An introduction to De Novo techniques is S. Borman Chemical and Engineering News 70 (12), 18 (1992) There is more information about clinical testing at An expanded version of this article will be published in "Computational Chemistry: A Practical Guide for Applying Techniques to Real World Problems" by David Young, which will be available from John Wiley & Sons in the spring of 2001. Return to table of contents.

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Our TREMOR TRACKER App Our app, TremorTracker(tm), began as an effort to help our friends with Essential Tremor, gait disorders, and anyone suffering from a motor disorder, to easily self-monitor their symptoms. If desired, the app can provide neurologists or neurosurgeons with accurate accessory data derived from a well-defined behavioral context, which can enhance understanding of symptom fluctuations and treatment efficacy when paired with clinical data and clinician judgment. We are currently investigating the use of TremorTracker(tm) in individuals suffering from Essential Tremor and treated with Deep Brain Stimulation, in partnership with Neurosurgeons in the Allegheny Health Network. The TremorTracker(tm) app is built around the motion and other sensors available in common consumer products and will incorporate auxiliary biometric and environmental sensors to form a flexible scientific measurement platform, with ease of use, behavioral scientific rigor, and interoperability with advanced data science applications as core design principles.

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Family Resilience Research Project The Family Resilience Research Project explores how a parental cancer diagnosis affects family functioning over the course of a year. The primary aim is to identify what characteristics, attitudes, and behaviours help families to maintain or restore healthy family functioning and individual mental health outcomes during this time. The results of this research will help us to understand the characteristics of families that may require extra support in the future and determine what support will help families in this position. We are looking for families to participate in this research. Specifically: - parents diagnosed with cancer in the last nine months who have children aged 8-25 - their partner (if applicable and willing) - their children aged 12-25 (if applicable and willing) If you decide to participate, you will be asked to fill out three surveys online or on paper (your choice). One now, one in 6 months, and one in 12 months. Each survey will ask about the cancer, your family, and your feelings. After the second survey, you will be asked about your willingness to participate in a phone interview. You can decide then whether you want to or not.

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What is Sudden Cardiac Arrest? SCA Fact Sheet What is an AED and how do they work?? Find out here: AED Fact Sheet What can you do to prevent SCA?? Preventing SCA Fact sheet Is a heart attack the same as a sudden cardiac arrest?? NO!!! A heart attack is a plumbing problem. Sudden cardiac arrest is an electrical problem. A heart attack can cause sudden cardiac arrest. Read more here: SCA vs Heart Attack Fact Sheet HeartSafe Communities http://heartsafe-community.org This is an excellent produced by Coon Rapids HeartSafe demonstrating CPR and AED use. Be the help!!! Heart Failure – What is it and what does it have to do with SCA?? Heart Failure Fact Sheet What is your Ejection Fraction and what does it have to do with SCA? EF Fact sheet What is an Implantible Cardioverter Defibrillator (ICD) and what does it have to do with SCA?? ICD Fact sheet Other links to partners and resources: Sudden Cardiac Arrest Association – www.suddencardiacarrest.org The Sudden Cardiac Arrest Association is a national network of SCA Survivors. Provides information about SCA, its prevention and treatment, AED programs, educational tools, medical guidelines, and more. Medtronic Foundation Survive SCA – www.heartrescueproject.com The Medtronic HeartRescue Project is a collaborative effort to increase sudden cardiac arrest (SCA) survival rates. CARE Foundation – www.longqt.org The Cardiac Arrhythmias Research and Education Foundation. Dedicated to providing funding for research and increasing awareness of unexpected sudden cardiac death due to acquired heart disease and inherited rhythm disorders. Hypertrophic Cardiomyopathy Association – www.4hcm.org Provides information, support and advocacy related to hypertrophic cardiomyopathy. SADS Foundation – www.sads.org Sudden Arrhythmia Death Syndrome Foundation website. Mission is to save the lives and support the families of children and young adults who are genetically predisposed to sudden death due to heart rhythm abnormalities.

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It has been recognized that the development of new therapeutic drugs is a complex and expensive process. A large number of factors affect the activity in vivo of putative candidate molecules and the propensity for causing adverse and toxic effects is recognized as one of the major hurdles behind the current “target-rich, lead-poor” scenario. Structure-Activity Relationship (SAR) studies, using relational Machine Learning (ML) algorithms, have already been shown to be very useful in the complex process of rational drug design. Despite the ML successes, human expertise is still of the utmost importance in the drug development process. An iterative process and tight integration between the models developed by ML algorithms and the know-how of medicinal chemistry experts would be a very useful symbiotic approach. In this paper we describe a software tool that achieves that goal - iLogCHEM. The tool allows the use of Relational Learners in the task of identifying molecules or molecular fragments with potential to produce toxic effects, and thus help in stream-lining drug design in silico. It also allows the expert to guide the search for useful molecules without the need to know the details of the algorithms used. The models produced by the algorithms may be visualized using a graphical interface, that is of common use amongst researchers in structural biology and medicinal chemistry. The graphical interface enables the expert to provide feedback to the learning system. The developed tool has also facilities to handle the similarity bias typical of large chemical databases. For that purpose the user can filter out similar compounds when assembling a data set. Additionally, we propose ways of providing background knowledge for Relational Learners using the results of Graph Mining algorithms. © 2011 The Author(s). Published by Journal of Integrative Bioinformatics. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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Established in 2003 the UC Davis Genome Center uses state-of-art-technologies to understand how the heritable genetic information of diverse organisms function in health and disease. Genomic studies are revolutionizing biology and the Genome Center is at the forefront of this revolution. We are home to an internationally renowned faculty whose research interests exploit cutting-edge technologies for generating and interpreting vast amounts of data at all levels, from genes to entire organisms and populations. Innovative experimental science interfaces with the latest in computer capabilities to generate advances in basic biology, agriculture, human and veterinary medicine, biomedical engineering, and computer science. The diversity of organisms studied at UC Davis is one of its biggest strengths. The Genome Center bolsters this strength by providing -omics technologies on an at-cost, as-needed basis to all Davis faculty through its service cores that specialize in bioinformatics, DNA and expression analysis, metabolomics, proteomics, TILLING, and yeast one hybrid services. Through collaborations and access to the enabling technology cores, the Genome Center serves the basic and translational research needs of all UC Davis faculty whose studies encompass human and animal diseases, food and biofuel crops, biodiversity and environmental health, as well as hitherto little-studied or unknown organisms. These discoveries provide the raw information that is being translated into advances in medicine, agriculture, and the sustainability of our global society. The UC Davis Genome Center aims to have a welcoming, inclusive, and equitable environment in which to conduct -omics research. The Genome Center supports the diversity, equity, and inclusion initiatives on the UC Davis campus and is increasing existing efforts in recruitment and retention of faculty, staff, and students working in -omics from historically under-represented communities. - The Genome Center is committed to fostering a supportive environment to learn, work, and conduct research; - creating a diverse community via recruitment efforts as well as social and educational events; - encouraging outreach to promote an interest in -omics and science literacy, particularly to communities historically under-represented in STEM fields; - conducting inclusive -omics research to improve health and the environment for all communities.

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Biotechnology is a field of study of applied biology that engages the use of living organisms and bioprocesses in technology, medicine, engineering, and other fields necessitating biological items. The following are biotech firms and/or biotech consulting firms that have been participating on pharmaceuticals study and medicine items. Most of them are recognized as a biotech consulting firms as properly. Amgen Inc. (NASDAQ: AMGN, SEHK: 4332) is among biotech corporations that are extensively known worldwide headquartered in Thousand Oaks, California. Amgen is the international top self-governing biotech firm and is broadly regarded amongst the most prominent in the biotechnology business. Genetic Engineering Technologies, Inc., (Genentech Inc.), is a biotech corporation, established in 1976 by venture capitalist Robert A. It is believed to have established the biotechnology sector. Additionally, the corporation is viewed as to be a lead the way in the field of recombinant DNA technology, in regard with restriction enzymes, successfully express a human gene in bacteria and contributed to its results with synthetic human insulin in 1978. NASDAQ: GENZ (Genzyme Corporation) an American biotech business located in Cambridge, Massachusetts. The institute focuses on establishing tough study facilities for its students, train them to develop into specialist contributors in their fields, in manufacturing or in academic institutions. Union Chimique Belge (UCB) is a biopharmaceutical manufacturer primarily based in Brussels, Belgium. At initially focused on industrial chemical compounds, the enterprise also incorporated a minute pharmaceutical sections situated about Meurice Laboratories. In the early 1950s, UCB established a investigation centre where new medicines like hydroxyzine (Atarax) were developed. NASDAQ: GILD (Gilead Sciences) is a biopharmaceutical organization that discovered out, develops and traded therapeutics. The firm has focused principally on antiviral drugs to remedy individuals contaminated with hepatitis B, influenza or HIV. Serono S.A. is a biotechnology firm primarily based in Geneva, Switzerland. A principal pace in its progress was the invention of a technique of extracting urinary gonadotropins. The organization also performs analysis in autoimmune ailments and oncology. high throughput sequencing : BIIB. (Biogen Idec, Inc) is a biotechnology corporation dedicating itself to medicines for cancer, autoimmune mess and neurological chaos. CSL Restricted is an Australia headquartered producer of healthcare products. Its manufacturing items comprise a wide variety of blood plasma derivatives, vaccines, and cell culture reagents utilised in a variety of health-related and hereditary researches and industrial relevance. NASDAQ: CEPH (Cephalon, Inc.) is a U.S. biopharmaceutical corporation co-established in 1987 by Dr. Frank Baldino, Jr., The Company’s is named immediately after the adjective “cephalic” which indicates “connected to the head/brain,” and it was recognized mostly to pursue healing for neurodegenerative connected illnesses.

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It sounds like something out of the Borg in Star Trek. Nano-sized robots self-assemble to form biological machines that do the work that keeps one alive. And yet something like this really does go on. Every cell in our body – be they flesh and blood, brain and everything in between – has identical DNA, the twisted staircase of nucleic acids uniquely coded to each organism. Complex assemblages that resemble molecular machines take pieces of DNA called genes and make a brain cell when needed, instead of, say, a bone cell. These molecular machines are so complex, yet so tiny, that scientists today are just starting to understand their structure and function using the latest microscopes and supercomputers. Biological molecular machines could lay the foundation for developing cures to diseases like cancer. How small can one see, and what will one find? Cryo-electron microscopy combined with supercomputer simulations have created the best model yet, with near atomic-level detail, of a vital molecular machine, the human pre-initiation complex (PIC). A science team from Northwestern University, Berkeley National Laboratory, Georgia State University, and UC Berkeley published their results on the PIC May 2016 in the journal Nature. “For the first time, structures have been detailed of the complex groups of molecules that open up human DNA,” said study co-author Ivaylo Ivanov, associate professor of chemistry at Georgia State University. Ivanov led the computational work that modeled the atoms of the different proteins that act like cogs of the PIC molecular machine. The PIC finds genes associated with making a specific protein, such as an antibody or an enzyme. There the PIC pulls apart the two strands of DNA and feeds the coding strand to the workhorse enzyme RNA polymerase II. This starts transcription, where DNA bits are copied by RNA polymerase II into a single strand of messenger RNA. The RNA makes its way to ‘protein factories’ in the cell called ribosomes that take them as orders for which protein to make. If DNA is like the blueprint of a new house, RNAs are instructions to the ‘contractors’ at the ribosome work station. The manufactured proteins are like the nails, wood, plaster, and just about everything else in the house. The experiment began with images painstakingly taken of PIC. They were made by a group led by study co-author Eva Nogales, a professor in the Department of Molecular and Cellular Biology at UC Berkeley and also Senior Faculty Scientist at the Lawrence Berkeley National Laboratory and Howard Hughes Medical Investigator. Nogales’ group used cryo-electron microscopy (cryo-EM), a rising star in lab techniques. They cryogenically froze human PIC bound to DNA. The freezing kept it in a chemically-active, near-natural environment. Next they zapped it with electron beams. Thanks to recent advances in direct electron detector technology, cryo-EM can now image at near atomic resolution large and complicated biological structures that have proven too difficult to crystalize. The go-to technique, X-ray crystallography, requires crystallized specimens, and cryo-EM avoids this hard step. Over 1.4 million cryo-EM ‘freeze frames’ of PIC were processed using supercomputers at the National Energy Research for Scientific Computing Center to sift out background noise and reconstructed three-dimensional density maps that show details in the shape of the molecule that had never been seen before. “Cryo-EM is going through a great expansion as are all the computer software used to generate both the density maps and also to interpret them like we’ve done in this study,” Nogales said. “It is allowing us to get higher resolution of more structures in different states so that we can describe not just one picture of how they look, but several pictures showing how they are moving. We don’t see a continuum, but we see snapshots through the process of action.” Study scientists next built an accurate model that made physical sense of the density maps of PIC using XSEDE, the eXtream Science and Engineering Discovery Environment, funded by the National Science Foundation. XSEDE allows scientists to interactively share computing resources, data and expertise via a single virtual system. Ivaylo Ivanov’s team has run over four million core hours of simulations on the Stampede supercomputer at the Texas Advanced Computing Center to model complex molecular machines, including those for this study. Ivanov’s broader molecular machine work also includes an XSEDE allocation of 1.7 million core hours on the Comet supercomputer at the San Diego Supercomputing Center. “I have been using XSEDE resources for more than 12 years now,” Ivanov said. “Without the availability of XSEDE resources, all of our research would have been much more limited in terms of the systems that we can address. For us, XSEDE has been absolutely essential.” The goal of all this computational effort is to produce atomic models that tell the full story of the structure and function of the protein complex of molecules. To get there Ivanov’s team took the twelve components of the PIC assembly and created homology models for each component that accounted for their amino acid sequences and their relation to similar known protein 3-D structures. Next they approximated the experimental densities Nogales’ team found onto a grid. “We can use a method called molecular dynamics flexible fitting,” explained Ivanov, “where you essentially run a molecular dynamics simulation. And you use the experimental density to bias the atoms in the molecular dynamics simulation to move into the denser regions of the EM map. That’s the process of flexible fitting to the EM map.” They refined the model with the Phoenix crystallographic refinement package. “That is a complimentary technique that allows us to position side chains and improve the model so that we can capture all the details that are present in the density map,” Ivanov said. XSEDE was “absolutely necessary” for this modeling, said Ivanov. “When we include water and counter ions in addition to the PIC complex in a molecular dynamics simulation box, we get the simulation system size of over a million atoms. One cannot run that on a work station or even on a modest cluster. For that we really need to go to a thousand cores. In this case, we went up to two thousand and forty-eight cores. And for that we needed access to Stampede,” Ivanov said. One of the insights gained in the study is a working model of how PIC opens the otherwise stable DNA double helix for transcription. Nogales explained that one could imagine a cord made of two threads twisted around each other. Hold one end very tightly. Grab the other and twist it in the opposite direction of the threading to unravel the cord. That’s basically how the living machines that keep us alive do it. “The DNA needs to be opened and moved into the polymerase active site to encode for the first RNA nucleotide,” explained Nogales. “The pre-initiation complex is holding the two strands of the DNA very tightly together at one end, so that they cannot move and they cannot open. On the other side of the PIC there is a machine that uses energy to push the DNA, twisting it in the opposite direction in which the two strands are threaded. And when this happens, in between the two sides, the strands will open,” said Nogales. This study resolved the structure of that molecular machine that acts like the twisting fingers, the transcription factor component TFIIH. “TFIIH has a translocase sub-unit, whose role is to simultaneously push the DNA toward the active site of the polymerase and unwind the DNA. By the combined pushing and unwinding, effectively you are separating the two strands of the DNA,” Ivanov said. Both scientists said that they are just beginning to get an atomic-level understanding of transcription, crucial to gene expression and ultimately disease. “Many disease states come about because there are errors in how much a certain gene is being read and how much a certain protein with a certain activity in the cell is present,” Nogales said. “Those disease states could be due to excess production of the protein, or conversely not enough. It is very important to understand the molecular process that regulates this production so that we can understand the disease state.” “This work illustrates well two general principles that will drive science in the next few years,” commented Peter Preusch, program officer with the National Institutes of Health (NIH). “One is the application of hybrid methods – combinations of biophysical methods including x-ray crystallography and cryoEM along with large scale computational methods to integrate information on larger molecular complexes. Two, there’s the requirement for team science drawing the expertise of multiple investigators to solve problems that cannot be tackled by any single lab working alone.” Peter Preusch is the Biophysics Branch Chief, Cell Biology and Biophysics Division, National Institute of General Medical Sciences, NIH. While this fundamental work does not directly produce cures, it does lay the foundation to help develop them in the future, said Ivanov. “In order to understand disease, we have to understand how these complexes function in the first place… A collaboration between computational modelers and experimental structural biologists could be very fruitful in the future. “ The May 2016 Nature Articles study (DOI: 10.1038/nature17970), “Near-atomic resolution visualization of human transcription promoter opening,” was authored by Yuan He, Lawrence Berkeley National Laboratory and now at Northwestern University; Chunli Yan and Ivaylo Ivanov, Georgia State University; Jie Fang, Carla Inouye, Robert Tjian, Eva Nogales, UC Berkeley. Funding came from the National Institute of General Medical Sciences (NIH) and the National Science Foundation.

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Domain-Decomposition Parallelization for Molecular Dynamics Algorithm with Short-Ranged Potentials on Epiphany Architecture Many-core processor architecture is a promising paradigm for the development of modern supercomputers. In this paper, we consider the parallel implementation of the generic molecular dynamics algorithm for the many-core Epiphany architecture. This architecture implements a new type of many-core processor composed of 16 simple cores connected by a network on chip with mesh topology. New approaches to parallel programming are required to deploy this processor. We use LAMMPS running on one 64-bit ARMv8 Cortex-A53 CPU core for comparing the accuracy of the results of the presented variant of the molecular dynamics algorithm for Epiphany and its computational efficiency.

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Long time Biostar Contributor Mary has compiled a beautiful summary of the current encode related news on the OpenHelix blog: See it at Encode floods the news networks While we are at it we will also reference the ENCODE project page and their video: Here is the compilation of major news releases related for the ENCODE project: MSNBC (USA) — New DNA project shows us living beyond our genes The Guardian (UK) — Breakthrough study overturns theory of ‘junk DNA’ in genome BBC (UK) — Detailed map of genome function The Globe and Mail (Canada) — Worldwide group of scientists solve ‘junk DNA’ mystery Toronto Star (Canada) — Massive DNA project shows human genome far from being just junk The Scientist — Getting to know the genome Source - Sept 6th, 2012 Oh, thanks for highlighting it. At first it was just a place for me to keep stuff I needed to monitor--and then I realized others might find it useful as well. I have a follow-up post on responses to the media as well. ENCODE waves hit the shore…and scientists respond I'll keep updating that as posts come in as well. Login before adding your answer. Use of this site constitutes acceptance of our User Agreement and Privacy

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Countries should really move up their do the job on genomic technologies to beat disorders, and share that technologies a lot more quickly with building nations, a new WHO report argued Tuesday. Genomics—the review of DNA sequences and gene functions—could make a huge contribution to improving upon human wellbeing, claimed the Planet Well being Organization’s Science Council. “Genomic technologies are driving some of the most ground-breaking exploration happening currently,” claimed WHO chief scientist Soumya Swaminathan. “The gains of these equipment will not be absolutely realised until they are deployed worldwide.” The report bundled a collection of suggestions designed to aid make that transpire. Genomics is the review of the full or component of the genetic sequence information and facts of organisms and makes an attempt to have an understanding of the construction and operate of all those sequences. Its supporters hope it will provide efficient, expense-efficient and sturdy usually means of blocking, diagnosing and managing main health conditions. The Science Council was set up in April last year to recommend WHO main Tedros Adhanom Ghebreyesus on advances in science and technologies that could directly strengthen international health and fitness. Designed up of 9 leading researchers and community health and fitness experts, it is chaired by Professor Harold Varmus, a 1989 Nobel laureate and a former director of the US Countrywide Institutes of Health and fitness. The council chose to target on genomics simply because of its successes in confronting infectious illnesses, cancers, and other long-term illnesses. Genomics makes use of biochemistry, genetics, and molecular biology to understand and use organic details in DNA and RNA, with benefits for medicine and general public health and fitness. “Genomics can make great contributions to human wellness, from surveying populations for infectious brokers, such as the virus that brings about COVID-19, to predicting and dealing with a extensive selection of ailments, these types of as cancers and developmental issues,” explained Varmus. Genome sequencing info became the foundation of world wide checking of both of those how the SARS-CoV-2 virus was evolving, and the emergence of new COVID variants. It was also employed in the advancement of vaccines. Bringing down prices It is not ethically or scientifically justifiable for considerably less nicely-resourced international locations to obtain accessibility to this kind of technologies extended just after wealthy nations do, the council’s report argued. It advocated expanded access to genomic technologies—particularly outside the house the richest countries—by addressing shortfalls in funding, laboratory infrastructure, materials, and remarkably qualified staff. The charges of setting up and growing genomic systems had been declining, said the report—but they could be brought down even further. Tiered pricing, shared intellectual home legal rights and investing revenue from a single space into a different could all enable make genomic systems additional reasonably priced, it argued. Ministries must collaborate with scientific organisations on working with genomics, constructing specialized ability and pooling assets with some others, the report included. But it also claimed that oversight and adherence to worldwide benchmarks was significant in selling the ethical and legal use of information received with genomic procedures. Inadequate sequencing of SARS-CoV-2 variants impedes world-wide reaction to COVID-19 © 2022 AFP WHO launches contact to pace up genomics tech advancement (2022, July 12) retrieved 14 July 2022 This document is issue to copyright. Aside from any fair dealing for the goal of non-public review or exploration, no aspect may well be reproduced with no the written authorization. The articles is offered for facts purposes only.

