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Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry Into Cells. Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.

Lyophilization monophase solution technique for preparation of amorphous flutamide dispersions. Flutamide (FLT) is a poorly soluble anticancer drug. Therefore, lyophilized dispersions (LDs) of FLT with polyvinylpyrrolidone (PVP) K30, polyethylene glycol (PEG) 6000, and pluronic F127 were prepared via lyophilization monophase solution technique with the aim of increasing its dissolution rate. FLT showed an A(L)-type phase solubility diagrams with PVP and PEG, whereas A(N)-type diagram was obtained with pluronic. The amount of residual tertiary butyl alcohol, determined by gas chromatography, was 0.015-0.021% w/w. Differential scanning calorimetry and X-ray diffractometry revealed that FLT-polymer 1:1 LDs were partially amorphous, whereas the 1:3 and 1:5 LDs were completely amorphous. After 6 months storage, polymers under study inhibited FLT recrystallization maintaining its amorphous form. The particle size of FLT-polymer LDs was between 0.81 and 2.13 μm, with a high surface area (268.43-510.82 m²/g) and porosity (354.01-676.23 e⁻³ mL/g). Also, the poor flow properties of FLT could be improved but to a limited extent. FLT dissolution was significantly enhanced with the fastest dissolution that was achieved using pluronic. After 30 min, about 66.52%, 78.23%, and 81.64% of FLT was dissolved from 1:5 FLT-PVP, PEG, and pluronic LDs, respectively, compared with only 13.45% of FLT. These data suggest that these polymers might be useful adjuncts in preparation and stabilization of amorphous immediate-release FLT LDs.

Onercept for moderate-to-severe Crohn's disease: a randomized, double-blind, placebo-controlled trial. Onercept is a recombinant, soluble human p55 receptor to tumor necrosis factor-alpha. A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of onercept induction therapy in patients with Crohn's disease (CD). Patients (n = 207) with moderate-to-severe acute or chronic active CD were randomized to receive subcutaneous onercept (10, 25, 35, or 50 mg) or placebo 3 times weekly for 8 weeks. Primary analysis was induction of remission (defined as a CD activity index score < or = 150) at week 8. A total of 104 patients had acute active CD. Remission rates at week 8 were 23.5% for placebo (n = 17), and 34.8%, 20.0%, 26.1%, and 28.6% for onercept 10 mg (n = 23), 25 mg (n = 20), 35 mg (n = 23), and 50 mg (n = 21), respectively (P = .98). A total of 103 patients had chronic active CD. Remission rates at week 8 were 23.8% for placebo (n = 21), and 23.8%, 9.1%, 35.3%, and 13.6% for onercept 10 mg (n = 21), 25 mg (n = 22), 35 mg (n = 17), and 50 mg (n = 22), respectively (P = .66). There were no differences between treatment groups in the incidence of adverse events. However, mild-to-moderate injection-site reactions occurred in up to 12% of onercept-treated patients. Onercept was well tolerated but was not effective at the doses studied in patients with active CD.

Evaluation of the quality of oral health care in Primary Health Care in Pernambuco, Brazil, 2014. to evaluate the quality of oral health care in Primary Health Care services in Pernambuco state, Brazil, 2014. this was an ecological health evaluation study based on the Donabedian model, involving secondary data from the 2nd cycle of the National Program for Improving Access and Quality of Primary Health Care (PMAQ-AB); comparison between the structure, process and outcome variables was done using the Kruskal-Wallis test (p<0.050); variables showing statistical significance (p<0.05) were portrayed through thematic and spatial dependence maps. Results: the standard of quality in the municipalities for the 'Structure' dimension gained better scores than the 'Work process' dimension; correlations were identified between the indicators for dental urgency, supervised tooth brushing coverage and treatments completed, in quality strata related to the work process of the Oral Health teams. organization of the work process was seen to be a determining factor in the impact on some indicators of service use.

Sequence confirmation of modified oligonucleotides using IRMPD in the external ion reservoir of an electrospray ionization Fourier transform ion cyclotron mass spectrometer. Modified oligonucleotides continue to play an important role as antisense compounds that inhibit the expression of genes associated with metabolic disorders, cancer, and infectious diseases. Because the majority of modifications render these molecules refractory to standard enzymatic sequencing techniques, alternative sequencing methods which are fast and reliable are needed. In this work we explore how sugar and backbone modifications affect fragmentation patterns observed from oligonucleotides which are fragmented by infrared multiple photon dissociation in the external reservoir of an electrospray ionization Fourier transform ion cyclotron mass spectrometer. The modifications influence which fragment types (i.e., a(n)-B versus c(n)) dominate and the ease with which the oligonucleotides are fragmented. General observations for confirming the sequence of oligonucleotides are described.