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Posted: October 2nd, 2017 Health Care is a universal profession and inevitably the health care worker will come in contact with people from diverse religions and diverse religious faiths. Health worker is supposed to be neutral towards the patients believes and he should work with the same compassion and care irrespective of the faith of the person. Health care worker should remain adaptable to the diverse faiths existing in the society. The current write-up is a critical consideration of the ethics and view points as provided by Christianity and Buddhism for the George’s case. The discussion proceeds with a comparative analysis of the views and the possible actions suggested by Christianity and the Buddhism. After the critical evaluation of the world views from the said two faiths, there is personal reflection presented in the context from my own believes and interpretation of righteousness (Entwistle, 2015). Amyotrophic lateral sclerosis George is an accomplished legal professional and is at present in his mid-fifties. In a recent minor accident he met in the playground and by subsequent diagnosis, he is found to possess AMS (Amyotrophic lateral sclerosis). It is a dangerous disease with progressive degradation traits of the brain nerves and the spinal cord. It will progressively will cause motor deterioration and the muscle atrophy will be caused to point of complete muscle control loss to the patients. Generally it is expected that patients with this disease will live not more than 3 to 5 years and in extremely uncommon cases, they can live up to 10 years. The victims will lose their ability to speak, move, eat and breathe progressively. Place an order in 3 easy steps. Takes less than 5 mins.

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May’s Continuous Medical Corps Symposium Lecture – Dr. Dale Smith Presenting The History of the Medical Corps After having our Medical Corps Symposium cancelled numerous times due to COVID, we decided to just transition to a continuous, online symposium where we present one talk each month that you can view live or watch recorded. Here is a message about May’s talk: Our 2021 Continuous Medical Corps Symposium has kicked off! Please disseminate the flyer and encourage maximum viewing of Dr. Dale Smith’s lecture on the History of the Navy Medical Corps: We will be hosting a live Q&A session with Dr. Smith on Microsoft Teams at 1200 EST on 05 May. The video can be viewed at https://youtu.be/j4wHwJezFKA. Please encourage maximum participation in the live event as it will be one of the last events for Dr. Smith before he retires. For any questions, please contact LCDR Jennifer Eng-Kulawy (contact in the global). Jennifer Eng-Kulawy, MD LCDR, MC, USN Medical Corps Liaison Officer Office of the Corps Chiefs (M00C1) Diplomate, American Board of Pediatrics, General Pediatrics and Pediatric Hospital Medicine Bureau of Medicine and Surgery 7700 Arlington Blvd Falls Church, VA 22042-5135 Bookmark the Medical Corps Chief’s Office Webpage and stay current! Follow our new public website at https://www.med.navy.mil/Pages/MedicalCorps.aspx! Follow us on Twitter, Medical Corps Chiefs Office @navy_physician for up to date information, career information and highlights within our Corps!

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BIOMATH FORUM - International Conferences on Mathematical. Biomathematics. As the study of biological systems becomes more quantitative, the part that mathematical analysis plays increases. This extends from the macroscopic, such as modelling the spread of a disease through a community, to the microscopic, such as determining the three-dimensional structure of proteins from knowledge of their sequence of amino acids. Research Interests. Nonlinear. Interview with Christina Cobbold (Glasgow) on what it’s like to research in biomathematics. Recorded as part of a Meet the Mathematicians event event at the Royal Society of Edinburgh. MTM is run the by Universities of Southampton and Manchester. It is funded by the UK’s Engineering and Physical Sciences Research Council. Related Links. Meet the Mathematicians Meet the Mathematicians is an. The Journal of Mathematical Biology focuses on mathematical biology - work that uses mathematical approaches to gain biological understanding or explain biological phenomena. Papers should either provide biological insight as a result of mathematical analysis or identify and open up challenging new types of mathematical problems that derive from biological knowledge (in the form of data, or. BIOMATHEMATICS Free Undergraduate Project Topics And Research Materials, Free Undergraduate Project Topics, Research Materials, Education project topics, Economics project topics, computer science project topics, Hire a data analyst. This book on modelling and simulation in biomathematics will be invaluable to researchers who are interested in the emerging areas of the field. Graduate students in related areas as well as lecturers will also find it beneficial. Some of the chapters have been written by distinguished experts in the field. Sample Chapter(s). Chapter 1: Detecting Mosaic Structures in DNA Sequence Alignments. A private academic research institute that supports research in physics, mathematics and the theoretical sciences. Mathematical Biosciences publishes work providing new concepts or new understanding of biological systems using mathematical models, or methodological articles likely to find application to multiple biological systems. Papers are expected to present a major research finding of broad significance for the biological sciences, or mathematical biology. Mathematical Biosciences welcomes original.

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How can an organism grow to form a desired structure and pattern? Understanding the morphogenesis of an organism, the collective self-organization of cells that gives rise to a functional structure is at the heart of decoding life. We aim to identify the rules of development by studying the physical principles underlying the formation and adaptation of biological organisms. Currently we investigate the mechanics of plant growth and the fluid dynamics enabling the slime mold Physarum polycephalum to adapt its network-like body to its environment. Our approach is combining both theoretical physics and experiments. On the theoretical side, we use analytical and numerical methods from mechanics, fluid dynamics, statistical physics and non-linear dynamics. On the experimental side, we investigate the adaptation dynamics of Physarum polycephalum with bright-field microscopy, transformations, micro-injection and tailored quantitative analysis. As a recent addition to our experimental side we investigate animal vasculature formation and adaptation in vitro and follow the flow and transport dynamics of porous media.

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For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome Take a look at our BETA site and see what we’ve done so far. Search and browse selected products Purchase these through your usual distributor The analysis of small molecules in biological samples is frequently hindered by the presence of protein and various enzyme activities. Many bioassays require removal of protein from samples prior to analysis. Perchloric acid (PCA) precipitation is one of the most extensively used deproteinization protocols since it not only removes most of the protein present in the sample but it also functions to stabilize many of the small molecule analytes. PCA deproteinization has been successfully used in the preparation of samples prior to quantitation of an array of small molecules, including glycogen, ATP, cAMP, glutathione, antioxidants, etc. Samples are now deproteinized, neutralized and PCA has been removed. The samples may now be used directly for the relevant assays.

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The lasso peptide Benenodin-1. Credit: RCSB The 2016 Nobel Prize in Chemistry honored three esteemed scientists in the field nanotechnology for their contribution of synthetic molecular machines. Molecular machines, the assemblies of molecular components that produce mechanical movements in response to specific stimuli, are common in nature. The most complex molecular machines are proteins found within cells. These include motor proteins, such as myosin, kinesin, dynein, and transmembrane ATPases. The structure and working mechanism of these proteins are far more sophisticated than any artificial molecular machine so far. While exploring the DNAs of a soil proteobacterium known as Asticcacaulis benevestitus, a team of Princeton University researchers stumbled upon a lasso-shaped bacterium-derive peptide that alters its configuration when exposed to heat. It belongs to a family of peptides called the “lasso peptides”. They all have an N-terminal macrolactam macrocycle ring, through which a linear C-terminal tail is threaded. This unique threaded-loop structure earned them their name. Thermal unthreading of the Lasso Peptides Astexin-2 and Astexin-3. Credit: Allen et al., 2016/ACS Chemical Biology Most lasso peptides undergo a conformational change when exposed to heat, eventually resulting in the tail slipping out of the ring and the peptide losing the “lasso” feature. But what is unique about benenodin-1, the peptide isolated from A. benevestitus, is that even though the peptide changed configuration, it never becomes unthreaded. The team, led by A. James Link associate professor of chemical and biological engineering at Princeton, has long been searching for inspiration from nature to construct nanoscale molecular machines. Instead of using the purely synthetic components, they went after naturally existing peptides and proteins. "The discovery of this lasso peptide, which we named benenodin-1, demonstrates that we might look to biology as well as engineering for source material in developing molecular devices," said Link. The structure of a rotaxane molecule. Credit: Wikipedia Commenting on the uniqueness of benenodin-1 as a lasso peptide, Link admitted that the ability to change shape without unthreading is intriguing. Since both conformations, before and after heat exposure, maintain the rotaxane structure, it is the first example of switchable, mechanically interlocked molecule found in nature. (Rotaxane, a mechanically interlocked molecule with ring-and-rod architecture, is an early generation molecular machine developed by Nobel Laureate Sir J. Fraser Stoddart's. Held together by its mechanical bonds, the lasso peptides are structurally resembling rotaxanes.) About the direction of the next step research, the Princeton team is attempting to put the switching property of benenodin-1 to test in practical applications, such as binding metal pollutants to help with environmental cleanup.

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Behavioral Health Drug Updates This year the Federal Drug Administration’s Center for Drug Evaluation and Research (CDER) approved a number of new drug therapies to treat behavioral health conditions, including new drugs for treating attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and more. What do behavioral health care providers need to know about these new medications? Genoa Healthcare’s Vice President of Pharmacy Solutions Abbie Vogler, PharmD, recently hosted a webinar in which she addressed new behavioral drugs and their unique attributes. To learn more, watch the webinar, which: - Explores new behavioral health drugs approved in 2021 - Reviews 2020 drug approvals and the recent pace of FDA approvals - Looks ahead to coming drug trends - Provides an update on COVID-19 vaccine developments To learn more about how Genoa can help you and those you serve, contact us today.

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Passionate, experienced, Osteopaths committed and focused on helping you to find health and thrive. Established in 2007, Dale Wilson began the clinic with a focus on an extensive training in a Biodynamic approach to cranial Osteopathy. Our treatment is tailored for the whole family, especially infants, children, and pregnancy. FINDING HEALTH OSTEOPATHY GEELONG & SKENES CREEK Osteopathy is a system of diagnosis and treatment for the whole patient. Osteopaths use their hands for the manual treatment the whole body, The whole is the sum of the parts, This includes the bones, muscles, nerves, lymphatics, and circulatory systems, The treatment is aimed at restoring the normal relationship between structure and function, to support normal physiology and subsequent health. With the use of our hands, Osteopaths attempt to restore balance throughout the whole organism, and in doing so promote homeostasis. We attempt to get to the diagnosis by listening to the tissues and the movement of the body, and from this diagnosis we can come up with a treatment plan that will work for you. We always work towards finding and treating the cause, in order to re-establish a place where the whole can come to balance. Our primary role as health practitioners is to find Health, not disease. The health in the system is where the power comes through to create the change necessary for healing, and normal growth and development. We treat you as a person, not a number. Our approach is always individualistic, and never templated. Starting with the whole person is how we are able to get the best results. Our initial consultation is about how we begin to understand you, and ultimately find your health. Our diagnostics begin with listening. We listen to your story, and begin to develop a picture of your overall health. This picture is important, as it represents you and your life journey. It also allows us to further hone in on problem areas, or any red flags that show up. We move from listening to asking any relevant questions. This is an Osteopathic case history, as such. Questions are still very individualised, and specific to whatever has showed up thus far in the initial conversation. These will help lead us further into knowing where to start with the treatment. We may then ask you some further questions around your general health and wellbeing, and a more complete history that covers all the aspects of your state of health, both past and present. We will also ask you your goals with treatment, and what you would like to get out of the consultation. Osteopathic treatment varies significantly, depending on the presentation, and the preference for treatment modalities from the patient and the practitioner. If you have a treatment preference, based on past experience or just a personal preference, please let us know. We will be happy to do what we can to accommodate your needs. If the practitioner you’re seeing any issues, they will chat with you so you can work out a solution together. We are here to help you. Check your Insurance Extras For Osteopathy. Dr Dale Wilson DIRECTOR - OSTEOPATH Dale has been working and studying Osteopathic medicine for over 20 years. Throughout this time, Osteopathy and its deeper truths have been a central focus in his life and in his service to the community. Like many people, Dale didn’t know what Osteopathy entailed until he received a treatment. This experience had a huge influence on his whole being, igniting a passion for Osteopathy as a form of healing and service that has burned brightly throughout his career. Since completing his formal studies at RMIT in 2004, Dale’s post graduate study has focused on a Biodynamic approach to Osteopathy in the Cranial Field, a specific approach to Osteopathy. This approach to manual medicine has shown Dale what is possible when the practitioner is truly neutral and free to “listen” with their hands, aligning with the intention of the healing process that is already present in the patient. This approach can work well with many conditions, both acute and chronic, and is particularly helpful in the treatment of pregnancy, infants and children. Dale enjoys treating a vast array of presentations, and loves the opportunity to see people in a family focused orientation. In his downtime, Dale likes to relax in the garden and the forest where he lives with his wife and his dogs, swimming together in the ocean, and enjoying time to contemplate nature and awareness. Dr Beth Clarke Beth deeply values the gentle nature of Biodynamic Osteopathy, and recognises its application to all ages and stages of life, particularly pregnancy and infancy. Beth especially enjoys working with babies and children, with whom she has a natural affinity, viewing the world with a sense of wonder, fun and discovery. Beth is proficient in treating birthing trauma, which many infants have experienced, and other childhood disorders. The biodynamic approach is equally suited to treating the elderly, with whom Beth has a deep connection, respect and understanding. Dr Jamie Parker LONG TIDE OSTEOPATHIC RETREAT SKENES CREEK, OTWAY NATIONAL PARK Long Tide retreat is a wonderful healing space that both Dale and Jackie run as a guest house in Skenes Creek. The guest house is situated 5 minutes back off the great ocean road, high in the hills amongst the tall trees in the Otway National Park. The location is magical, the views are stunning, and the retreat space is so relaxing. The guest house as an adjunct to Osteopathic care, has been a vision of Dale’s for many years. It is his hope and his wish that this space will allow people to come and get treated, and access deep rest. Dale believes this combination allows the individual the best opportunity to heal, and to get the most out of the dynamic exchange that occurs during a treatment. Along with being supplied with some fresh seasonal organic food from the self-sufficient garden, the guest/s will be free to take walks through the 170-acre property. Soaks in the magical rain water fed bath, warmth from the wood fire, and rest in the comfortable king bed. It’s an opportunity to look after you.

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Johns Hopkins computational biologist recognized for his contributions to the first complete sequencing of the human genome ©By Jill Rosen TIME today named Michael Schatz, a computational biologist and one of the world's leading genomics experts, to its 2022 list of the 100 most influential people for his contributions to the first complete sequencing of the human genome, "the most complete look yet at the genetic script underlying the very nature of who we are as human beings." A Bloomberg Distinguished Professor of computer science and biology at Johns Hopkins University, Schatz harnesses the power of computing to better understand human and agricultural genetics. His ongoing work to demystify the structure and function of genomes is leading directly to deeper knowledge of human diseases, targeted medical treatments and improved plants and crops. Schatz shares TIME's honor with Telomere-to-Telomere Consortium colleagues Adam Phillippy, Karen Miga and Evan Eichler. "Dr. Schatz embodies the highest aspirations of universities like Johns Hopkins and the impact they can make on the world," said Johns Hopkins University President Ron Daniels. "He has pushed the boundaries of computational biology to decode successfully one of the greatest mysteries of our species. This extraordinary feat of international interdisciplinary research will fuel scientific and medical advancements for decades to come." Twenty years ago, Schatz was working in cybersecurity when he abruptly changed his career trajectory to genomics, inspired by breakthroughs coming from the Human Genome Project, the first attempt to decipher the human genome. Being integral to the ultimate completion of that project has been a dreamy affirmation of both that choice and what has become his life's work, being a pioneer in the "genomics revolution." "The telomere-to-telomere project has been a capstone result for my 20-year endeavor to improve and complete the human genome," Schatz said. "Moving forward, I'm excited to consider how we will be able to use this new genome and the genomic technologies we developed to build it to improve so many aspects of society, from agriculture to health care, and especially our understanding of cancer. "I also feel enormous gratitude to all my students, postdocs, lab members, colleagues and mentors that helped me to reach this recognition. I feel like I am accepting this award on behalf of all of them as much as for myself. And finally, I see this as a call to give back to the community to help support those that historically have not been able to participate in the genomics revolution." As a Bloomberg Distinguished Professor, Schatz has appointments in both the Whiting School of Engineering and the Krieger School of Arts and Sciences, where divisional leadership was thrilled to learn about the TIME 100 honor. "Mike is a dedicated and visionary researcher, whose discoveries will have a profound impact on basic research and on clinical practice," said Whiting Dean T.E. "Ed" Schlesinger. "Our ability to understand and quantify an individual's genome represents a major breakthrough, both in terms of understanding DNA's role in disease risk and in realizing the promise of personalized medicine. This is a well-deserved honor for Mike and his colleagues and I have no doubt that his achievements will benefit generations to come." "DR. SCHATZ EMBODIES THE HIGHEST ASPIRATIONS OF UNIVERSITIES LIKE JOHNS HOPKINS AND THE IMPACT THEY CAN MAKE ON THE WORLD." _ Ron Daniels President, Johns Hopkins University Added Krieger Dean Christopher S. Celenza: "This is well-deserved recognition for one of our remarkable scientists. His extraordinary work with the team assembling the first complete sequence of a human genome is profound. I know his research will create opportunities for new, life-changing discoveries." Schatz joined Johns Hopkins in 2016, coming from Cold Spring Harbor Laboratory on Long Island in New York, where he was an associate professor in the Simons Center for Quantitative Biology, served as the co-director of the Undergraduate Research Program, and co-led the Cancer Genetics & Genomics Program in the CSHL Cancer Center. Earlier this year it was announced that a team Schatz co-led had created a cloud-based platform that grants researchers easy access to one of the world's largest genomics databases. Known as AnVIL (Genomic Data Science Analysis, Visualization, and Informatics Lab-space), the new platform gives any researcher with an Internet connection access to thousands of analysis tools, patient records, and more than 600,000 genomes. Vice Provost for Research Denis Wirtz said that type of collaborative spirit is typical of Schatz, whom he calls a "scientific tour de force." "In addition to being a remarkable scientist, Mike is also a tremendous colleague and collaborator," Wirtz said. "This is an incredible recognition of the type of team science that is defining the future of research." Lauren Gardner, a civil and systems engineering professor in the Whiting School of Engineering, made TIME's list in 2020 for her work developing the university's COVID-19 dashboard, which became the Coronavirus Resource Center. Posted in University News

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Clinical Pharmacy and Pharmacoepidemiology (IPSUM) Our research focus is to promote correct use of medicines at individual and societal level. By combining clinical pharmacy practice and pharmacoepidemiology research, we focus on Identification and Prevention of SUboptimal use of Medicines on patient- and societal level. In addition, we explore patterns of medicine use associated to age and gender in patients and prescribers. Furthermore, we study possible beneficial outcomes from interdisciplinary collaboration between pharmacists and other health care professionals. Our resent projects has documented: - Suboptimal patient outcomes after non-compliance to hospital guidelines on antibacterial therapy - Improper prescribing to the elderly - A large proportion of patients with coronary artery disease do not achieve the therapeutic goals - Up to 80% of drug lists in hospitals are incorrect - High prevalence of drug-related problems - Low quality of information of medicine use after hospital discharge - Unnecessary use of dietary supplements - Hormonal contraceptive use and association to nose carriage of Staphylococcus aureus - Low dose naltrexone and concomitant use of other medicines

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Older adults in the U.S. take more prescription medications than any other age group: According to a report by the Centers for Disease Control and Prevention, about one-third of adults in their 60s and 70s use five or more prescription drugs. (The most commonly used drugs are prescribed for cholesterol, high blood pressure, and diabetes medications.) “With multiple medication use, patients are at an increased risk of adverse effects,” said Dani Markus, a pharmacist who leads product development and clinical initiatives to optimize medication use at Cardinal Health Outcomes™. The Outcomes™ Personal Pharmacist Network provides medication therapy management (MTM) services – including conducting medication reviews, ensuring patient adherence, addressing gaps in therapy, referring patients to other care providers and more – to patients nationwide. “Medication-related problems include inappropriate dosing; negative interactions between various prescriptions, or between prescriptions and over-the-counter medications; drug-disease interactions (when a medication prescribed to treat one condition worsens another condition or even causes a new one); gaps in medications; medication non-adherence (not taking medications as prescribed); or taking medications that are no longer needed.” Any of these problems can cause a wide range of side effects, including falls, cognitive decline, increased hospital admissions and increased use of emergency departments. The more prescriptions and supplements a person takes, the higher the risk of side effects, Markus said. The benefit of a comprehensive medication review (CMR) With a CMR, pharmacists use their medication expertise to review all of a patient’s medications, looking for any potential problems. As defined by the National MTM Advisory Board, “a CMR is a systematic process of collecting patient-specific information, assessing medication therapies to identify medication-related problems, developing a prioritized list of medication-related problems, and creating a plan to resolve them with the patient’s caregiver and/or prescriber. A CMR is an interactive person-to-person consultation conducted between the patient and/or caregiver and the pharmacist and is designed to improve patients’ knowledge of their prescription, over-the-counter (OTC) medications, herbal therapies and dietary supplements, identify and address problems or concerns that patients may have, and empower patients to self-manage their medications and their health condition(s).” During the conversation – which typically takes approximately 30 minutes – the pharmacist asks questions to learn whether the patient faces any challenges in taking medications as prescribed. These might include financial or transportation barriers that make it hard to get prescriptions filled or refilled, lack of care coordination among providers, or a lack of understanding about what a medication is for. “The CMR provides a great opportunity to educate the patient about each prescription, how it works, and why it’s necessary – or why it isn’t necessary,” Markus said. At the end of the conversation, the pharmacist develops a comprehensive medication list and a customized action plan to provide to the patient and the patient’s other health care providers. CMRs have been shown to increase patient engagement by empowering patients in their own care: These comprehensive reviews with pharmacists help patients manage their chronic conditions better, reduce hospital admissions and emergency department visits, and reduce costs. CMRs are considered so important that the Centers for Medicare & Medicaid Services (CMS) requires health plans to provide an annual CMR to all members who are covered by Medicare Part D and meet specific eligibility criteria, including having multiple chronic conditions, taking multiple prescriptions, and meeting an annual medication cost threshold. Partnering with Community Health Group to provide quality CMRs For several years, Outcomes™ has leveraged its scalable technology and expansive network of pharmacies to deliver a variety of MTM services to the patient members of Community Health Group (CHG), a nonprofit group health plan in San Diego County, California. CHG serves more than 320,000 members, including many older adults and a significant number of Spanish-, Vietnamese-, and Arabic-speaking patients. In 2019, CHG and Outcomes™ wanted to measure just how much impact CMRs have. Ross Frei, Outcomes™ senior product manager, explained, “Both our organizations believe in the core value of the CMR – we’ve seen how CMRs can improve the health and quality of life for patients. But CMS reporting requirements only ask for a “yes” or “no” response to the question of whether the patient received a CMR. That simply doesn’t lead to solid evidence about the real value of a CMR. We wanted to be able to quantify the results.” Ashley Teijelo, CHG’s former pharmacy director, said, “We started with a shared vision: We want to provide CMRs to empower patients to better manage their medications and their health conditions. And we want to understand the expected return on investment for a pharmacist-led program based on the health care costs of members who received a CMR versus those who did not. We knew when we began this analysis that we wanted to expand our CMR program to reach more patients, and we needed a better understanding of the cost, the impact, and the savings.” The Outcomes™ team provided in-depth training to the small pharmacy staff at CHG; then, over the course of 2019, the Outcomes™ Personal Pharmacist Network and the CHG pharmacists conducted one-on-one CMRs with about 1,000 patients through the Connect™ Platform, a digital solution that provides easy access to patient-specific information to resolve medication problems, deliver clinical services and educate on key health care topics. For the 2019 benefit year, they targeted patients who met certain criteria: Analyzing the results At the end of the benefit year, the team studied the records of all patients who were enrolled in CHG for all 12 months and who met the CMR criteria above, then compared total health care costs, pharmacy costs, and medical costs. CHG members who received a CMR averaged a 5% lower total cost of care compared to the members who did not. They also spent less time in the hospital, decreased their overall cost of care, and had improved health outcomes. They repeated the process in 2020, and again studied the patient records at the end of the year. This analysis showed even more savings: Those who had a CMR averaged a nearly 17% lower total cost of care. In 2020, CHG members who received a CMR also realized: “We can’t be sure that all of the savings are the result of CMRs,” Teijelo said. “Those members who were more willing to participate in CMRs may be more engaged with their providers generally, and more likely to ask questions about their medications – and therefore more likely to have better health outcomes even without the CMR. In addition, 2020 was a highly-unusual year; hospitals were overwhelmed with COVID-19 patients, and the COVID-19 pandemic made it more difficult, if not impossible, for patients with non-COVID conditions to visit physician offices or emergency departments. “However, anecdotally I can say that as the Outcomes™ pharmacists and our staff pharmacists conducted CMRs, we often heard comments from our members, like, ‘Wow. No one ever told me that,’ about various medications they were on, how the medications impact the body, and how they interact with each other. Those ‘aha!’ moments are really meaningful for patients.” Frei said, “In this analysis, the CMR did increase the cost of pharmacy services and specialty services, but even when these are factored in, the reduction in health care costs is very significant.” Added Markus, “We were pleased to see the positive impacts of the CMRs. Better health for less cost is what we all want. The success of this partnership points to the powerful role pharmacists can play in improving patients’ health.”

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- Cancer Information - Family and friends - Talking to kids about cancer - Talking: When cancer won’t go away - How children react How children react How you react to a diagnosis of advanced cancer can affect how the whole family responds. If you are anxious and depressed, the family may be too. Some studies of people with advanced cancer show that family members often feel more distressed than the person with cancer. This seems to be more common if family members don’t communicate well. When children find out that the cancer is advanced, they may have similar but more intense reactions than when they found out about the original diagnosis. They are likely to feel insecure, although teenagers may not want you to see this. Depending on their age, kids usually have different immediate concerns when they hear the news. See Different views of death for typical reactions from children and young people. Children of separated or divorced parents need to be given the opportunity to see their ill parent, to prepare for the loss, and to say goodbye. We thank the reviewers of this book: Professor Kate White, Chair of Nursing, The University of Sydney, NSW; Sarah Ellis, Psychologist, Behavioural Sciences Unit, Kids with Cancer Foundation, Sydney Children’s Hospital, NSW; Kate Fernandez, 13 11 20 Consultant, Cancer Council SA; Chandra Franken, Program Manager – NSW & ACT, Starlight Children’s Foundation, NSW; John Friedsam, General Manager of Divisions, CanTeen, NSW; Keely Gordon-King, Cancer Counselling Psychologist, Cancer Council Queensland; Stephanie Konings, Research Officer, CanTeen, NSW; Sally and Rosie Morgan, Consumers; Dr Pandora Patterson, General Manager, Research and Youth Cancer Services, Canteen, and Adjunct Associate Professor, Cancer Nursing Research Unit, The University of Sydney, NSW and Visiting Professor, Faculty of Health and Life Sciences, Coventry University, UK; Suzanne Rumi, Consumer; Michael Sieders, Primary School Program Manager, Camp Quality. We would also like to thank the health professionals, consumers, organisations and editorial teams who have worked on previous editions of this title, and we are grateful to the parents and young people whose real-life stories have added to the richness and relevance of this book. We thank and acknowledge Dr Paula K. Rauch, MD, Founding Director, Marjorie E. Korff PACT (Parenting At a Challenging Time) Program and Associate Professor of Psychiatry, Harvard Medical School, whose research and writing on helping parents talk to their children about cancer was used as source material for this book and has been adapted in several sections: pages 8 -11, Different views of cancer; page 24, Answering key questions: Are you going to die?; pages 26 -27, Involving the school or preschool; pages 30 -31, Prepare for hospital and treatment centre visits; and page 37, Encouraging family time. We also thank the American Cancer Society for permission to use and adapt material on pages 8 -11 from its book Cancer in Our Family: Helping children cope with a parent’s illness (2013); Macmillan Cancer Support for permission to use its book Talking to Children and Teenagers When an Adult Has Cancer (2013) as a source of information; Jessica Watt, Oncology Social Worker, Children’s Hospital Westmead, for her contribution on page 18, When another child has cancer; Diane McGeachy, Hobart Counselling Centre, for contributing material for page 38, Spending one-on-one time; and Dr Ranjana Srivastava, and The Guardian for permission to adapt €œHow do you tell your children you have cancer? €_x009d_, on pages 21 and 47 – full story is available at https://www.theguardian.com/society/2015/nov/29/how-do-you-tell-your-children-you-have-cancer. View the Cancer Council NSW editorial policy.

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A handful of scientists around the United States are trying to do something that some people find disturbing: make embryos that are part human, part animal. The researchers hope these embryos, known as chimeras, could eventually help save the lives of people with a wide range of diseases. One way would be to use chimera embryos to create better animal models to study how human diseases happen and how they progress. Perhaps the boldest hope is to create farm animals that have human organs that could be transplanted into terminally ill patients. But some scientists and bioethicists worry the creation of these interspecies embryos crosses the line. “You’re getting into unsettling ground that I think is damaging to our sense of humanity,” says Stuart Newman, a professor of cell biology and anatomy at the New York Medical College. The experiments are so sensitive that the National Institutes of Health has imposed a moratorium on funding them while officials explore the ethical issues they raise. Nevertheless, a small number of researchers are pursuing the work with private funding. They hope the results will persuade the NIH to lift the moratorium. “We’re not trying to make a chimera just because we want to see some kind of monstrous creature,” says Pablo Ross, a reproductive biologist at the University of California, Davis. “We’re doing this for a biomedical purpose.” “One of the concerns that a lot of people have is that there’s something sacrosanct about what it means to be human expressed in our DNA,” says Jason Robert, a bioethicist at Arizona State University. “And that by inserting that into other animals and giving those other animals potentially some of the capacities of humans that this could be a kind of violation--a kind of, maybe, even a playing God.”

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Post-poliomyelitis foot deformity remains a challenging problem to orthopedic surgeons, though its incidence has decreased greatly. The purpose of this retrospective study was to evaluate the surgical outcome in patients with paralytic foot deformity associated with poliomyelitis. Between 1998 and 2002, seven patients with a history of prolonged, severe, and rigid equinocavovarus deformity secondary to poliomyelitis underwent one-stage deformity correction and pantalar arthrodesis. Their average age at the time of surgery was 54 years and the average follow-up was 22 months. Fixation with multiple cannulated screws, bone staples, or K-wires was used in all patients. After surgery, no vascular insufficiency or skin sloughing developed. At the latest follow-up, solid arthrodesis was achieved in all patients and none of the deformities recurred. Painless plantigrade feet were achieved in all patients but one. Leg length discrepancy averaged 2.7 cm (range, 2-4.5 cm), which was managed with shoe lifts. In conclusion, with stringent preoperative evaluation, meticulous surgical technique, and highly compliant postoperative cast protection, one-stage deformity correction and pantalar arthrodesis can be successfully accomplished in patients with severe, rigid equinocavovarus deformity secondary to poliomyelitis. |Translated title of the contribution||以一階段Pantalar Arthrodesis治療因小兒麻痺導致之足踝關節變形| |Number of pages||7| |Journal||Journal of Orthopedic Surgery Taiwan| |Publication status||Published - Mar 1 2005| - Pantalar arthrodesis

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The complex interaction between the bones, ligaments, muscles and nerves within the foot determine its anatomy. Everything that disrupts these structures can cause flatfoot. A foot examination begins with a general examination of the whole body because flatfoot could have a hidden cause. Some of the more frequent causes of flatfoot are cerebral palsy, various forms of muscle dystrophy, early onset arthritis, genetic disorders which affect the nervous system, innate connective tissue issues. Flatfoot may be caused by an irregular anatomy such as a tarsal coalition (abnormal connection between bones), damage to the ligaments or muscles, limited ankle movement, outwardly rotated lower legs or inward tilted knees. Excessive weight may also lead to collapse of the foot arches due to the increased load. If the knees begin to tilt inwards, the foot arches may turn outwards. The foot will begin pointing outwards when walking, instead of straight, which may cause fatigue.

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Many Bunion Problems Can Be Managed Without Surgery The first line of defense to treating your bunion problems is usually more conservative in nature. We know that bunion problems are nearly nonexistent in populations that don’t wear shoes and 90 percent of those who suffer bunion problems are also women. Other areas that are important for the evaluation of the bunion problems are past medical history and family medical history. Some bunion problems can be managed without surgery and bunions that are not painful do not need surgical correction. At the big-toe joint (where the bunion problems are), both bones and forming this joint are coated using fibrous and studying the patterns in your gait can be very revelatory where bunion problems are concerned. Many people with bunion problems can be managed with the use of appropriate footwear and in some cases with the use of orthotics. Continue reading “Treat Bunion Problems Early To Avoid Surgery”

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Plantar Fasciitis: Treatment Pearls by Douglas Richie, Jr. D.P.M., President Elect AAPSM (2003 - 2004) Epidemic Of Heel Pain: Heel pain is the most common musculoskeletal complaint of patients presenting to podiatric practitioners throughout the country. It is well-recognized that subcalcaneal pain syndrome, commonly attributed to plantar fascitis, is a disease entity that is increasing in its incidence, owing partly to the fact that it has a predilection for people between the age of 40 and 60, the largest age segment in our population. The orthopedic and podiatric literature have been filled with original scientific investigations and anecdotal reports about the appropriate surgical and non-surgical approach to plantar fascitis. The vast majority of these scientific articles deal with the general patient population presenting with heel pain. There is a growing consensus of opinion that plantar fascitis is best treated non-surgically with the vast majority of patients becoming asymptomatic within twelve months of the onset of symptoms. While patience, rest and tolerance of pain are virtues recommended to the patient presenting with plantar fascitis, different treatment strategies must be employed when dealing with the athlete.This article will focus on the differences in treating plantar fascitis in athletes vs. the general, sedentary population. Subcalcaneal pain syndrome in athletes is thought to be brought on by an overload of the plantar fascia.However, the mechanism of this overload is debated.Overload causes micro-tears at the fascia-bone interface of the calcaneus or within the substance of the plantar fascia alone.The central band of the plantar fascia is primarily affected where a hypercellular, inflammatory response occurs within the fibers of the fascia, leading to degenerative changes. A spur may result from further inflammation but is not implicated as the primary source of heel pain.Many studies have shown the presence of spurs on the heels of asymptomatic patients.One study found that only 10% of all calcaneal spurs visible on x-ray were actually symptomatic. Other authors have attributed "painful heel syndrome" to an entrapment of either the medial calcaneal nerve or the first branch of the lateral plantar nerve.However, the mechanism of entrapment proposed by these authors is still related to overload of the soft tissue and fascial structures on the plantar and medial aspect of the calcaneus. Although heel pain is common, there is no commonality of opinion of the biomechanical etiology of this syndrome.Contributing factors reported in the literature include leg length inequality, pronation of the subtalar joint, restricted ankle joint dorsiflexion, weakness of plantar flexion, high arched feet, low arched feet and heel strike shock.Studies have shown that decreased arch height has shown no correlation to the development of plantar fascitis in runners.In fact, it is well accepted that the common athlete presenting with heel pain has a medium to high-arched foot. Scherer and coworkers have given the best insight into the pathomechanics of plantar fascitis.Their study proposed that supination around the longitudinal axis of the midtarsal joint is a common feature in over 100 feet presenting with heel pain.Supination about the longitudinal axis of the midtarsal joint can occur in two primary situations:when the heel everts past perpendicular (heel valgus) or when a forefoot valgus deformity is present (sometimes accompanied by rearfoot varus). TREATMENT STRATEGIES FOR THE ATHLETE In most cases, the goal of the athlete is to quickly return to activities to minimize loss of fitness and performance.This will put pressure on the treating practitioner to be more aggressive than treating cases of more sedentary patients. A survey was conducted by this author of the board members of the American Academy of Podiatric Sports Medicine two years ago to compare treatment protocols for athletes vs. standard population.The following treatment pearls were elicited: 1) Assignment to alternative activity The athlete must be encouraged to maintain cardiovascular fitness during rest from damaging activities that may delay healing.For the runner, dancer or volleyball player, this means a complete cessation from running and jumping activities until acute symptoms subside.On the other hand, the athlete should be assigned to alternative cardiovascular fitness activities that minimize impact and loading on the plantar fascia including stationary cycling, swimming, upper body weight machines, and low resistance flat-footed stair master machines. 2) Change and modulation of footwear Footwear analysis is critical for evaluating athletes with subcalcaneal pain.The footwear may be a contributory factor and can be utilized as a powerful treatment modality.Athletesshould be placed into shoes that have a minimal 1" heel height with a strong stable midfoot shank and relative uninhibited forefoot flexibility.The American Academy of Podiatric Sports Medicine has a list of recommended footwear for the athlete that can be obtained on their web site:www.aapsm.org.It is well recognized that recent trends in athletic footwear have actually predisposed to greater frequency of plantar fascitis due to the fact that athletic shoes have weaker midsoles with newer designs.The popular "two-piece" outsoles with an exposed midsole cause a hinge effect across the midfoot placing excessive strain on the plantar fascia in the running and jumping athlete.These shoes must be eliminated if the injured athlete is wearing them.Careful attention must be paid to having the athlete keep shoes on in the house and during all standing and walking activities.Barefoot and sandal-wearing activities are prohibited. 3) Home therapy Athletes are accustomed to designing and participating in their own training programs.They are willing participants in their own treatment programs. Heel cord stretching is central to the rehabilitation process to decrease load on the plantar fascia and encourage healing.The use of plantar fascia night splints has been well proven to be a treatment adjunct for plantar fascitis by placing the heel cord and the plantar fascia on a sustained static stretch during sleeping hours while preventing the normal contractures that occur in the relaxed foot position during sleep.Having the athlete roll or massage their foot on a golf ball or tennis ball is helpful to improve blood flow and break down adhesions in the injury site. 4) Custom foot orthoses Intervention with semi-rigid custom foot orthoses has been well proven in many prospective and retrospective studies showing successful outcomes in patients with plantar fascitis.In the athlete, the use of foot orthoses should be considered earlier than in the average sedentary patient because of the fact that the athlete will be subjecting their feet to greater stresses during treatment and certainly after return to activity.Athletic footwear is more amenable to semi-rigid and rigid orthotic therapy than are casual shoes worn by sedentary patients.Sports podiatrists are more likely to employ arch taping procedures as a precursor to or adjunct to orthotic therapy.Athletes respond very favorably to the immediate intervention and relief obtained by expertly applied arch taping procedures. 5) Physical therapy Athletes are amenable to referral for physical therapy because they are willing to invest the extra time to expedite recovery.Many athletes are used to going to the training room for hands on rehabilitation.Athletes appreciate a partnership between the sports podiatrist and the physical rehabilitation specialist. 6) Anti-inflammatory medication Sports podiatrists should be cautioned against over-aggressive use of anti-inflammatories in treating the athlete.While it is tempting to utilize corticosteroid injections to expedite healing, athletes are often skeptical of receiving this treatment and are certainly at greater risk for sequela of over-ambitious use of steroid injections.There are reports in the literature of athletes undergoing spontaneous rupture of the plantar fascia after even single injections of their plantar fascia with corticosteroid.The conservative, biomechanical interventions outlined above should be implemented before considering injection therapy. Athletes presenting with plantar fascitis must be treated aggressively because they have immediate needs and long-range goals that are different than those seen in the average sedentary patient with heel pain.It is important to be aggressive and employ a variety of modalities and treatments when formulating a treatment plan for the athlete.At the same time, caution should be made about the overzealous use of quick fixes, including corticosteroid injections because of the potential deleterious effect on athlete. The cornerstone of plantar fascitis treatment for the athlete is biomechanical.Podiatric practitioners possess the greatest skill set and knowledge available in medicine today to adequately address the pathomechanics of plantar fascia overload.The use of properly casted and designed custom foot orthoses should be the cornerstone of non-surgical treatment of subcalcaneal pain in the athlete. Resistant Plantar Fasciitis Treatment Program (Initial) Contributed by Richard Bouche D.P.M. , William Olson, D.P.M., Stephen Pribut, D.P.M., Douglas Richie, Jr,. D.P.M. PHASE 1- Acute Phase: PHASE 2- Rehabilitation Phase: PHASE 3- Functional Phase: Note: this is probably the most important phase because it prepares the patient for their return to activity. Care needs to be taken at this stage not to allow the patient to overdo these exercises and stay within their limits as re-injury can easily occur. PHASE 4- Return To Activity Return to desired sport activity: gradual, systematic, "to tolerance" Initiate preventive strategies: appropriate athletic shoewear functional exercises (i.e., pilates, plyometrics) revise training program Note: Be careful in the first months return to exercise to avoid recurrence of pain. Consider shock wave therapy if there is a 6 month failure and a failure after repeated modification and remaking of orthotics.