A rapid liquid chromatography-tandem mass spectrometry for the quantification of Fosfomycin in plasma, urine, and aqueous fluids. A simple and fast ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the analysis of Fosfomycin in different matrices (human plasma/urine, and aqueous fluid) has been established and validated. Sample cleanup consists, depending on the matrix used, on protein precipitation or dilution with methanol containing isotopically labeled Fosfomycin as internal standard. Compounds, separated on a Luna Omega PS C18 column, were detected in multiple reactions monitoring in negative ion mode using API4000 system. With a total run time of 2min and using low volume of samples (plasma: 10μl, urine: 2μl, and aqueous fluid: 5μl), the covered ranges were: plasma (12.5-800μg/mL), urine (62.5-4000μg/mL), and aqueous fluid (1-160μg/mL). The method proved to be precise and accurate. The inaccuracy and imprecision in each matrix at the four tested quality controls including the lower limit of quantification were:: plasma (≤ 6.5%, ≤ 8%), urine (≤ 5.8%, ≤ 6.3%), and aqueous fluid (≤ 10.6%, ≤12%). The method is fast and robust which makes it relevant for pharmacokinetic studies and therapeutic drug monitoring. The appropriateness of the developed method in clinical application is also confirmed.

Hypercoagulopathy after repeated injection of 5% ethanolamine oleate to sclerose esophageal varices. Hematological and coagulating parameters were examined in 53 patients in an attempt to find possible evidence of disseminated intravascular coagulation after intravascular injection of 5% ethanolamine oleate to sclerose esophageal varices. FDP-E in the peripheral blood measured by latex photometric immunoassay significantly increased from 111.2 +/- 112.9 to 234.2 +/- 178.3 ng/ml and 370.4 +/- 189.5 ng/ml one hour after the first and second sessions of sclerotherapy, respectively (p less than 0.01). The other parameters showed no significant change, except on the first day after sclerotherapy. The increase of FDP-E was closely related to fibrinopeptide A (r = 0.689, p less than 0.01) and fibrinogen (r = 0.585, p less than 0.05), before the sclerotherapy. As repeated intravariceal sclerotherapy over short time intervals can lead to a deterioration of the coagulating system, especially in patients with abnormal preoperative coagulopathy, latex photometric immunoassay for FDP-E is a rapid and useful method of monitoring alterations in the coagulating system.

Effect of the phytotherapeutic agent eviprostat on the bladder in a rat model of bladder overdistension/emptying. Ischemia-reperfusion injury is an important factor in the development of lower urinary tract symptoms (LUTS) that is partly mediated by the generation of free radicals. We investigate the effect of the phytotherapeutic agent Eviprostat, a treatment for benign prostatic hyperplasia (BPH) that has antioxidant and anti-inflammatory activity, on urinary bladder blood flow (BBF), and function in a rat model of bladder overdistension and emptying (OE). For 8 days before surgery, OE rats received daily oral Eviprostat (36 mg/kg/day) or vehicle, while sham-operated animals received vehicle. The bladder was distended by infusion of saline over a period of 2 hr (overdistension) and then emptied. After 24 hr, BBF was measured with a laser speckle blood flow imager. The oxidative-stress marker malondialdehyde (MDA), proinflammatory cytokines, and myeloperoxidase were determined in the isolated bladder, and histological analysis was performed. Functional contractile responses of bladder strips to electrical field stimulation, carbachol, and KCl were measured. Twenty-four hours after bladder OE, a significant decrease in BBF and significant increases in bladder weight, malondialdehyde, proinflammatory cytokines, and myeloperoxidase were observed. Eviprostat almost completely prevented these changes. Histological analysis of the bladder of OE rats showed hemorrhage, accumulation of leukocytes, desquamation of epithelium, and edema, and Eviprostat suppressed these changes. The reduction in functional contractile forces in the bladder of OE rats was also prevented by Eviprostat. Eviprostat-mediated suppression of increased bladder oxidative stress and inflammation caused by bladder OE may contribute to the improvement of BBF and bladder function by Eviprostat.

Effects of stimulation of acupuncture loci Ta-Chuei (Go-14), Nei-Kuan (EH-6) and Tsu-San-Li (St-36) on thermoregulatory function of normal adults. The effects of acupuncture stimulation on the Ta-Chuei (Go-14), Nei-Kuan (EH-6), and Tsu-San-Li (St-36) loci on thermoregulatory function were assessed in normal adults. Stimulation of acupuncture locus Ta-Chuei produced hypothermia. The hypothermia was brought about by a decrease in metabolic rate, an increase in cutaneous circulation (the back region) and perspiration. On the other hand, acupuncture stimulation of either the Nei-Kuan or Tsu-San-Li loci produced a slight hyperthermia. The hyperthermia was due to a decrease in cutaneous circulation. The data indicate that each acupuncture locus may have its own function with special reference to body temperature regulation.