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For many individuals, their big toe is not, in fact, their biggest toe. It isn’t uncommon for one of the lesser toes to grow longer than the big toe, but such a deformity can create problems both aesthetically and functionally. An abnormally long toe can appear unattractive and embarrassing and limit the kinds of shoes the person can wear, including stylish yet ill-fitting shoes and open-toe sandals. Additionally, a longer than usual lesser toe can lead to further deformity and deterioration of the toe including a hammertoe contracture of the toe. Most often, it is the toe closest to the big toe that is the one at issue, hanging off the edge of an open-toed shoe. Usually, the big toe is approximately equal in the length to the second and possibly third toe, followed by the shorter fourth and fifth toes to create a profile and shape known as a parabola. An elongated toe disrupts this parabola. For those with an elongated toe, the nail on that toe can become darkened and thickened from possible fungal infection or micro-trauma. The joints on the dorsum (top) of the toe typically rub and become irritated from the top of the shoe, causing unsightly corns, blisters, scarring, pain, and occasionally open wounds. At JAWSpodiatry, we frequently see patients who want to do something about a long lesser toe, whether for cosmetic reasons or otherwise. As with every foot and ankle problem we treat, we always consider non-surgical or minimally invasive treatment options for overly long toes, but the nature of the condition is such that toe-shortening surgery is often the only practical and effective solution. Cosmetic toe-shortening surgery can correct an abnormally long toe to allow for greater shoe options and a more pleasing appearance. If You’re Ready to Fix an Elongated Toe, Call the Foot and Ankle Specialists at JAWSpodiatry Today. If an elongated toe is causing you embarrassment or keeping you from wearing the kinds of shoe styles you want, you don’t need to live with it anymore. At JAWSpodiatry in Hollywood, Florida, our exceptional podiatrists and surgeons focus exclusively on treating foot and ankle problems. If we do recommend toe-shortening surgery, our experienced podiatrists will perform your procedure with the utmost care and precision, using the most advanced technology and methods. Please contact us today at (954) 922-7333 to schedule a consultation.

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Growing Pains Toe Walking Usually Not A Sign Of Autism And Other Problems Toddler toe walking was previously thought to indicate autism, cerebral palsy and muscular dystrophy, but a study finds toe walking is usually not a symptom of developmental problems in toddlers and young children. As babies and toddlers begin learning to walk, it’s common for them to place most of their weight on their toes and not much weight on their heels or other parts of the feet. But at what point should "toe walking” be a cause of concern for parents? According to a new study, it’s very rarely a condition worth worrying about and is rarely a symptom of developmental issues like autism. Previous research has indicated that while many cases of toe walking are idiopathic (meaning a cause is unknown) and most children outgrow the condition by the age of three, there’s a large possibility that it could be a sign of serious problems like cerebral palsy, muscular dystrophy or autism. However, a Swedish study that appeared in a 2012 issue of Pediatrics disproves previous theories and states that more than half of young toe walkers will outgrow the condition by age five, and most children who are toe walkers will not face any developmental or neuropsychiatric issues. "Walking is such a notable milestone, and if it is not typical, it is often a concern for parents and physicians," pediatrician Lee Beers, MD, who practices at Children's National Medical Center in Washington, D.C., told WebMD. "This study certainly makes me feel more comfortable when I see toe walking in children who are otherwise developing well." Details About The Toe Walking Study More than 1400 parents from the Blekinge County of southeast Sweden participated in the study. The parents were asked questions about their children’s gait and toe walking at the child’s routine 5.5-year checkup, with the following information resulting from the study: - About 5% of children toe walk at some time, but less than half were still toe walking by age five and half. - Most children who toe walk do so for the first one or two years before beginning to walk normally. - Children who are still toe walking by the age of five and a half tend to walk on their toes about 25% of the time. - 41% of children diagnosed with cognitive or neuropsychiatric disorders like autism display toe walking tendencies When Toe Walking Is A Symtom Of Developmental Problems The basic message that comes from the study is that in most cases, toe walking does not indicate an underlying developmental problem in your child. The majority of toddlers and young children who toe walk will begin walking normally on their own by the age of five or six. However, there are signs and symptoms that may indicate serious neuro-muscular and neuro-developmental conditions like cerebral palsy and autism. In addition to toe walking, they include: - Muscle stiffness in the legs - Extremely tight Achilles tendons - Lack of muscle coordination - A period of normal walking followed by sudden toe walking - Communication problems - Other physical abnormalities Parents who observe any of these symptoms in their child should contact a podiatrist or foot and ankle specialist. After examining the child’s gait, legs and feet, the doctor may then suggest a visit to a neuropsychiatric specialist (a doctor who specializes in disorders of the nervous system), a pediatric neurologist, or a physical therapist. Notice concerning medical entries: Articles having medical content shall serve exclusively for the purpose of general information. Such articles are not suitable for any (self-) diagnosis and treatment of individual illnesses and medical indications. In particular, they cannot substitute for the examination, advice, or treatment by a licensed physician or pharmacist. No replies to any individual questions shall be effected through the articles.

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I really had no intention of making this political, but I've been thinking of this expression a lot lately. and I just Googled it and I found out it's what Barack Obama said when Donald Trump became apparently elected president. It could have been the end of the world and it still might be but it hasn't been. 2020 also taught that only the end of the world is the end of the world. It's important that I pause here and acknowledge the fact that millions of people died and many millions of people got sick. 2020 was literally the end of the world for many people. But here we are in 2021, reading this. So my (very first world) problem is that I am not going to run the New York City Marathon this year. The good news is that I have an overuse injury. that was a joke.... in order to keep myself from tripping over my own toes I wear ankle foot Orthotics. From a distance they look like bands that go around my calves. But there's actually a carbon fiber rod that goes down into my shoe and there's a plate underneath my foot. It solves the problem of foot drop. It also means I'm running on a carbon fiber plate and losing all the padding that my Hookas come with. The little bone behind my big toe started not liking that. He complained by swelling. When it swells it feels like there's a electrical dumpster fire in my shoet hen the pain actually gets worse when I take off my shoe because my foot gets a chance to swell. I have a swollen sesamoid bone. Sesamoiditis. So back to physical therapy for strengthening exercises mostly around my toes . I also had a hole drilled in the bottom of my orthotic right underneath my sesamoid bone. I think that's the trick. So this morning I tried out my new feet. 300M regardless of what the GPS says. No pain. I might try a whole mile tomorrow

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3 Signs You Have Wide Feet Have you found yourself wondering if you’ll ever find a pair of shoes that will be truly comfortable? If this feels true to your experience, listen up! There are a few tell-tale signs to look out for when it comes to identifying whether or not you may have been buying the wrong size shoes this entire time. As odd as it seems, we can’t go on that initial feeling when trying on a pair of shoes alone. It’s important to factor in things like changes in weather, like heat that may cause your shoes to expand, or cold air that calls for socks which may tighten up the fit of your shoes. Did you know that by the end of the day, your feet are naturally larger than they were at the beginning of the day? This is from the way we use our feet throughout the day leading to slight swelling and expanding in normal scenarios. All of these factors and more can contribute to our feet feeling uncomfortable in nearly every pair of shoes we own, but none more so than having wide feet and not even realizing it! Check out our top 3 signs you have wide feet: When our feet are wider than our shoes, this causes our toes to be crammed in. Our big toe can be affected and develop a bunion, which is an inflamed, bony growth that causes the big toe to grow inwards. This is a problem that is often only treatable through surgical correction. One of the most annoying problems when it comes to our feet are blisters – these happen when our shoes are tight and repeatedly rub against our skin. It causes a blister to form as a defense mechanism to protect the irritated skin. It’s highly unlikely that you’ll actively notice when your feet are going flat. This can cause us to start feeling uncomfortable in shoes that were once comfortable. Whether it’s genetics, high-impact activities, going barefoot too often, or being obese, flat feet cause your feet to become wider. If you suspect you might have wide feet or if you have any other foot problems or issues mentioned above, don’t hesitate to visit us at Foot & Ankle Specialists of Central PA. Dr. Terry H. Clarke and Dr. Karen M. Leonard are here to help! Call us today at (717) 620-8225 to set up an appointment with us in Mechanicsburg, PA.

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“Oh, my aching ankle.” That’s a common refrain, some version of which we hear frequently at Essex Union Podiatry. Ankles are the source of some of the most common bone and joint injuries. While there are a variety of causes, and subsequently a variety of treatment solutions, it is crucial to understand two important sources of ankle pain: a sprain or a break (or fracture). How common are these injuries? More than a million people head to the emergency room every year with ankle injuries, and for 25,000 people a day, they are ankle sprains. And ankle fractures are numbered at approximately 187 annually for every 100,000 people, a number that is on the rise. Sprains and breaks can occur in a variety of ways—from stepping awkwardly off a curb or falling, and increasingly, from all levels of fitness and sports activities. Sprain Versus Break These two injuries can result in similar symptoms and can be hard for people to differentiate. It is important to understand the differences. The ankle joint is made up of bones, muscles, cartilage, ligaments and tendons. An ankle sprain occurs when the ligaments, a strong band of tissue that support and stabilize the ankle bones, are stretched or torn. This happens when the ankle is moved in awkwardly with a twist, turn or roll. A sprained ankle is an injury that occurs when you roll, twist or turn your ankle in an awkward way. This can stretch or tear the tough bands of tissue (ligaments) that help hold your ankle bones together. Lateral ligament sprain-This is the most common ankle sprain, one which causes a throbbing pain on the outside of the ankle. This sprain may also cause swelling and bruising. With a tear, you may also have a distinct feeling of the joint giving out. Medial and high ankle sprains-These are less frequent that lateral ligament sprains and usually occur if the ankle rolls outward. Pain is present on the inside of the ankle. If the foot rotates out in relation to the leg, it can cause a high ankle sprain (commonly seen in football players), characterized by pain above the ankle. Symptoms of an Ankle Sprain - Discolored skin - Inability to bear weight - Tender to the touch An ankle fracture occurs when one or more of the related bones is broken. These include the lower leg bones - Fibula—smaller bone of the lower leg, sometimes referred to as the calf bone - Talus—foot bones The injury can range from a simple, single break, to fractures of several bones at once. While you may still be able to walk on a single fracture, multiple fractures—which may also include ligament damage—may prevent you from walking, and require no weight bearing for several months to heal. People often have misconceptions about ankle fractures that can impede treatment and healing. Symptoms of an Ankle Fracture Depending on the severity of the break(s), you may experience: - Ankle deformity - Inability to bear weight - Immediate, severe pain - Tenderness to the touch If pain is severe or prolonged (beyond five to seven days), your first step should be medical care. While a mild sprain can heal with self-treatment (see R.I.C.E. below), if symptoms persist you should seek medical care. In addition, sprains can be tricky, as weakened ligaments tend to result in vulnerability to future injury or problems, such as ankle instability. A visit to a physician for ankle injury begins with the doctor taking a medical history and doing a physical exam of the injured area. Before ordering an imaging test, healthcare practitioners may use a set of diagnostic guidelines called the Ottawa Ankle Rules to determine if an X-ray is necessary. Tests for sprains or breaks may include: - X-ray stress test - CT (computed tomography) scan - MRI (magnetic resonance imaging) Doctors will usually start with an X-ray, because these types of imaging tests are particularly useful in diagnosing (or ruling out) fractures. The calcium in bone absorbs the X-rays, making bone stand out on the image. Fractures can often be seen clearly on an X-ray. If the X-ray shows no fracture or proves inconclusive, other imaging tests may be used. The primary remedy for ankle injury is the classic R.I.C.E. This stands for rest, ice, compression, elevation. In addition, over-the-counter anti-inflammatories can be used if they do not conflict with other medications you may be taking. In addition to R.I.C.E. and anti-inflammatories, a sprain may be treated by: - Keeping weight off with the use of crutches - Elastic bandages Depending on type and severity, a fracture may be treated by: - Immobilization—requiring a cast, brace, boot or stiff-soled shoe - Reduction—used to manipulate misplaced bones back into proper position - Surgery—in the case of a severe fracture(s) and/or ankle instability, surgery may be performed. This includes the use of instrumentation (pins, screws, plates) to properly position bones for healing. These implements may or may not be removed. If you experience an ankle injury, request an appointment with an Essex Union Podiatry specialist. We have decades of combined experience diagnosing the type of injury (sprain or break), and we will tailor a treatment plan for you as well as provide education on preventive measures to hopefully keep these injuries from recurring.

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What is the difference between a Chiropodist/Podiatrist and a Foot Health Practitioner? The titles Chiropodist/Podiatrist (and Chiropody/Podiatry) are protected by law and may only be used by those who have completed a BSc degree in Podiatry or grand-parented in 2005 by the HCPC (Health & Care Professions Council) which is the governing body for healthcare professionals. ALL Chiropodists/Podiatrists will display their HCPC registration number which begins with CH. A Foot Health Practitioner listed on this site has attained a standard of proficiency recognised by the Institute. All Foot Health Practitioners will appear without a CH number. Start your search…

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Our feet hold us up all day and help us get around, yet we tend to not give them the attention that they deserve! Here are some more reasons to take care of your feet and tips on how to do it. Why feet should be a top priority “Our feet are truly amazing – a network of 26 bones, 33 joints, 107 ligaments, 31 tendons and metres of nerves and blood vessels,” says Mike Wu, Foot Mechanics Podiatrist. “Nearly a quarter of all the bones in the body are in our feet. We also walk an average of 115,000 kilometres in a lifetime. So it’s very important for us to look after our feet.” Feet can take on quite a lot of stress and strain on a day-to-day basis – especially if you wear high heeled shoes or take part in high impact activities, such as aerobics or road running. Taking care of your feet and making sure you make good footwear choices can help prevent unnecessary problems such as blisters, hammer toes, bruised toes and even back pain. Finding comfortable day-to-day footwear When hunting for new shoes, make sure that they provide adequate cushioning, good support, and are the right size (both length and width) for your feet. Remember that not all footwear brands have the same sizing, so even if you think you know your size, it’s still important to double check the ones you’re trying on fit correctly. NZ footwear brand Ziera have been making women’s shoes for over 70 years, developing a collection that offers fashionable shoes endorsed by foot specialists that are both stylish and comfortable. “Ziera’s New Zealand design team comprises experts in the field. Our brand was founded by podiatrists and has strong heritage in developing orthotic friendly styles”, says Ziera Group design leader, Angela Roper. “Our stiletto, for example, pays attention to the foot’s pressure points, holding it in place with a firm-but-gentle touch. It retains a soft pitch by adding a platform front, to give height, but not pressure.” How to care for your feet Podiatrists estimate around four in 10 people will have painful foot problems at some stage in their lives, which means the likelihood that you may need to focus on your feet sometime in the future is quite high. Here are Ziera’s top tips on foot care: - Exercise regularly and always keep your feet warm. - Trim your toenails straight across. Avoid cutting corners. Use a nail file or emery board. - If you find an ingrown toenail, contact your GP. - Use quality lotion to keep your feet soft and moist, but don’t put lotion between your toes. - Wash your feet every day with mild soap and water. - Buy shoes that are comfortable without a ‘breaking in’ period. Check how your shoe fits in width, length, back, bottom of heel and sole. - Try to buy shoes made with leather upper material and that have room for your toes. For more information on Ziera shoes and to see their latest collection, visit www.zierashoes.com. Photo / FreeDigitalPhotos.net – photostock

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International VETistanbul Group Congress, Sankt-Peterburg, Russia, 7 - 09 April 2015, pp.650 Tendons are fibrous connective tissues which lead to transmission o f musclecontraction for ceto the bone fo reffective moving of limbs. The commoncalcanean tendon is for med by lateral and medial gastrocnmius, soleus and superficial digital flex or tendon. The commoncalcaneal tendon is at tachedto the tubercalcanei. Inthisstudy it was aimedtoreveal macro-anatomical, histological structure sand mechanical properties of common calcanean tendon. Achillestendon of rightandlefthindlimb of 5 adult New Zealandrabbitused in thisstudy. Results shared which was obtained from project of morphology and mechanicalproperties of tendo of rabbit. Data recorded which was obtained with dissection of commoncal canean tendon. Tissues stained with Crossman's triplestainingtechnic in ordertodetermineoverall histological structure and obtained resultse valuated semiquantatively. Macroanatomic and histological data visualized with photographs. Tensile and tearstrength tests appliedto the tendons in Autograph machine with 2 mm/min speed. Results revealed to form of several tables and graphics. Keywords:Achillestendon, Anatomy, Histology, Tensile strenght

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An ankle sprain isn’t a break, but it sure can feel like it. If you sprain your ankle, it’s important to stay off it, and then get help from the experts at North Texas Orthopaedic & Spine so you can recover as fast as possible. Use the online scheduling tool anytime or call the office nearest you to make your appointment for ankle sprain help today. North Texas Orthopaedic & Spine serves patients in Fort Worth, Duncanville, Allen, and the Dallas communities of South Hampton. An ankle sprain is an injury that happens when you put too much force on your ankle or move your ankle in an unnatural way. Most ankle sprains happen in accidents or during sports. With unusual pressure or motion on your ankle, your ligaments get stretched too far, and that causes partial or even total tears. There are three grades of ankle sprains. If you have any of these symptoms, don't push yourself. Get off your ankle as soon as possible. Sometimes, mild ankle sprains don't require treatment. A day or two of rest, ice, and elevation may be enough to restore you to 100% wellness. But, if your ankle is severely swollen, bruised, and you can't put any weight on it, you need to see your North Texas Orthopaedic & Spine doctor right away. Your treatment depends on the severity of the sprain and the effect it's having on your life. The team of doctors at North Texas Orthopaedic & Spine personalizes treatments. Your doctor may prescribe immobilization using wraps, compression bandages, or a walking cast. This can prevent you from further damaging the ligaments and allow them time to heal. If you're having pain that's not relieved with over-the-counter medication, your doctor may prescribe a stronger anti-inflammatory or pain reliever drug for short term use. Ice application at home can also be quite helpful in reducing swelling and pain. It's rare to need surgical correction for an ankle sprain, but in some cases, a torn ligament doesn't heal properly on its own. Your North Texas Orthopaedic & Spine doctor will monitor your healing and can perform a surgical repair if you need it in the future. No matter what your treatment plan looks like, it's important to return to full activity only after healing of your ankle is complete. Book your appointment online for ankle sprain help at North Texas Orthopaedic & Spine or by calling the office today.

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A bunion is bony prominence caused by mal alignment of the bones in the foot. Bunions result in pain, swelling and deformity of the foot and make it difficult to find comfortable shoes. Bunion surgery can be performed to realign the joint, correct the deformity, and relieve the pain and discomfort. Surgery is the only means of correcting a bunion. Surgery is also recommended when conservative measures fail to treat the symptoms of a bunion. There are many surgical options to treat a bunion. The common goal is to realign the bones in the foot, correct the deformity, and relieve pain and discomfort. The surgery is performed under general anesthesia, sometimes with a regional nerve block to help with pain afterwards. There are many different ways to treat bunions based on the severity of the deformity and presence of arthritsis. Sometimes a combination of techniques are used. Most commonly the below techniques are utilized. Distal Chevron Osteotomy with an Akin Osteotomy This technique is best for more moderate bunion deformities. During the procedure, the surgeon will make an incision over your big toe joint to perform the distal chevron osteotomy first. The joint capsule is opened, and the prominence is shaved down using a surgical saw. A V-shaped cut is made on your big toe and the metatarsal bone is shifted to bring your toe into a more normal anatomical position. The bunion is then shaved, and the soft tissues are realigned to correct the position. To get an even better visual alignment, often an Akin Osteotomy is necessary. Akin osteotomy corrects the sideways deviation of the tip of the big toe. In this part of the procedure, your surgeon makes a small cut in the proximal phalanx (base of the big toe) and removes a wedge of bone to straighten the big toe. The bony fragments are then stabilized using a screw or staples. First Metatarsalphalangeal Joint Arthrodesis This option is reserved for patients with significant arthritis at the big toe joint. It is fusing the big toe joint in an appropriate position that allows for normal function of the foot, but gets rid of the bunion pain. During this procedure, the surgeon will make an incision over your big toe joint. The the diseased remaining cartilage and bone is removed. Toe is brought into a good position and a plate with screws is placed to maintain it. The 2 bones will then grow together. This eliminates the pain from the bunion and arthritis very successfully, but does get rid of some motion. Functionally though, a fusion of the big toe doesn’t affect most people’s athletic activities. First Tarsametatarsal Joint Arthrodesis This procedure is an excellent option for patients with moderate to severe bunion deformities and no/minimal arthritis at the big toe joint. In this surgery the alignment is corrected through the joint closer to the ankle than the big toe joint (the 1st TMT joint). This allows the preservation of big toe joint motion and the normal TMT joint only has around 1 degree of motion which is usually not noticed. The Lapiplasty procedure is an excellent way to achieve this reliable correction. Risks and Complications of Bunion Surgery As with any surgery, bunion surgery involves certain risks and complications. They include: - recurrence of the bunion - nerve damage - unresolved pain and swelling - joint stiffness or restricted movement - Delayed healing or healing in the wrong position In rare cases, a second surgery may be necessary to correct the problems. Post-Operative Care of Bunion Surgery Patients should follow all instructions given by the surgeon following the surgery. These include: - Keep your dressings dry and leave them in place until your next outpatient appointment. - Do not place any weight on the operative leg. - Elevate the foot to minimize swelling as much as possible for the first 6 weeks. - Use crutches, walker or wheelchair to assist in getting around.

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With the aid of this non-invasive procedure, the body is able to cure itself. When you get up in the morning and go to the restroom, do you feel a sharp stabbing pain in your heel? Is the discomfort lessening as you move around? Plantar fasciitis is a possibility if this is the case. In Canada, plantar fasciitis is the most prevalent cause of heel discomfort. According to the Canadian College of Foot and Ankle Surgeons, almost two million Canadians are treated each year for this ailment. Plantar fasciitis affects around 10% of Canadians at some point in their lives. What is Plantar Fasciitis? A condition known as plantar fasciitis arises when the plantar fascia, a fan-shaped tissue on the bottom of the foot, gets irritated. It links your heel bone to your toes and helps to preserve the contour of your foot arch. A sharp stabbing pain occurs when the plantar fascia is stretched due to plantar fasciitis. This occurs as you take your first steps in the morning. Many folks disregard the discomfort since it lessens during the day. Chronic pain might develop as a result of this problem being untreated for a long time. You may also get weak, which may ultimately affect your ability to walk. What Causes Plantar Fasciitis? It’s possible that plantar fasciitis develops for no apparent cause at all at times. There are a number of possible causes for the illness. There are a number of factors that might lead to plantar fasciitis. - Obesity or being overweight is a condition - Wearing unsupportive shoes on a regular basis - A lot of jogging - High-impact activity may lead to overuse injuries. - It’s difficult to find a job that doesn’t involve a lot of walking. - Standing for lengthy periods of time on harsh surfaces - Being born with a high arch Why Is It So Hard To Get Relief? When it comes to plantar fasciitis, you may have previously tried icing the region or doing stretches. It’s hardly surprising that these therapies don’t work, given how much time you spend on your feet each day. If your profession requires a lot of walking or standing, you may not be able to rest a hurting heel since you’ll be putting a lot of stress on your feet. This might prolong the ailment. If you suffer from plantar fasciitis, these medications are unlikely to provide long-term relief. Shockwave Therapy in Langley For Plantar Fasciitis As a last resort, steroid injections, custom orthotics or invasive procedures were the only alternatives for treating plantar fasciitis that didn’t work. A rapid reduction in edoema and inflammation is achieved by injecting steroids. These, on the other hand, should not be utilized long-term due to the risk of weakening the tendon. Pain from plantar fasciitis may be alleviated with custom orthotics. A customized shoe with an insert is required in order for the orthotics to operate. It’s possible that you won’t want to wear the same pair of shoes every day. Any operation that involves cutting into your foot or ankle might have long-term implications on your health, including a weakening of your foot’s arch. In addition to a lengthy recovery period, surgery necessitates a lot of time off from work. Extracorporeal Shock Wave Therapy, or ESWT, is a novel FDA-approved therapy for this illness that is non-invasive and does not need surgery. This cutting-edge technique is less dangerous than a surgical procedure. The healing time is also quite short. Most Importantly, Non-surgical shockwave therapy in Langley for plantar fasciitis alleviates heel pain in a matter of minutes. Plantar fasciitis sufferers may now benefit from this cutting-edge and very effective treatment. ESWT is safe and effective. The FDA has given its approval based on scientific investigations that were randomized and double-blinded. 2 Plantar fasciitis patients benefit greatly from shockwave therapy in Langley, which is now the most effective treatment available. How Does It Work? Shockwave treatment helps the body cure the inflammation and damage to the plantar fascia, which is the root cause of plantar fasciitis. With the use of a specific probe, shockwave treatment delivers pressure waves into the skin. Inflamed tissue is the final destination of these waves once they pass through the skin. Natural healing processes are triggered, and new blood vessels are formed. Reduced inflammation and good cell regeneration occur as a consequence of increasing oxygen and blood flow to the region. Collagen, an important component of connective tissue, is produced as a result of this process as well. The process is simple and straightforward.

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If you’re suffering from foot or ankle pain, custom orthotics in Newtown, PA may be able to help. They can treat a wide variety of conditions involving your feet, ankles, and legs. At Newtown Foot and Ankle Specialists, our experienced doctors can assess your condition and determine if custom orthotics can ease your pain. What are Custom Orthotics? Orthotics can be a shoe or shoe insert that’s designed to alleviate pain, control certain conditions, and provide support to the foot and ankle. You can get store-bought orthotics, but those are considered one size fits all and are made for a wider audience. With custom orthotics, our team works with you to create a solution that’s suited to your particular issue. We utilize advanced 3D imaging to get a full look at the exact measurements and nuances of your foot or feet. We work with a local lab that’ll build your orthotic device to the exact specifications that were measured. What Can Custom Orthotics Help Treat? Custom orthotics can be used for a wide variety of issues. This is what makes them such an efficient tool for podiatrists. If you’re struggling with any of the following types of pain or conditions, consider contacting Newtown Foot and Ankle Specialists to see if custom orthotics are the solution for you. First, custom orthotics can help with both flat feet and high arches. Flat feet often lead to pain in your feet, ankles, and back. Orthotics can provide support to flat feet to alleviate that pain or pressure. High arches can put stress on your foot muscles. Orthotics can make sure your feet don’t roll, as well as further stability. Without treatment, high arches can lead to shin splints, plantar fasciitis, and knee pain. If you’ve injured your foot or ankle, orthotics can help prevent further injury. They keep the foot and ankle stable and provide support. They can also help with arthritis in either of these areas. Orthotics can provide stress relief for the area and absorb any pressure in those areas as well. For plantar fasciitis, they can help relieve the pain that this condition causes in your heel. If you have hammer toe, you need extra support for the ball of your foot and second toe. Orthotics can provide that and prevent hammer toe from getting even worse. Since bunions are often painful, orthotics can also be used to minimize pressure on the big toe so that bunions are easier to deal with. Lastly, orthotics can help alleviate pain in your back, legs, ankles, and feet. They can be designed to offer extra cushion for your feet, alleviating pain that can radiate to various parts of your body. This is often a concern especially if your job or lifestyle requires you to spend a lot of time on your feet throughout the day. Newtown, Pennsylvania Custom Orthotics Newtown Foot and Ankle Specialists is a facility with multiple podiatry specialists to help alleviate your foot and ankle problems. Call us today or schedule an appointment online to get started.

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The Split Second Effect The Mechanism of How Equinus Can Damage the Human Foot and Ankle James Amis, M.D. J. Amis. The split second effect: The mechanism of how equines can damage the human foot and ankle. Frontiers in Surgery, 3(38), 2016. The gastrocnemius contracture or equinus is well known to cause the majority of non-traumatic acquired foot and ankle problems. Till now the rapidly mounting evidence has only been an “association”. We know both equinus and let’s say, plantar fasciitis, most often coexist, but how are they related? In other words, how can a calf that is too tight cause all these problems? The split second effect describes in detail exactly how equinus, a calf that has become too tight, can silently and progressively damage an otherwise “normal” human foot. The split second effect describes in detail exactly how equinus, a calf that has become too tight, can silently and progressively damage an otherwise “normal” human foot. The missing mechanism described by this effect is exactly why my colleagues and people in general have considered equinus as nothing more than a random association. This association can no longer be ignored. - Where did we come from: the perfect human foot explains - What about our unique bipedal (two leg walking) gait leaves us so vulnerable to these damages unlike quadrupeds (four leg walking) - There are two critical parts to the split second effect mechanism: - the ankle dorsiflexion component - the knee extension component - And all this damage occurs with every step in just 120 milliseconds or a 10th of a second: a split second

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Relieving your feet at work Out and about all day in work boots – it won’t be long until you suffer from foot pain, especially if you have a foot misalignment: the most common foot problems include arch-decreased foot and splay foot, skew foot or mild high-arched foot. The result is often more than just painful feet and heels because the entire body structure is affected. Knee and back pain may then be additional problems. Special orthopedic foot orthoses for work safety boots provide support and alleviate pain. ErgoPad work:h+ is certified for numerous safety boots made by different manufacturers. It is also ESD-conductive, thanks to integrated carbon fibers. The foot orthosis’ tear-resistant and gripping bottom coating ensures that it remains securely in position in the shoe. The ErgoPad work:h+ is also characterized by its exceptional breathability. The synthetic core of the foot orthosis supports the foot arches and relaxes the tendons underneath the foot. A softly cushioned cut out in the heel area provides the heel with targeted relief. Tested quality provided by experts Foot orthoses for work safety shoes are only available from medical retailers. The orthotist will measure your feet and then use an orthotic blank to make a customized foot orthosis for you that will provide relief during work. Find safety footwear certified with ErgoPad work:h+ using our online shoe finder.

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Most doctors agree that walking is a great way to improve or maintain your health. This is especially important as many of us are now working from home. But what if your “gait,” or the way someone walks, is contributing to some of the aches and pains you may feel in your body. There are some ways that you can work to change or improve your gait to make walking painless. This should be prefaced by saying that everyone is different and there is no one-size-fits-all approach that will work for everyone. Some individuals may have anatomical differences that predispose them to a specific type of gait, and many people walk with slight differences with no pain at all. BUT, if you are finding yourself dealing with pain during or after walking, it may be worth it to review some common biomechanical faults in walking techniques “Overpronation” is a common term that many in the walking and running community have heard of ad nauseum. If we look down at our feet, overpronation is when the arches of our feet collapse inwards as we take a step. In severe cases, this can have a cascading effect that can lead to our knees collapsing and our hips rotating inwards. Overpronation can lead to a common type of foot pain called “Plantar Fasciitis.” The hallmark sign of Plantar Fasciitis is pain near the heel of the foot that is especially painful during those first few steps in the morning. If this sounds like something you may be suffering from, the first thing you will want to do is to take a look at your footwear. Many people suffering from Plantar Fasciitis can benefit from shoes with more arch support during their walks. Orthotic insoles are also a good option for greater arch support and have the added versatility of being able to be inserted in other shoes like your more formal shoes to improve your gait. After reviewing your footwear, it is possible that your gait could also benefit from a stretching routine. You’ll likely want to stretch out your calf muscles. Many people know how to perform the calf stretch by either going into a lunging position while keeping your heels down or propping your foot against something and leaning forwards. A pro-tip for calf stretching is to make sure to perform the stretch first with the knee straight on the back leg and then again with the knee bent. This will ensure you are stretching both calf muscles, the gastrocnemius and the soleus. These stretches should be performed gently and should be discontinued if you start experiencing pain. It is generally recommended to hold stretches for a cumulative time of one minute. Walking is still a great way to get a boost in both your physical and mental health, and hopefully these tips can help with any aches and pains that you experience in your gait. If you continue to have pain, whether in your feet or somewhere else in your body, your physician or a Physical Therapist can help find the root cause and come up with a game plan to help keep you moving. Dr. Rafael Cui, PT, DPT is a Physical Therapist at Kinetix Physical Therapy

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Tennessee Titans star player Jake Locker will be down for a while due to foot surgery he needs, but he won’t be missing out on the things he already had planned. Next Monday Locker plans to hold the Titans and T-Bone fundraiser, an event he is hosting for the first time for his new charity the Pass it On foundation. Even though he will be sidelined for the rest of the football season because of the Lisfranc injury in his foot, he refuses to lose his hopeful attitude. “I’m looking forward to getting it fixed and starting the healing process,” Locker said. “I feel confident I’ll come back stronger than I was and I’ll have no side effects from this injury.” Foot surgery is a serious proposition that should only be done after a full medical consultation. If you are thinking about surgery to fix your foot injury, visit a podiatrist like Dr. Bryant Tarr of Sudbury and Westford Podiatry. Dr. Tarr can assess your condition and walk you through all the corrective options available to you. When Is Surgery Necessary? Foot and ankle surgery is generally reserved for cases in which less invasive, conservative procedures have failed to help with the problem. Some of the cases in which surgery may be necessary are: - Removing foot deformities like bone spurs and bunions - Severe arthritis that has caused bone issues - Reconstruction to attend injuries caused by accidents or malformations What Types of Surgery Are There? The type of surgery you receive will be dependent on the nature of the problem you have. Some of the possible surgeries include: - Bunionectomy for painful bunions - Surgical fusion for realignment of bones - Nerve removal for painful nerve endings Benefits of Surgery Although surgery is usually a last resort, when it is undertaken, if can provide more complete pain relief than before, and may allow you to finally resume full activity. Surgical techniques have also become increasingly sophisticated. Such techniques like endoscopic surgery allow for smaller incisions and faster recovery times. Read more about Foot Surgery.

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One of the most common reasons people present to podiatrists is for the treatment of Flat Feet. A flat foot can be described in many ways, fallen arches, rolled in ankles, or over pronated. This type of foot is relatively common in children. Many children with flat feet remain symptom-free for many years. However, in many cases if this foot type continues through to adulthood, it may become symptomatic and can be a causative or contributing factor for many other foot problems. If in doubt have our professional staff check it out. Excessive or inappropriately timed pronation (rolling in) can result in overuse injuries and fatiguing muscles. The Flat foot type forces the muscles of the leg to work harder than if the foot had the stability of a constant arch. This may in turn lead to leg or lower limb pain. The foot requires a certain level of pronation (rolling in) to walk, function efficiently and absorb shock for the body. In addition, the foot requires an equally important amount of supination (rolling out) so that it can propel the body forward as we walk. It is normal for children to lack this ability to form an arch whilst standing, as the bones in their feet are not completely developed. Therefore they lack the normal structure of an adult foot. Kids feet don't look like adult feet! From birth to around the age of 8 years, flat feet are considered to be relatively normal. During this time a noticeable arch should begin to form. Kids often don't complain of pain or sore feet! So it pays to be alert. Take note if the child is presenting with pain, is tripping or unsteady on their feet, or if they seem to be fatiguing faster than other children. Also note if their toes are clawing onto the ground, or you notice they are overly flexible. Any one of these symptoms is generally considered reason enough to undertake a thorough assessment by one of our highly qualified podiatrists. If you have any concerns get it checked out! A note about growing pains - An increasing number of children are diagnosed with growing pains by well-meaning practitioners. Please consider having your children's feet checked. It is our opinion that many times growing pains may be able to be stopped by simply looking at how your child walks or runs and treating any imbalances. A Step Ahead Foot + Ankle Care has had extensive experience in this area and success in its treatment. Signs and symptoms for parents to watch out for: - Foot or arch pain - Tripping or falling - Muscle fatigue or soreness - Hip pain - Back pain - Clawing toes - Ankle sprains/ injury prone - Growing pains - Children not willing to participate in sport or normal activity - General fatigue What can we do for you? Resolution of pain is most often achieved through a combination of treatment modalities. Treatment may include: - A kid friendly walk/run assessment - Kid specific orthotic or insoles therapy - Footwear advice - Stretching exercises - Strengthening exercises - Deep connective tissue massage

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Therapy for your feet! You Don't Have to Suffer Anymore! There are 26 bones in your feet... did you know that's a quarter of the bones in your body!?!? Your feet have 23 joints and more than 100 muscles, tendons and ligaments. That's a lot of stuff just in your feet. It is the beginning of the kinetic chain and very commonly the cause for many problems in your knees or hips or even your neck and shoulders. For something that supports your entire body it never gets the medical attention it deserves. All those bones, joints, muscles, tendons and ligaments are under constant pressure everyday which causes them to become displaced overtime. These new positions will end up causing misalignment not only in your foot but upwards towards the rest of your body. There are countless problems that we see in clinic that are caused by long term misalignment of the feet. Here's a short list of the most common issues: So how do you fix your feet, so you don't get these issues? Or maybe you already have problems and you want to fix it? Manual therapy or foot mobilization therapy, as we like to call it, may be your answer! Foot mobilization therapy is often gentle movements the practitioner will perform on your feet in order to move your joints to realign them. The treatments are generally pain free. Treatments are 15-20 minutes and incorporates an exercise and stretching regime to help strength muscles that have become weak due to the misalignment. Everyone can benefit form realignment of your feet! Be a hero to your sidekick.

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Common Body Pain It is not normal for your feet ,legs, shoulders ,knees or back to hurt all the time. Our feet do not even have to hurt for our bodies to hurt. All they have to do is go out of aligment for your body to go out of adjustment. Footpharmacy Direct Orthotics can help you have a balanced foundation and can improve your overall health. Footpharmacy Direct Orthotics are products of years of biomechanical research resulting in an orthopedic appliance created to position all the bones, ligaments ,muscles and tendons of the human foot into their proper place and then contouring a flexible support to meet the contours.

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Beginning a different workout routine of any kind can bring to light pains or weaknesses that we otherwise would not have noticed. With yoga and hot yoga becoming increasingly popular, many people are grabbing their mats and towels and stretching parts of their body that they have never noticed they even had before! Arthritis in the big toe joint in some instances can be improved by stretching and in others it can become aggravated. People with professions that require a lot of squatting or bending the big toe joint usually already know when they start to develop arthritis because they are constantly trying to move a joint that has limited motion. In many other people, their day-to-day activities don’t require excessive motion in the big to joint. So, it is for that reason that some people start yoga and begin to notice pain in the big toe joint (and others). Yoga, by nature, is about elongating your body and involves a lot of stretching and poses. Some of these poses do require a great deal of motion in the big toe joint and if your foot type is one that predisposes you to jamming of the big toe joint, these poses and exercises will cause some pain. Typically, yoga instructors can help you modify exercises to not cause pain. If you want yoga to be part of your daily routine and your big toe is keeping you from meeting your fitness goals, contact our office today about options for treatment!

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Your feet support your body weight when walking, running, and jumping. Unfortunately, playing sports increases your risk of developing foot or ankle injuries. If you have sports injuries that affect your feet or ankles, the experienced team of board-certified podiatrists at Brandywine Foot and Ankle Associates can help. They diagnose and treat sports injuries and make recommendations to prevent a recurrence of your foot or ankle injury. Call one of the offices in Coatesville, and Limerick, Pennsylvania, or book an appointment online today. Physical activity is good for your health; however, accidents happen. Though you can injure any body part when playing a sport, your feet and ankles are most susceptible to sports injuries because of the stress they endure during physical activity. Types of foot and ankle sports injuries include: The sports injury experts at Brandywine Foot and Ankle Associates see a lot of athletes, especially basketball and soccer players, with ankle sprains. Failing to get the proper care for an ankle sprain may increase your risk of developing chronic ankle problems. The Brandywine Foot and Ankle Associates team recommends you schedule an appointment with the podiatry experts right away. Delaying care for your sports injury may worsen your condition, slow healing, and prolong your recovery. It’s especially important to seek care for your sports injury if it causes severe pain, swelling, or a noticeable deformity. Brandywine Foot and Ankle Associates offers emergency podiatry care to help you get treatment for your sports injury as quickly as possible. The podiatrists at Brandywine Foot and Ankle Associates conduct comprehensive evaluations when you come in with a sports injury involving your foot or ankle. Your podiatrist asks detailed questions about your injury, including when and how it happened and your symptoms. They also ask about your sport and workout routine. Your podiatrist examines your feet and ankle, checking your range of motion and looking for areas of tenderness. They may also request X-rays to confirm or rule out a diagnosis. Your podiatrist creates a personalized treatment plan for your sports injury based on injury type and severity of symptoms. Treatment may include: When nonsurgical treatments fail to improve your foot injury, the team may suggest surgical intervention. If you have an Achilles rupture or complex foot or ankle fracture, the team may start with surgery. Most importantly, the podiatrists at Brandywine Foot and Ankle Associates work closely with you to prevent a recurrence of your sports injury, recommending specific shoe wear and exercises to better support your feet and ankles during physical activity. Sports injuries to your feet or ankles benefit from expert care at Brandywine Foot and Ankle Associates. Call or schedule a consultation online today.

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What is an ankle sprain? A sprained ankle is a very common ankle injury. A sprain involves stretching or tearing of the ankle ligaments. The most common is an inversion injury where the ankle turns inward, injuring the ligaments on the outside of the ankle. The most common injury sustained in a sprained ankle is to the anterior talo-fibula ligament (ATFL). (See figure) If the sprain is severe there might also be damage to the calcaneo-fibula ligament (CFL) (See figure). In addition to the ligament injury there may also be injury to tendons, bone and other joint tissues, which is why it is important to get an accurate diagnosis of your ankle sprain. Severe ankle sprains may be associated with a fracture. Ankle Sprain Treatment Establishing an accurate diagnosis from the start is important. The treatment will be different if there are associated fractures or other injuries. RICE (Rest, Ice, Compression, Elevation) as soon as possible. R is for rest. It is important to rest the injury to reduce pain and prevent further damage. Crutches may be needed if there is severe pain when putting weight on the injured side. I is for ICE. Applying ice and compression can ease the pain and reduce swelling. Apply an ice pack wrapped in a towel immediately following injury for 15 minutes. Repeat this every 4 hours. C is for compression - This reduces bleeding and helps reduce swelling. Elastic bandaging is excellent for providing support and compression. E is for Elevation - Uses gravity to reduce bleeding and swelling by allowing fluids to flow away from the site of injury. Protect the injured ankle with an ankle support. Tape can also be used during the rehabilitation phase to protect the joint and give proprioceptive feedback to the ankle to decrease further injury. What we can do? A sports medicine physician can assess the injury to establish an accurate diagnosis. Pain medications can be prescribed to help with pain and swelling. Sports physiotherapist can help with: Swelling reduction by compression, massage, or taping techniques. Prescribe a full ankle rehabilitation programme to strengthen the joint and help prevent future ankle sprains by improving balance and proprioception.

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Welcome to the next installment in the Tread & Butter Foot Health Journal: how to reduce pain and heal shin splints through stretches, exercises, and general foot health! For this article, we’re continuing the deep-dive journey into foot health to bring you the latest information on how to heal shin splints and reduce shin splint pain—all through good foot health, the right arch support, and targeted stretches and exercises for shin splints. Much like we did in our previous article on plantar fasciitis, we’ve spoken with yet another experienced physical therapist in Bend, Oregon, and asked him how foot health can help reduce shin splint injuries. We then took what we learned from our conversation about the close relationship between shin splints and foot health, and combined it with our own background and research in arch support and insoles. The result? This little shin splints guide for your reading pleasure. So, happy shin-splint healing, y’all. And be sure to check out all the other useful feet-first articles from our ongoing Foot Health Journal. Shin splints. What are they and what causes them? As people who exercise and roam and move our bodies, we’ve all heard of and/or experienced shin splints at some point or another. If pressed, though, could you clearly explain what causes shin splints and what occurs when you experience them? Don’t worry, before we started designing arch support and insoles for shin splints, we wouldn't have been able to explain it either. But now, now we know the basics of shin splints like the bottom of our feet. And we’re happy to share what we’ve learned with you. To keep it simple, let’s start with the fact that shin splints are very common and very related to exercise. As a term and a sensation, shin splints are defined by an experience of pain along the tibia (the inner edge of the shinbone). They also usually develop post-exercise or following some kind of physical activity—most often running, walking, or jogging. Yes, it’s true that shin splints are typically associated with running (track, road, or trail). But it’s also true that any kind of vigorous exercise—from hiking and skiing, to tennis, soccer, dancing, and beyond—can bring on shin splints. Especially if you’re starting from scratch, relatively speaking, or going from zero to one hundred in terms of intensity, volume, or duration. Scientifically speaking, and according to the American Academy of Orthopaedic Surgeons, shin splints are caused by an “inflammation of the muscles, tendons, and bone tissue around your tibia.” Technically known as medial tibial stress syndrome, shin splints “typically occur along the inner border of the tibia, where muscles attach to the bone.” While shin splints can be attributed to a number of factors, they most commonly occur when you overwork the muscle and bone tissue in your leg through repetitive activity. Basically, whenever you make a sudden change to your activity levels and either increase the intensity or volume or duration of your exercise routine, you increase the chances of developing shin splints. Other structural and environmental factors that can contribute to causing shin splints include: To help give you an idea of what shin splints feel like, and determine whether or not you’re experiencing pain as a result of them, we’ve compiled a handy list of common shin splint symptoms and indications. Remember, the area we are zoning in on for shin-splint detection is located along your tibia, where the muscle and tissue meet the shin bone. While you should always consult a professional about what’s actually going on, some things you’ll most likely experience if you’ve found yourself face to face with some good old fashioned shin splints are: We’ll hear from Grant Carson, the local physical therapist we spoke with regarding the correlation between foot health and shin splints shortly, but for now: let’s get proactive. And by proactive we mean let’s take a look at a few key exercises and stretches for shin splints so you can start weaving them into your routine. Along with other essential shin splint stretches and exercises, these ones are a big part of the proactive picture that’s going to help you heal, treat, and prevent shin splints. *Some Quick Notes: Rest is an important part of any healing process—always include rest! Also, always warm up before starting any of the following shin splint stretches; for video tutorials on some of these, we like what we see over at Healthline, The Prehab Guys and The Stretch Coach (No, we don’t know Mr. Stretch or those Prehab dudes. But we like their styles and their credentials.). If you’re unsure of what to do or where your pain is really coming from, please consult a trusted professional. (adapted from: Healthline) (source: Stretch Coach) (adapted from: Prehab Guys) This seated ankle dorsiflexion stretch for shin splints is a great way to train the dorsiflexors of the foot/ankle complex (which is often a culprit of shin splints). Remember to focus on slowly lowering the weight back towards the floor to gain the biggest benefit from this movement. (adapted from: Healthline) As we’ll hear from Grant in the next section, shin splint treatment and prevention isn’t just about stretching the shin and calf area. Our shins are only part of the larger system that is our bodies, and so shin splints can’t be addressed without looking at things like core imbalances and hip muscles. Core imbalances can lead to lower-extremity injuries, and hip muscles are what help stabilize the pelvis during running and walking. Neither should go overlooked when treating shin splints. Don't let shin splints harsh your mellow. Photo: Adobe OK, now let’s talk about how to prevent shin splints through good foot health, and let’s at last talk about it with physical therapist Grant Carson! Grant, what are your thoughts on shin splints and foot health? “Hey! Thanks for having me. OK, so when I treat people, whether for shin splints or some other issue, I emphasize the deconstruction of symptoms that are driving a pattern. Like, if you go to a therapist and they only look at your feet when your foot is hurting, they are missing the bus. It’s the whole picture that needs to be looked at, the whole chain reaction from head to toe. What I’m getting at here is that shin splints are never just about our shins, calves, and lower legs. They’re about our hips and pelvis, our core and our feet—and about our overall foot health.” We touched on that a little earlier, but, how so? “Your feet and your hips are partners—they control rotational movement. If your feet and hips (hinge and sagittal plane joints) aren’t functioning like they could or should, then it’s your knees and back (and potentially your shins) that pay for that. For some time I worked for the Louisville Ballet and, yes, dancers are very prone to shin splints—much of what I saw had to do with both footwear (ballet shoes are brutal), overuse, and the correlation between hip muscles and rotational movement.” OK, well, I know ballet dancers put their feet through the ringer. But how important is proper-fitting footwear for us mere mortals? “Basically, it’s important to keep in mind that what feels good walking around at the store is not necessarily appropriate. There are a lot of slipper-like tennis shoes and running shoes out there, but most people don’t have the ligament strength to walk around in them all day, let alone run in them. While I'm a big believer in doing body-weight exercises barefoot (for balance, proprioception, and strength-building), I do not recommend heavier weights or advancing rapidly with plyometrics without proper foot support. All of which leads me to this: When we’re talking about the long game (of life and overall body health and function), orthotics and footwear are pretty important. You don’t have to feel like you need to stick to one type of shoe or brand or insole shape, though. Like most things in this world, it’s good to mix it up, to see what works according to where your body’s at in its stage of life.” Adapt and thrive (or at least feel better)—that makes sense. Thanks so much for talking with us, Grant. Your wisdom regarding foot health and shin splints is very much appreciated. Need help reducing or preventing shin-splint pain? With shin splints, we know there’s no singular solution to prevention or treatment. Rather, the best shin splint prevention and treatment is about a confluence of actions, including rest and the right exercises and stretches. And the best arch support for your (unique) feet. To see how Tread & Butter can change your world from the ground up, check out our high arch and low arch cork insolesor send us a note about your specific insole needs. We’re always here to inform, support (literally), and help you say goodbye to shin splints. Grant Carson is the owner and physical therapist guru behind Tumalo Wellness in Bend, Oregon. As someone with more than 20 years of experience delivering physical therapy to elite athletes, major sports teams, and mere mortals alike, Grant is well-versed in helping people (and feet) re-pattern themselves away from pain and towards healing. Got questions? Give him a shout or book a PT session, and be sure to tell him we sent you.

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A heel spur is a hook that can form on the calcaneus (heel bone) and can also be related to plantar fasciitis (inflammation of the tissue in the foot?s arch). People who have plantar fasciitis often develop heel spurs. Middle-aged men and women are more prone to heels spurs, but all age groups can be afflicted. Heel spurs can be found through an x-ray, revealing a protruding hook where the plantar fascia is located. Heel spurs form in some patients who have plantar fasciitis (PLAN-tar fash-ee-I-tis), and tend to occur in patients who have had the problem for a prolonged period of time. While about 70 percent of patients with plantar fasciitis have a heel spur, X-rays also show about 50 percent of patients with no symptoms of plantar fasciitis also have a heel spur. More often than not, heel spurs have no signs or symptoms, and you don?t feel any pain. This is because heel spurs aren?t pointy or sharp pieces of bone, contrary to common belief. Heel spurs don?t cut tissue every time movement occurs; they?re actually deposits of calcium on bone set in place by the body?s normal bone-forming mechanisms. This means they?re smooth and flat, just like all other bones. Because there?s already tissue present at the site of a heel spur, sometimes that area and the surrounding tissue get inflamed, leading to a number of symptoms, such as chronic heel pain that occurs when jogging or walking. Heel spurs and plantar fasciitis is usually diagnosed by your physiotherapist or sports doctor based on your symptoms, history and clinical examination. After confirming your heel spur or plantar fasciitis they will investigate WHY you are likely to be predisposed to heel spurs and develop a treatment plan to decrease your chance of future bouts. X-rays will show calcification or bone within the plantar fascia or at its insertion into the calcaneus. This is known as a calcaneal or heel spur. Ultrasound scans and MRI are used to identify any plantar fasciitis tears, inflammation or calcification. Pathology tests may identify spondyloarthritis, which can cause symptoms similar to plantar fasciitis. Non Surgical Treatment Heel spurs and plantar fascitis (inflammation of the plantar fascia) are usually controlled with conservative treatment. Early intervention includes stretching the calf muscles while avoiding reinjury to the plantar fascia. Decreasing or changing activities, losing excess weight, and improving the fit of shoes are all important measures to decrease foot pain. Modification of footwear includes well-padded shoes with a raised heel and better arch support. Shoe inserts recommended by a healthcare professional are often very helpful when used with exercises to increase the strength of the foot muscles and arch. The inserts prevent excessive pronation and continued tearing of the plantar fascia. Have surgery if no other treatments work. Before performing surgery, doctors usually give home treatments and improved footwear about a year to work. When nothing else eases the pain, here's what you need to know about surgical options. Instep plantar fasciotomy. Doctors remove part of the plantar fascia to ease pressure on the nerves in your foot. Endoscopy. This surgery performs the same function as an instep plantar fasciotomy but uses smaller incisions so that you'll heal faster. However, endoscopy has a higher rate of nerve damage, so consider this before you opt for this option. Be prepared to wear a below-the-knee walking cast to ease the pain of surgery and to speed the healing process. These casts, or "boots," usually work better than crutches to speed up your recovery time. Walk around before you buy shoes. Before you purchase your shoes, do the following. Re-lace the shoes if you're trying on athletic shoes. Start at the farthest eyelets and apply even pressure to the laces as you come closer to the tongue of the shoe. Make sure that you can wiggle your toes freely inside of the shoe. Also, make sure that you have at enough space between your tallest toe and the end of the shoe. You should have room equal to about the width of your thumb in the tip of your shoe. Walk around to make sure that the shoe has a firm grip on your heel without sliding up and down. Walk or run a few steps to make sure your shoes are comfortable. Shoes that fit properly require no break-in period.

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Results of total ankle arthroplasty. Most published reports related to total ankle arthroplasty have a fair to poor-quality level of evidence. Comparative studies with a fair to good-quality level of evidence suggest that total ankle arthroplasty provides equal pain relief and possibly improved function compared with ankle arthrodesis. On the basis of the current literature, survivorship of total ankle arthroplasty implants, when measured as the retention of metal components, ranges from 70% to 98% at three to six years and from 80% to 95% at eight to twelve years. Several investigators have argued that, in the evolution of total ankle arthroplasty, some obligatory reoperation without removal of the metal implants is anticipated; examples of reoperation include relief of osseous or soft-tissue impingement, improvement of alignment or stability of the foot and ankle, bone-grafting for cystic lesions, and/or polyethylene exchange. A successful return to low-impact, recreational sporting activities is possible after total ankle arthroplasty. Easley, ME; Adams, SB; Hembree, WC; DeOrio, JK Volume / Issue Start / End Page Electronic International Standard Serial Number (EISSN) Digital Object Identifier (DOI)

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Plantar fasciitis and heel pad syndrome are two common causes of foot and heel pain. Both can be caused by sudden increases in walking or running. The two conditions require completely different treatment approaches. But before treatment can begin, the cause of the heel pain needs to be identified. There is a simple diagnostic test that can be performed by your chiropractor, physio or healthcare professional that’ll help differentiate between the two conditions and allow them to modify your treatment plan appropriately. But before we discuss how to tell the two conditions apart, let’s review each condition in a little more detail. What is the plantar fascia? The plantar fascia is a thick connective tissue that runs from your heel (calcaneus) to the bones in your midfoot called your metatarsals. It’s made up of strong collagen fibres that support and maintain the arch of the foot during the gait cycle. The plantar fascia is extremely important for walking and running. Studies have found that the plantar fascia rapidly elongates while your foot is in contact with the ground and recoils like a spring during toe-off. When the big toe is dorsiflexed (pulled upwards) it tensions the plantar fascia, this is known as the “windlass mechanism” and is vital for proper walking or running mechanics. The plantar fascia is hi-lighted in blue. Plantar fasciitis, fasciosis or fasciopathy? Plantar fasciitis results in pain in your heel or foot due to degenerative changes of the collagen fibres that form the plantar fascia. We use the term fasciitis, “-itis” which would imply that this is an inflammatory condition. However, this is incorrect as there are no inflammatory cells present in the tissue. The correct term that should be used is plantar “fasciopathy” or “fasciosis”. To prevent confusion, I’ll refer to it as plantar fasciitis in this article as this is The term fasciosis “-osis” means destruction or degeneration. Fasciopathy “-opathy” has become the go-to term because it means that there is a “disease or disorder” of the tissue that could include both inflammatory and/or degenerative changes, which we know is the case in this condition. What is the heel pad? The heel fat pad is a collection of adipose (fat) tissue that surrounds your calcaneus (heel bone). Its function is to absorb the impact between your heel and the ground during walking, running and jumping. The impact between your heel and the ground is highest during the foot-strike phase of the gait cycle. The heel needs to be able to absorb 110% of the body’s weight during walking and up to 200% during running. The fat pad is the tissue structure underneath your heel. What is heel pad syndrome? Heel pad syndrome causes pain in your heel due to inflammation and/or destruction of the fatty tissue that surrounds your calcaneus (heel bone). It is the second most common cause of foot pain after plantar fasciitis. The fat pad can become inflamed due to participation in sports that require a lot of jumping such as volleyball, gymnastics or athletics. An excessive increase in your running distance each week can also increase your risk of heel pad syndrome. Click here to read our blog post that explores ways in which you can manage your training load and prevent running-related injuries. Do I have plantar fasciitis or heel pad syndrome? Both plantar fasciitis and heel pad syndrome can cause heel pain. A quick test that can be done to differentiate between the two is simply walking on your toes. When walking on your toes, if your heel pain increases then that would suggest that your plantar fascia is the source of pain. That is because walking on your toes causes your big toe to dorsiflex (bend upwards) which increases the tension in the plantar fascia. If there is degeneration of the collagen fibres of the plantar fascia, it’s going to be painful when that tissue is loaded. But if you were to walk on your toes and notice a reduction in heel pain, that would indicate that your heel pad is the source of the pain. The reason is simple, by walking on your toes you’ve taken all the pressure off your inflamed heel fat pad. Starting position for the calf raise test An increase in heel pain in this position would suggest that plantar fasciitis is the diagnosis. How do we treat these conditions? It’s not uncommon to see cases of heel pad syndrome and plantar fasciitis as a result of overuse or overtraining. That’s why it’s vital to identify if there have been changes to somebody’s training routine that could have increased the load placed on the tissues. Biomechanical abnormalities of the core, hip, foot & ankle can also be responsible for causing plantar fasciitis or heel pad syndrome. These abnormalities can alter the way a person’s weight is distributed throughout their foot during the gait cycle, leading to an overuse injury. Plantar fasciitis treatment: To treat plantar fasciitis we need to create an environment in the foot that promotes the synthesis and repair of the damaged collagen fibres. Remember, we know that it’s not a true inflammatory condition but rather a degenerative condition. To help increase the rate of collagen repair in the plantar fascia we need to create micro-trauma and restart the body’s repair process. My go-to method for treating this is by using a combination of extracorporeal shockwave therapy and manual therapy of the hip, foot and ankle. Rehabilitation exercises that gradually increase the load in the plantar fascia are also prescribed as exercise has been shown to stimulate collagen synthesis. Taping the arch of the foot with dynamic tape or rigid athletic tape can be used to support the arch of your foot and offload the painful plantar fascia. Heel pad syndrome treatment When treating heel pad syndrome we do the opposite of what we do for plantar fasciitis. Heel pad syndrome is most often a true inflammatory condition. Treatment needs to decrease inflammation of the fat pad. A treatment method like shockwave therapy would make your heel pain worse as it promotes an inflammatory response in tissues. A taping technique can be applied to essentially compress the fat pad of the heel. This can reduce a persons heel pain and make normal walking more bearable. You can help speed up your recovery time by wearing shoes with proper cushioning and limiting the amount of time you walk barefoot. Our chiropractors at Prime Health Co. can assist in your recovery from heel pad syndrome or plantar fasciitis. The first step (no pun intended) in your recovery is a proper diagnosis as the two conditions require different kinds of treatment and rehabilitation. Next, we will discuss the best methods of treatment to decrease your heel pain and put a rehabilitation program together that’ll improve your resistance to future reoccurrences.

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Our poor, overworked feet. In a single day, they absorb about 1,000 pounds of force. And we mistreat them terribly -- standing on them for hours; walking on hard, unyielding surfaces; and cramming them into shoes that may be fashionable but are often far from comfortable. It's no wonder that four out of five adults eventually suffer from foot problems. While certainly not as glamorous as the heart or the brain, the feet are amazing pieces of engineering, perfectly designed to give years of service -- if you treat them right. Each foot has 26 bones -- together the feet have almost one-quarter of the bones in the entire body. Thirty-three joints make the feet flexible, and 19 muscles control movement of foot parts. Tendons stretch tautly between muscles and bones, moving parts of the feet as the muscles contract. Two arches in the midfoot and forefoot, constructed like small bridges, support each foot and provide a springy, elastic structure to absorb shock. Numerous nerve endings in the feet make them sensitive (and ticklish). And the whole structure is held together by more than 100 ligaments. Much of the foot pain we experience comes from overworked lower limbs. Movement of the foot is controlled by four groups of muscles in the leg. These muscles get a workout not only when our feet are visibly moving (such as when we walk or run) but even when we stand still, because they help keep us balanced and upright. And like nearly all muscles (the heart muscle is an exception), these muscles can become fatigued, decreasing their ability to properly support the feet and causing discomfort. Standing in place for long periods also tends to result in a pooling of blood in the lower extremities, which can cause uncomfortable swelling. Here are some common problems that cause foot pain, most often due to an overuse injury. Plantar fasciitis. A heel injury, affecting the area where the arch meets the heel. Plantar fasciitis is marked by heel pain with first steps in the morning, possible swelling, and heel pain while walking. It can usually be worked out with activity. What to do: Wear better shoes, or try orthopedic shoes prescribed by a podiatrist. Don't walk barefoot. Use ice unless you have circulatory problems or are diabetic. Try heel cups in your shoes for shock absorption. If the pain is persistent, see a podiatrist. Heel spurs. A little outgrowth of the bone, a result of the bone's attempt to heal after repetitive stress and inflammation in the plantar fascia. What to do: If it causes foot pain, a simple surgery to shave the spur away may be required. Neuroma. A pinched nerve, causing pain between the third and fourth toes. It can feel like a tooth that needs a root canal. One of the most common causes is a poor shoe fit. What to do: Buy a shoe with a wider toe area. Tendonitis. An inflammatory process in the tendons, common in athletes. It can be a serious, painful, and persistent problem. What to do: Rest, ice, use anti-inflammatory drugs, and change exercise technique and shoe gear. Stress fracture. A break in the bone usually resulting from repetitive pounding. Common to athletes. What to do: Limit weight bearing, and stick to low impact exercise. An orthotic device may be necessary to reduce pressure at the fracture site. Be sure to confirm and locate the stress fracture via X ray for proper treatment. Ankle sprains. A ligament that is stretched or torn. It is the most common athletic injury. What to do: Ice, compression with an elastic bandage or splint to eliminate motion, and elevation to decrease swelling. Limit weight-bearing activities, and stay off feet for a few days. In cases of a severe sprain, your podiatrist may recommend a brace or surgery. Here are a few more foot aches that aren't attributed to overuse. Instead, these are caused by simple everyday wear and tear, as well as poorly fit shoes. Black toenail. A hematoma (bruising) under the nail. What to do: Wear proper-fitting shoes that aren't too tight or too loose, clip toenails short so they won't rub against the shoe, soak foot in salt water. Bunions. A misaligned big toe joint in which the toe slants outward causing inflammation and swelling. The most common cause is tight-fitting shoes. What to do: Wear proper-fitting shoes and padding, and rest and soak the foot. Bunions must be treated by a podiatrist Hammertoe. When a toe, usually the second toe, bends up to look like a claw. It frequently accompanies a bunion, and while the actual cause is a muscle imbalance, the underlying cause of that imbalance is usually an ill-fitting shoe that cramps the toes. What to do: Wear proper-fitting shoes and padding. Hammertoes must be treated by a podiatrist Ingrown toenail. This happens when the side of your toenail cuts into your skin. The cause is usually a bad toenail clip job, but pressure from a bad shoe fit can cause it, too. A mild ingrown nail can be removed with careful clipping, but if it is deep or painful, consider a trip to the podiatrist. Bad Shoes, Good Shoes Bad shoes are what many foot injuries have in common. Bad shoes, according to the American College of Foot and Ankle Surgeons, are to blame for about 90 percent of all foot problems. No matter what type of shoe you're wearing, a bad shoe is one that does not fit properly, has lost its shape, causes pain or rubbing, or is worn unevenly. Bad shoes cause foot and ankle problems. But they can cause leg and back problems, too. To get a good fit for any type of shoe: - Buy shoes at the end of the day, after work or exercise, when your feet are at their largest. If you buy shoes earlier in the day, they may be too tight. - Measure both feet and fit your shoe to the largest one, since your feet aren't both the same size. - Make sure you can wiggle your toes. If you can't, the fit is too tight. Also make sure the widest part of your foot is comfortable but secure. - Walk around the store to see if the shoes are comfortable. Never buy shoes without first trying them on, and don't assume they will get comfortable with wear. If they don't feel good when you try them on, don't buy them. - Try on shoes with the socks you plan to wear with them. - When the shoe is on and you're standing up, make sure you can fit the width of your little finger between your heel and the back of the shoe -- no more and no less. - If your heel slides in the shoe as you walk, the shoe doesn't fit. - Don't let anyone tell you the shoe will stretch. Good shoes fit properly when you buy them. - And, no matter how much you're attached to your closet full of comfortable old shoes, toss them in the trash when they are worn out and get new ones. Now that you know what that foot pain might be, as well as possible treatment options, here are a few home remedies to help heal those tired, aching dogs. Visit these links to learn more about home remedies for foot ailments: - To see all of our home remedies and the conditions they treat, go to our main Home Remedies page. - Read Home Remedies for Back Pain to learn about home remedies that will help your aching back. - If you're dealing with a serious case of foot funk, learn how to banish the odor in Home Remedies for Foot Odor. - Learn how to stop the uncomfortable itching and burning of athlete's foot in Home Remedies for Athlete's Foot. - Learn how to use natural home remedies to ease the discomfort of corns and calluses in Home Remedies for Calluses and Corns. This information is solely for informational purposes. IT IS NOT INTENDED TO PROVIDE MEDICAL ADVICE. Neither the Editors of Consumer Guide (R), Publications International, Ltd., the author nor publisher take responsibility for any possible consequences from any treatment, procedure, exercise, dietary modification, action or application of medication which results from reading or following the information contained in this information. The publication of this information does not constitute the practice of medicine, and this information does not replace the advice of your physician or other health care provider. Before undertaking any course of treatment, the reader must seek the advice of their physician or other health care provider.

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As anybody with bunions will know, the condition can be pretty painful. Your toe is often swollen, red, and tender to the touch. This can make it difficult to wear comfortable footwear, perform daily tasks such as shopping or exercising, and even disrupt your sleep schedule. But when left untreated, can bunions cause leg pain as well? Here’s everything you need to know. Why Do Bunions Hurt in the First Place? You may be asking yourself, “can bunions cause leg pain, too?” It’s a fair question to ask, but why are bunions so painful to begin with? Bunions are essentially a misalignment of the joints in the toes. These misalignments can create a boney bump on the side of the foot that can be very painful. Aside from the pain of the lump, the misalignment itself can leave the toe stiff, as well as make it much more difficult to walk, run, stand, or even sit comfortably. This puts pressure on the joints and muscles over time, making the entire process uncomfortable. Can Bunions Cause Leg Pain? Unfortunately . . . So, can bunions cause leg pain in addition to foot pain? Unfortunately, bunions can indeed cause leg pain in some people. This is mostly due to the fact that your walking and standing patterns will begin to change in an effort to transfer the pressure off your bunion, but in doing so the pressure can build up in your calf muscles and thighs. This can create aches and pains in the leg, and in some cases, cramps can occur. If you’re experiencing leg pain, there’s no reason to worry. There are several things you can do to stop the pain from getting worse. How to Stop the Pain Can bunions cause leg pain? Yes, but regardless of whether the pain has spread to your legs or has remained in your foot, pain is pain. It never feels good. Luckily, you’ve got a few options to manage the pain. If you’re walking around without insoles designed specifically to cushion your step or don’t have your own bunion guard, getting these tools can drastically reduce the pressure and minimize those stabbing pains that shoot up your leg as well. Other methods include sleeping with your foot elevated, taking certain medications, and performing daily toe and foot stretches. However, if you’re looking for a way to get rid of the pain completely, the only way to do so is through surgery. At Northwest Surgery Center, we perform minimally invasive bunion surgery to get our patients back to their lives with as few complications as possible. Deal With Your Bunions Once and for All Nobody enjoys dealing with bunions; they’re painful, annoying, and can affect other aspects of your life in negative ways. But just because you currently have bunions doesn’t mean you’re forced to live with them forever. It’s time to deal with your bunions once and for all by getting minimally invasive surgery. By connecting with the medical professionals at Northwest Surgery Center, you can begin moving towards living the life you had before bunions. Ready to take the first step? Contact us today or call 414-246-9416 to learn more.

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A stress fracture is a small fracture in the bone, often referred to as a hairline fracture. Stress fractures can occur in any bone in the body; however the most common location is in the feet, where the weight of the body is concentrated. They are often considered a problem of overuse usually resulting from high impact sports, over training, or undertaking activities to which the body is not conditioned. Weakening of bones can occur at any age and the most common locations of a stress fracture are the second and third metatarsals; the long bones which run down to the toes. They can also occur in the heel and in the navicular bone, at the top of the midfoot in front of the ankle. There are many treatment options available to repair your stress fracture and relieve your pain. Call Northern Foot & Ankle today and set an appointment with one of our board certified podiatrists to review your treatment options. Your feet don’t have to hurt.

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The Achilles Tendon: What is it? The location of the Achilles tendon insertion point is shown in a foot anatomy diagram. The band of tissue that runs down the back of the lower leg, linking the calf muscle to the heel bone, is the Achilles tendon, where Achilles tendon problems manifest. The Achilles tendon, often known as the heel cord, aids in walking by helping to lift the heel off the ground. Tendonitis and osteonecrosis of the Achilles Achilles tendonitis and Achilles tendinosis are two conditions that frequently affect the heel cord medical term for inflammation of the Achilles’ tendons is “Achilles tendonitis.” Usually, this inflammation subsides quickly. However, if the problem is not treated, it could eventually lead to Achilles tendinosis. In this tendon degeneration, the tendon loses its perfectly ordered structure and is more susceptible to experiencing microscopic rips. Occasionally, the region where the Achilles tendon attaches to the heel bone can deteriorate. However, rarely can tendon rupture occur by persistent deterioration with or without pain. Disorders of the Achilles tendonitis causes Achilles tendonitis and tendinosis are “overuse” illnesses typically brought on by an abrupt increase in an Achilles tendon-related repetitive activity. Such exercise causes micro-injury to the tendon fibers because it overstretches them too quickly. The body cannot repair the damaged tissue due to this constant strain on the tendon. The structure of the tendon is subsequently changed, which causes the discomfort to persist. Achilles tendon diseases can be quite dangerous for athletes. Additionally, laborers who regularly strain their ankles and feet and “weekend warriors”—those who are less fit and engage in athletics only sometimes or on the weekends—are prone to developing Achilles tendonitis and tendinosis. Additionally, due to the increased pressures placed on the Achilles tendon when walking, individuals with severe pronation (flattening of the arch) are more likely to get Achilles tendonitis and tendinosis. If these people wear unstable shoes, their overpronation could exacerbate their Achilles tendon problems. Achilles tendonitis disorders symptoms The following are the signs of tendinitis and tendinosis of the Achilles tendonitis: Internal tendon pain, including aching, stiffness, tightness, or tenderness. This could happen anywhere along the tendon’s course, from the area below the calf muscle to where the tendon attaches directly above the heel. Pain frequently starts when you wake up in the morning or after a period of rest, then it becomes a little better with movement, but it worsens with more action later. When the tendon’s sides are squeezed, there may be tenderness or severe pain. But when you press straight on the tendon’s back, there is less pain. The tendon may swell up and produce nodules where the tissue is injured as the condition advances to degeneration. Diagnosis of disorders of the Achilles tendonitis The surgeon will check the patient’s foot, ankle, and range of motion to determine whether the tendon has tendonitis or tendinosis. X-rays or other imaging modalities can be used to determine the severity of the illness. Disorders of the Achilles tendonitis treatment Depending on how long the injury has been present and the extent of the tendon damage, treatment methods for Achilles tendonitis or tendonosis are chosen. When an inflammation appears suddenly (acutely) in the early stages, one or more of the following options may be advised: - Immobilization. To lessen forces through the Achilles tendon and encourage recovery, immobilization may involve using a cast or removable walking boot. - Ice. Apply a tiny towel-wrapped ice pack to the area to the affected area for 20 minutes every hour you’re awake to reduce swelling brought on by inflammation. Never apply ice to the skin directly. - Drugs taken orally. In the early stages of the illness, nonsteroidal anti-inflammatory medications (NSAIDs), including ibuprofen, may be useful in lowering pain and inflammation. - Orthotics. Custom orthotic devices may be prescribed for people with overpronation or gait disorders. - Night braces. The Achilles tendon is stretched as you sleep, thanks to night splints. When is surgery necessary? Surgery can be required if nonsurgical methods fail to return the tendon to its healthy state. The surgeon will consider the injury’s degree, the patient’s age and activity level, and other considerations while deciding the best approach to repair the tendon. After surgical or nonsurgical therapy for Achilles tendonitis or tendinosis, the foot and ankle surgeon could advise regular calf muscle stretching and strengthening exercises to prevent a recurrence. Another significant factor in keeping the problem from returning is wearing the right shoes for your foot type and activity. Contact Bayshore Podiatry for Achilles tendonitis At Bayshore Podiatry, the Podiatry team handles everything from the straightforward to the complex patients of all ages; they can treat anything from fungal toenails to foot surgery. If you have any questions, please feel free to contact our office located in Tampa, FL. You can also use our online form to request an appointment.

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Read more to discover what custom orthotics are and how they’re the best investment for your foot health. Custom orthotics are a prescription orthotic made from a 3D impression of your feet. They’re made just for you to help improve, support or correct your foot posture or treat any foot pathology you may be experiencing. Many injuries and conditions we see at our foot clinics occur as a consequence of abnormal foot and lower limb mechanics. Such abnormalities can have a significant impact on the feet, legs, pelvis and spine. Custom orthotics are specifically designed to suit your particular condition, foot type, weight and desired activity. Generally, custom orthotics offer greater control than other types of orthotics, in addition to being more durable. Biomechanical correction is achieved by using high density foams and plastics which initially may appear too rigid but, in time, usually become quite comfortable. Research has shown that, in many cases, custom orthotics can relieve pain and prevent further disability. That said, not everyone is a candidate for orthotic therapy. We also specialise in footwear prescription; frequently, some simple advice is all that is needed. You can rest assured we will only recommend custom orthotics when necessary. Orthotics are used to treat numerous foot conditions. Depending on which condition you have, the design and the features of the device will help provide you with the best treatment outcome. Orthotics are never a standalone treatment, and your Podiatrist will recommend footwear changes, exercises and in some cases medication as well. Here are some examples of foot conditions that can be treated with orthotics: Custom orthotics are specially-made devices designed to support and comfort your feet. Schedule an appointment today with a Podiatrist to be assessed and see if orthotic therapy is a solution for you. How are custom orthotics made? Making custom orthotics is a multi-step process that first begins with a thorough assessment by a podiatrist. During this assessment, your podiatrist will ask how and when your symptoms started. After that, your podiatrist will do a foot examniation. This assessment of your feet usually includes a visual gait assessment. If you require any additional imaging for your feet to assess an underlying pathology (such as X-ray or ultrasound), your podiatrist will refer you. Factoring in your symptoms, pathology, activity and footwear, your podiatrist will design an orthotic for your individual needs. Your prescription is then sent to a state-of-the-art orthotic laboratory where it’s hand made by highly skilled technicians. Custom orthotics can differ not only in the materials used but also in their shape. Depending on your foot condition, activity and what footwear you would like to put them in, the prescription will change. Options include: Our patients always ask us this question and feel that as Podiatrist we should be able to answer it as best as possible. The goal of orthotic therapy is to reduce internal and external forces which are acting on specific parts of foot, with the goal to treat injury and reduce foot pain. Orthotics alter pressure coming from the ground to the foot (ground reaction force) when you stand, walk or run. By altering these forces we can achieve better foot function and reduce any excessive forces that lead to foot injury. Depending on pathology and where your foot pain is located, different orthotic design with specific features can change location, magnitude and timing of force acting and within the foot. These excessive forces inside the foot and ankle are the cause of nearly all mechanically related injuries that we treat on a daily basis. By wearing orthotics, we can help send back sensory feedback to your brain to prompt it to change its movement during gait. With these signals your brain can send corrective movements to the foot and improve function, avoid pain and prevent injury. Custom made orthotics are crafted for you and no one else. Following an assessment by a Podiatrist a pair of custom made orthotics will be made to accommodate your unique foot structure and pathology. Depending on your policy, if you are covered for podiatry and orthotic services, you may be eligible for a rebate on your orthotics. Before you consider having custom orthotics made, you’ll want to check to see how much your insurance will cover and what your out-of-pocket expenses are. Find below detailed item codes*: Visual gait analysis, footwear assessment, assessment for orthotic therapy (item codes: 004, 118) Scans of feet to make custom orthotics (item codes: 301, 301) 1 pair of custom orthotics and a short fitting appointment (item codes: 221, 221, 010) 2 pairs of custom orthotics and a short fitting appointment (item codes: 221, 221, 221, 221, 010) Orthotic review (item code: 012) * Please be aware item codes vary across different health funds. You can also take advantage of your private health insurance and our second pair discounts and get additional pairs each year for different shoes or activities when it resets annually. At The Foot Hub, we know that custom orthotics aren’t without their controversy. A common story we hear is: Unfortunately, some people have had experiences like this before. This something we try to avoid in our Sydney foot clinics with the following practices: At The Foot Hub we pride ourselves in delivering accurate and meticulous custom made orthotics to our patients. We promise the following to our patients: Discounts on additional pair Australian owned company Six weeks following an orthotic fitting, your podiatrist will make a follow up appointment to see how your orthotics going. Custom orthotics should be gradually worn in overtime starting off with an hour a day increasing until you are able to wear them all day with no discomfort. These appointments are a crucial step, and we advise our patients to make sure to attend them. At The Foot Hub, we assure all our patients that should anything cause significant pain to promptly call the clinic. If any modifications are required to the orthotic at this appointment, these will be free of charge. Getting your orthotics right is important to us. Shoes are essential when it comes to orthotic function. Wearing proper fitting orthotic-friendly shoes you can help improve function of the your orthotics and avoid any potential fitting issues. Use shoes with: Orthotic-friendly shoe design has come a long way in the last few years. You don’t have to worry about wearing clunky, ugly shoes like in the past. *Shoes from Bared Footwear In 2001, a seven-year-old girl was brought by her parents into a podiatry clinic for severe flatfoot deformity. The patient was having difficulty walking long distances or standing on her feet for prolonged periods of time. She was assessed by a podiatrist and recommended custom orthotics. She was treated with medial heel skive orthoses. The patient became asymptomatic within a month of receiving treatment with significant minimised pain in her feet. In 2018, age 24, she returned to the clinic she attended in 2001 for a new pair of custom orthotics. She was still wearing the old orthotics she wore in 2001. She still had flat feet but was asymptomatic as long as she wore her custom orthotics. In conclusion, custom orthotics are an effective treatment for symptomatic flat feet. Through the use of durable materials, they last a long time. -Copyright Dr. Kevin Kirby, DPM Custom orthotics are handmade and take some time to make due to different stages to the manufacture. Also, the materials used to make them are specialised and therefore costly. At The Foot Hub, we try to make all our services affordable without compromising on quality. Make sure to take advantage of your private health insurance and our offers like Afterpay. It takes two weeks to get your orthotics to you. Should there be delays, your podiatrist will advise you at time of your appointment. The Foot Hub uses a state-of-the-art orthotic laboratory in Queensland. All orthotics are handmade with high-quality control and finishes to make sure they’re perfect for the patients. Yes, they do wear out over time due to use and activity. If the top cover of the orthotic is worn this can be easily replaced, however if the shell of the orthotic is cracked or warped, a replacement orthotic would be indicated. Depending on how often you wear them, and the materials used in custom orthotics can last for more than three years. No. Make sure to take advantage of your private health insurance and other offers like Afterpay. Orthotics can last for a long considerable amount of time. Depending on how often you wear them, and type of activity you should expect your orthotics to last over three years. Sometimes the top cover can wear out, this may need to be replaced before that. Always talk to your Podiatrist about what activity you would need your orthotics for so that suitable and durable materials can be chosen.

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Big Toe Arthiritis What is a hallux rigidus? Hallux rigidus is arthritis (wear and tear) of the joint of the big toe. It causes a destruction of the normal working of the big toe joint. The term ‘hallux’ means the big toe and ‘rigidus’ means stiffness. What causes hallux rigidus? There has been no definite cause found for hallux rigidus. The big toe takes an enormous amount of pressure during normal gait. Almost twice the amount of body weight passes through the big toe during each step which may cause wear and tear of the joint. People with flat feet may be predisposed to this condition due to the abnormal forces passing through this joint when the arch of the foot collapses. What are the symptoms caused by hallux rigidus? In the early stages you may experience Pain and stiffness of the big toe Swelling and redness around the big toe joint Pain or stiffness may worsen in cold or damp weather As it progresses you may develop Pain at rest A bony bump ‘osteophyte’ over the top of the big toe which may rub against the shoe. How is this condition diagnosed? Your consultant will examine your foot clinically and this usually makes the diagnosis clear. Particularly pain on attempts to move the big toe joint with reduced range of movement. X-rays of the foot are also taken to determine how severe the condition is. Can the condition worsen? Big toe arthritis may gradually deteriorate over several years. Initially you may experience just stiffness of the big toe but with time pain may also develop particularly on running or walking. As the condition deteriorates one may also get pain at rest. What treatment options are there? Foot wear modification Pain often occurs when the big toe bends upwards during walking.The thinner the sole of the shoe, and the higher the heel, the worse are going to be the symptoms from this condition. Therefore a shoe with a well supported stiff sole, will help reduce the amount of movement of the big toe during walking and help with your symptoms. A ‘rocker-bottom’ shoe may also help as it allows the big toe to rock forward rather than bend during gait. A ‘large toe box’ shoe is preferred to a narrow pointy toe shoe . Non steroidal anti- inflammatories A large number of patients will have good control of symptoms with non steroidal anti inflammatory medicines and may not require anything further. Several surgical options are available and your consultant will tailor based on your symptoms and degree of arthritis. ‘Cheilectomy’ involves removing the bony bump at the top of the big toe which usually causes irritation whilst wearing shoes. The big toe joint may either be fused or replaced. Fusion creates a stiff big toe which will be done with a small plate and screws. This eliminates the pain in the big toe but sacrifices movement. This is ideal for young active patients. A joint replacement on the other hand will help preserve movement but the results of a replacement are not as predictable as a fusion. A fusion remains the gold standard treatment for big toe arthritis. Is surgery necessary? The decision to proceed with surgery should be taken after non surgical options described above have been exhausted. The majority of patients will benefit from shoe wear modifications and simple painkillers. If symptoms continue to affect lifestyle and function in spite of this then surgery may be discussed with your consultant.

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Arthritis is the most common form of arthritis, and it affects people of all ages. The cause of arthritis in the feet and ankles is not entirely known, but it can be caused by anything that causes inflammation. The inflammation leads to swelling (or fluid retention) which leads to the stiffness and pain that are associated with arthritis. There are many different types of arthritis, which can be categorized as either rheumatoid, osteoarthritis, or gout depending on the symptoms. Some other causes include injury to joints; infection; viral disease; autoimmune disorders (such as lupus); metabolic disorders (such as diabetes); inflammatory bowel diseases (such as Crohn’s Disease); or any condition that may cause inflammation. Here are some ways you might experience pain from your feet or ankles. Table of Contents Arthritis in the Feet and Ankles As anyone who has ever had the condition knows, arthritis in your feet or ankles can be a painful inconvenience. There are many causes of arthritis that lead to swelling, stiffness, and pain in the joints of the feet and ankles. One common cause is inflammation due to injuries, infections, autoimmune diseases, metabolic disorders, inflammatory bowel diseases, or any other condition that causes inflammation. There are many ways you might experience pain from your feet or ankles. Some people feel shooting pains in their foot when they walk. Others may have pain when they stand for long periods of time on hard surfaces. Others may have swelling after sitting with their foot in an elevated position for too long. These are just some of the symptoms that may accompany arthritis in the feet and ankles. The most common symptom is pain in either one or both feet or ankles which can be felt while standing up straight or when walking around on flat surfaces for extended periods of time. That being said, arthritis can also show itself during times where there is prolonged pressure on the affected area such as when sitting with your foot raised up for an extended period of time or when lying down at night with your ankle propped up on a pillow. Main Causes of Arthritis The main cause of arthritis in the feet and ankles is not entirely known, but it can be caused by anything that causes inflammation. The inflammation leads to swelling (or fluid retention) which leads to the stiffness and pain that are associated with arthritis. When it comes to this type of arthritis, there are many different types, which can be categorized as either rheumatoid, osteoarthritis, or gout depending on the symptoms. Some other causes include injury to joints, infection, viral disease, autoimmune disorders (such as lupus), metabolic disorders (such as diabetes), inflammatory bowel diseases (such as Crohn’s Disease), or any condition that may cause inflammation. Here are some ways you might experience pain from your feet or ankles: 1). Sharp Pain in the Sole of Foot 2). Difficulty Wearing Shoes 3). Burning Sensation when Walking 4). Numbness in Foot 5). Hardened Joints 6) Swollen Heels Symptoms of Foot and Ankle Arthritis The symptoms of foot and ankle arthritis are pain or stiffness in the feet or ankles. Other symptoms may include swelling, which is often worse in the morning; loss of function, which could be obvious if you have to walk differently or wear shoes with a heel to avoid pain; or deformity. What Causes Arthritis? Arthritis is inflammation of the joints. The cause of this inflammation can be many different things, including injury, infection, autoimmune disorders, metabolic disorders, inflammatory bowel diseases, or any condition that may cause inflammation. Treatment for Foot and Ankle Arthritis If you’re experiencing a lot of pain from your feet or ankles, it’s important to see a doctor who specializes in arthritis. The doctor will be able to determine the cause of your foot or ankle pain. Treatment for foot and ankle arthritis includes medication, rest, and physical therapy. In some cases, surgery may be necessary as well as joint replacement surgery if the arthritis is severe enough. Prevention for Foot and Ankle Arthritis There are many ways to prevent arthritis in the feet and ankles. One of the most important things you can do is to keep your weight under control because being overweight or obese increases your risk for developing arthritis. Maintaining a healthy diet also helps, as well as ensuring that you are getting enough physical activity. There are many different activities that you can participate in, including walking, biking, swimming, gardening, dancing, stretching, or anything else that gets your blood flowing. You should also be sure to avoid any injury to your joints by using protection when participating in sports or other high impact exercises. What Causes Arthritis in the Feet? The causes of arthritis in the feet and ankles are often unknown, but the most common reason is inflammation. Inflammation is when your immune system reacts to a substance or injury and releases pro-inflammatory chemicals which can cause pain, swelling, and stiffness. This is what happens when you have arthritis, whether it’s rheumatoid, osteoarthritis, or gout. Some other causes for arthritis in the feet might include: Injury to joints Autoimmune disorder such as lupus Metabolic disorders such as diabetes Inflammatory bowel diseases like Crohn’s disease Condition that may cause inflammation (such as cancer) Is walking good for arthritis in the feet? Some people with arthritis in the feet or ankles may feel better when they walk, but this doesn’t work for everyone. You may want to consult your doctor before starting a walking program if you’re not sure what’s best for you. Many people with arthritis in the feet and ankles find that it hurts to walk because of the pain and swelling in their joints. It’s important to take breaks while you walk so that your muscles don’t get too tired and sore. The more you practice walking, the easier it will be on your body and joints. Walking can also help strengthen your muscles and keep them healthy. It can be difficult to walk when you have arthritis because of stiff joints, but there are plenty of ways to make it easier on yourself. For example, try using a cane or a walking stick for extra support when you need it. You should also wear shoes that provide good arch support and shock absorption for comfort. Weight loss is another way to help relieve some of the pressure from your joints, which will make it easier to walk around. Can you reverse arthritis in your feet? It is not possible to reverse arthritis in your feet. However, there are some lifestyle modifications that can be made to help ease the pain and discomfort associated with arthritis. Some of these modifications include: incorporating exercises into your routine; losing weight; eating a balanced diet; getting enough sleep; giving up smoking; addressing any joint injuries or infections; and maintaining an appropriate level of physical activity (such as walking). How does foot arthritis start? Foot and ankle arthritis can be caused by anything that causes inflammation, such as injury to joints or infection. Foot and ankle arthritis is often related to lifestyle factors such as obesity, smoking, and inactivity. Other causes of foot and ankle arthritis include: -Injury to the joints: This type of foot and ankle arthritis is caused by an injury to the joint in the area. This may result from a sprain or other injury that has damaged the ligaments in the area. -Infection: An infection might lead to inflammation in the joints, leading to this type of foot and ankle arthritis. You might have an infection if you have a wound that doesn’t heal properly even after one month of antibiotic treatment. -Viral disease: Viral diseases can affect your immune system, which can lead to inflammation over time. Viruses may be transferred from animals or through human contact with places where animals walk (such as a barn). Diseases like HIV can also cause this type of inflammation. -Autoimmune disorders: Disorders like lupus can cause this type of arthritis due to their autoimmune response damaging cells instead of attacking bacteria or other foreign invaders. -Metabolic disorders: Diabetes or other conditions that cause high blood sugar levels will lead to this type of foot and ankle arthritis because it results in chronic inflammation throughout the body. -Inflammatory bowel diseases: Inflammatory bowel diseases such as Crohn’s Disease will sometimes lead to this type What’s the best way to deal with arthritic feet? Choosing the right footwear can be difficult when it comes to walking and standing. But if you have arthritic feet, walking and standing in shoes might not be an option. So what do you do? The most important thing is to change your footwear and clothing depending on the weather outside. This includes switching between sandals and closed-toe shoes depending on the temperature, or wearing wide socks when it’s cold.

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Broken foot facts - The bones in the foot may be broken in many ways including direct blows, crush injuries, falls and overuse or stress. - Initial treatment may include RICE (rest, ice, compression, elevation). Rest may include the use of crutches to limit weight bearing. - X-rays often help make the diagnosis but bone scan or computerized tomography (CT scan) may be needed to help visualize the injury. - Treatment of foot fractures depend upon which bone is broken but many fractures are treated with a compression dressing, a stiff- soled shoe, and weight bearing as tolerated. - Some foot fractures require surgery to repair the damage. - Complications of foot fractures include non-union at the fracture site, arthritis if a joint is involved, and infection if the skin is broken. What is the structure of the foot? The foot is designed to withstand the considerable forces placed on it by walking, running, and jumping. There are 26 bones of the foot, connected by joints and supported by thickened ligaments to absorb the impact of movement. As well, the joints of the foot are acted upon by muscles and tendons that allow flexing and extending to permit walking and running to occur. The bony anatomy can be described as follows: - The talus articulates with the tibia (shin bone) to form the ankle joint. - The calcaneus or the heel bone is attached by ligaments to the tibia to provide stability to the ankle joint. - The midfoot consists of the navicular, the cuboid, and the three cuneiform bones. The midfoot is where inversion and supination of the foot occurs. These motions allow the sole of the foot to turn inwards and upwards. - The five metatarsal bones are connected to each toe. - The toe bones are called phalanges (single = phalanx) with the great toe having two and the other four toes having three each. These bones are named based upon their relationship to the body: proximal, middle and distal. Proximal means closest to the center of the body while distal is furthest from the center. - The arch of the foot is maintained by the plantar fascia, a thick fibrous band of tissue that runs from the calcaneus to the metatarsal, preventing the bones of the foot from flattening. - There are places in the foot where two bones meet to form a joint. Each joint has its own set of structures that help maintain stability. - Injuries to the foot include fractures of the bone, sprains of the ligaments that stabilize the joints, and strains of the muscles and tendons that move the foot. Joints can also become inflammed, which causes arthritis.

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No one intends to become a podiatric surgeon. Most readers of this information will eventually reach that position. It’s because 75% will experience significant foot problems in their lifetime. For serious foot problems, a podiatrist is your best option. A podiatrist, a doctor of podiatric medical (DPM), is a surgeon and physician who specializes on the treatment of the foot and ankle. The training of podiatrists can be very similar to that of orthopedist surgeons and other physicians. Four years of podiatric training are required in a podiatric school. Then, three years of residency training is required. Many podiatrists complete https://www.bondipodiatry.com.au/medipedi-pamper-pack a fellowship training program following their residency. After completing advanced training and clinical experience, podiatrists can be certified by a governing medical body. American Board of Foot and Ankle Surgery and American Board of Podiatric Medicine, are the two certifying boards in podiatry. Your feet are complex anatomical structures. Together, they have 52 bones. It’s about one quarter of all bones in the body. Your feet are simultaneously shock absorbers and propellers. Your ankles act as strong, stable hinges. They allow for bending and twisting in all directions, sometimes simultaneously. Your ankles need to support 1500% of your body weight when walking and 800% when running. A team of specialists can provide expert care for your feet, ankles, and legs. They have all been trained and experienced in treating patients with conditions that affect feet, ankles, and knees. DPM means that you will receive the unique expertise of a doctor to treat your foot and ankle problems. Warmer weather means the traditional Australian shoe strike, and the customary sandal-only days. Even though you want to trade your enclosed shoes for cool sandals, it is worth thinking about your soon-to-be stressed feet. While it is recommended that you clean your feet by your podiatrists, supportive shoes are still needed for everyday function. For the majority of your day, it is best to keep your supportive shoes on. You may feel the need for sandals to keep your feet cool. If this is the case, limit your use of sandals to a few hours at a time. A sandal with a thick, arched sole will give you better support than sandals or thongs that are flat and thin. The combination of summer heat and enclosed shoes can result in sweaty feet. In these conditions, microorganisms such a bacteria and fungus can thrive. It is therefore vital to practice good foot hygiene to avoid problems like onychomycosis (nail-fungus) and athlete’s foot (Tinea). Fungal skin conditions can often be misinterpreted as dry, cracked and itchy skin. On the other hand, fungal nail infection can cause white superficial spots, deep yellow patches, or soft chalky stains. Although there are many treatments, the key to restoring your skin and nail health is early diagnosis and prompt treatment. To get expert advice about diagnosis and treatment, you should contact your podiatrist right away.

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Reset Your Step By Dr. Hilary Kwan, Chiropractor Now that all the marathons, competitions, personal bests, and goals have been completed, are you left wondering if penguins were the only ones who could have happy feet? All the walking, running, and exercise we did during the summer may have come with a side order of low back, knee, and feet pain. If eyes are the windows to our soul, feet are the foundation of the whole body. And your feet have a very important job – to support the weight of our bodies. Similar to sloping, cracks, and separations in the foundation of our homes, our feet may be unstable. This can result from improper foot alignment caused by fallen arches for people with flat feet, high arches, or previous injuries like sprains and strains. Not only does improper foot alignment lead to a wide variety of foot problems, it also affects pelvis alignment that can result in back pain. The good news is you can do something about it! Orthotics can improve our stability and posture by realigning our feet and lower limbs to reduce stress and strains on the feet, knees, and low back. Not only can orthotics improve our performance during exercise, they can also prevent new and repeat ankle sprains. And perhaps most importantly, because we’re all built differently, custom-made orthotics ensure each person finds the tailored support and treatment they need. If you deal with any of the following common conditions, it’s time to consider orthotics. - Plantar Fasciitis - Heel Spurs - Bunions and Neuromas - Achilles Tendinopathy - Shin Splints - Runner’s Knee - Iliotibial Band Syndrome - Low Back Pain - Hip Pain - Sacroilliac (SI) Joint pain And perhaps the best news of all? Most extended health insurance plans cover custom orthotics; so let insurance foot this bill! Treat your feet! This September, get a $20 gift certificate when you buy a pair of custom orthotics. Book your visit.

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Arthritis develops when one or more joints become inflamed. When this occurs, it’s very likely for you to develop pain and stiffness in the affected area. Arthritis is typically common in the small joints of the foot as well as the ankle. It’s very possible that arthritis can develop due to previous injuries or traumas from the past. Some of the most common causes for arthritis may include old age, obesity, and genetic factors. It’s also been found that women who wear tight, high-heeled shoes for most of their lives are prone to experiencing foot complications such as arthritis. Some signs that point to the development of arthritis include foot pain, stiffness in the joints, swelling, clicking or popping noises, as well as difficulty walking. Since arthritis can cause so much discomfort, it’s important to look into treatment methods that can help alleviate arthritic pain. One step you can take is to invest in comfortable footwear that provides you with optimal support. Shoes with arch support, heel cups, cushioning, and shock absorption are likely to provide you with ultimate comfort while you perform your day to day activities. Your doctor may also advise you to set a weight loss goal if you happen to be obese. Losing weight may help you lessen the pressure that’s being put on your feet. Heat and ice treatments have also been found to help with easing stiffness in the joints. For more information about the type of arthritis you’re experiencing and how to best treat it, we recommend you consult with a podiatrist for professional care.

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Fractures of the bones are classified in a number of ways. A simple fracture involves a single fracture line through a bone. A comminuted fracture is one in which the bone has been fractured into two or more fragments. An open fracture is one in which the fractured bone penetrates the skin. Review Date 2/26/2020 Updated by: C. Benjamin Ma, MD, Professor, Chief, Sports Medicine and Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, CA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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Horses and humans have a few things in common. We’re both mammals, we both love to eat oats (although we favor oats in cookie format while horses seem to like the grain in a rather less embellished form) and we’re both very, very stubborn. However, humans don’t really much care for grass as a food staple, and we have no tails to speak of. Also, we walk rather differently than horses. While they put weight entirely on their toes (the hoof is essentially one big toe), human feet are designed rather differently. So, when our feet start behaving in a more equine way, it can start causing serious problems. Equinus may occur in one or both feet, and is a condition in which the ankle doesn’t bend upward properly. The normal range of motion for ankles is to lift about 10 degrees upward when you’re standing on a flat surface (i.e. when your feet are at a 90 degree angle to your leg). If you’ve got equinus, you may not be able to lift your ankle up that much, or at all. In very severe cases, your foot may even pull downward, making it difficult or even impossible for you to stand with your foot perpendicular to your leg. Equinus may be caused by several different things, although the causes may be grouped into two categories: soft tissue or bone problems. Soft tissue problems usually center around tightness in the muscles and tendons that pull the foot downward: the calf muscles and Achilles tendon. Basically, these muscles may pull the foot back and downward (toward the heel) so strongly that they overcome the strength of the muscles pulling the foot back up. These tight muscles, tendons or ligaments may simply be congenital (present at birth), inherited (part of natural genetic variation), a symptom of a neurological disorder (like cerebral palsy) or may be a result of some external cause. Injuries (or surgery) may lead to scarring, which can tighten the tissue. Or, calves may tighten when they’re in a contracted position for a long time, such as when you wear high heels all day long (you know-those times when you really wish you’d brought those old, comfortable sneakers to work), or if you wear a cast that points your toe downward. The causes aren’t always due to tight tissue, though. Sometimes there are bones blocking the ankle that keep it from moving upward fully. This may be due to a bone fragment blocking the joint (generally a result of trauma), or bones may become deformed by arthritis or tumor growth. People with equinus are likely to have problems lifting up one or both feet (they may find it either difficult or impossible to do so). In severe cases, the foot may be permanently bent downward (toward the heel). This condition may sound kind of obvious, but people may be unaware that they have equinus. Milder forms of the condition may simply cause people to adjust their gait (usually they raise the heel up earlier than normal in the walking process, might make their arches flatter, walk on their toes, or change the way their hips or knees move) in order to make up for their inability to properly lift their foot. Because this changes where stress occurs on the foot (often the ball of the foot is hit the hardest), it can lead to a whole host of other problems. For instance, if you develop equinus, you may begin to experience pain in the heel or arch (also called plantar fasciitis), painful ankles, an inflamed Achilles tendon (tendonitis), problems like calluses or even ulcers on the ball of your foot (particularly if you have diabetes), arthritis in the middle of your foot, or deformities such as bunions or hammertoes. There may also be problems further up your leg: you may experience shin splints, or cramps in your calves. Despite the name of this condition, it’s totally unnecessary to see a veterinarian when you develop equinus. Your podiatrist, while probably not intimately familiar with horse feet, has plenty of experience dealing with the human variety, and is well trained in diagnosing such conditions. When you go in to see the podiatrist, he or she will likely see how far you can move your foot up and down, both while your knee is bent and while it’s straight. (This helps to determine where the problem lies: bone, muscle, or tendon.) The podiatrist may push slightly against your foot as you try to move it (but never fear-podiatrists don’t do such things to make the examination more difficult for you-this method helps to determine the true strength of the muscles). You may also need to undergo some X-rays or other imaging process so that your podiatrist can fully understand what’s happening inside your foot. If he or she suspects your equinus may be due to an underlying neurological condition, you may be referred to a specialist for a neurological examination. Once you’ve been evaluated, your podiatrist can discuss what’s caused your particular brand of equinus and talk about the treatment options that are best for you. Because equinus is often caused by tight calf muscles, adopting a regimen of calf-stretching may improve your condition. You can also help relieve stress on the calf muscle by wearing a splint at night to keep the muscle in the proper position. Some shoe inserts can also provide relief. Because the Achilles tendon is likely to be under some strain, lifting up the heel somewhat may prove helpful. Heel cups may be used to accomplish this, or wearing shoes with moderate heels might work as well for you (although you’ll want to discuss proper heel height with your podiatrist). Orthotics (prescription shoe inserts) might also be useful in correcting the way your foot bears weight. If a neurological condition is at the heart of your problem, that can be addressed separately. If you come in to the office with a number of secondary symptoms (such as hammertoes, tendon pain, bunions, etc.), your podiatrist may treat these as well. Common treatments include (unmedicated) pads to relieve pressure (in the case of calluses), medications or treatments to reduce inflammation, and so on. Surgery may be necessary if you’re still finding yourself with a foot that behaves more like a horse’s than a human’s, even after more conservative treatment. Surgery may be used to lengthen tight muscles or tendons, or may be the best way to remove a blockage of bone, if that’s the cause of your equinus. Whatever the treatment method, your podiatrist can discuss the options with you to get your foot to act fully human again.

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