In-vitro bactericidal activity of cefpirome and cefamandole in combination with glycopeptides against methicillin-resistant Staphylococcus aureus. The bactericidal activity in vitro of cefpirome plus either vancomycin or teicoplanin was compared with that of a cefamandole-vancomycin combination against ten clinical isolates of homogeneous methicillin-resistant Staphylococcus aureus. Cefpirome (0.125 x MIC) combined with vancomycin (0.5-2 x MIC) or teicoplanin (0.5-4 x MIC) acted synergically against the ten isolates. Similar effects were observed with the cefamandole-vancomycin combination, except that for one isolate, higher cefamandole concentrations (0.25-1 x MIC) were required.

Scrape cytology of myositis ossificans: report of a case and analysis of the cytologic findings described previously. Myositis ossificans is a reactive, ossifying process within soft tissues, which by its clinical and histological features is considered a pseudosarcomatous lesion. There are few reports that describe the cytologic findings in myositis ossificans, and each of these mentions different cellular composition. We describe the cytology of a case of myositis ossificans in a 14-year-old boy with clinical diagnosis of soft tissue sarcoma, and analyze the most common cytologic findings reported previously of this entity. We conclude that the different cellular composition reported, reflects the different histologic components of this lesion according to the area (zonation phenomenon), and that clinico-radiologic correlation is essential for the cytological diagnosis.

Sirolimus used during pregnancy in a living related renal transplant recipient: a case report. The majority of pregnancies after transplantation reported in the literature occurred in patients treated with a combination of calcineurin inhibitors, prednisolone, and azathioprine. There is little experience with newer drugs. We report a successful pregnancy in a kidney recipient with exposure to sirolimus-based immunosuppression. We describe a case of successful delivery in a 30-year-old woman who became pregnant 1 year and 8 months after a living related renal transplantation. She received sirolimus, cyclosporine, and prednisolone before conception and during the first and second trimesters of gestation. The female recipient received sirolimus in combination with cyclosporine and prednisolone. During follow-up, her serum creatinine values were stable with pregnancy occurring at 1 year and 8 months after transplantation. At 27 gestational weeks, sirolimus was discontinued and she was maintained on cyclosporine and prednisolone. There were no signs or symptoms of graft rejection. A Cesarean section was performed at 39 weeks of gestation to deliver a healthy, 2994-g, Apgar 10, male infant. The renal function of the female recipient continued to be stable after delivery. To date, pregnancies in renal transplant recipients are still considered high risk. The U.S. National Transplantation Pregnancy Registry (NTPR) has reported increased rates of maternal and fetal complications. There have been no live births reported to the NTPR about female recipients exposed to sirolimus throughout gestation. We report a live birth without a structural defects with successful delivery after sirolimus use during the first and second trimesters of gestation.

Utilization Patterns of Topical Intranasal Steroid Therapy for Chronic Rhinosinusitis: A Canadian Population-Based Analysis. Practice guidelines have provided a strong recommendation for the daily use of topical intranasal steroid therapy for patients with chronic rhinosinusitis (CRS). Deficiencies in utilization of intranasal steroid therapy may represent a gap in quality of care. To evaluate the utilization patterns of topical intranasal steroid therapy for CRS in the Canadian population. Retrospective review of a Canadian population-based health care administrative database. A validated case definition for CRS was applied, and the utilization of topical intranasal steroid therapy within this cohort was quantified during the 2014-2015 fiscal year. Intranasal steroid spray for CRS. Primary outcome was the rate (per 100 patients) and quantity (per patient) of intranasal steroid spray utilization in patients with CRS. Secondary outcome was the geographic variation in the rate and quantity of intranasal steroid spray utilization for CRS. A total of 19 057 adult patients with CRS were evaluated. The overall rate of intranasal steroid spray utilization was 20.1 per 100 patients with CRS (3821 of 19 057). In the 3821 patients with CRS who used an intranasal steroid spray during 2014 to 2015, the mean quantity of utilization was 2.4 U (1 U = 1 bottle per month) per patient (9314 U divided by 3821 patients with CRS). There was large geographic variation in both the rate and quantity of intranasal steroid spray utilization (P < .001 for both comparisons). Topical intranasal steroid therapy continues to be underutilized for patients with CRS. Given the negative impact of low-quality medical care, outcomes from this study indicate a need to further evaluate factors leading to the underutilization of a recommended treatment in patients with CRS to improve overall health system performance.

Phase II study of 4'-deoxydoxorubicin in advanced colorectal cancer. Thirty-three patients with advanced colorectal cancer were entered on a phase II study of 4'-deoxydoxorubicin (esorubicin) (30-35 mg/m2 q 3 weekly). Objective response was documented in 4 of 25 previously untreated patients and in none of 8 previously treated patients. Toxicity was acceptable with grade 3 or 4 leukopenia occurring in 8 patients. Complete alopecia occurred only in 4 patients and gastro-intestinal toxicity was mild. A significant decrease (greater than 10%) of the left ventricular ejection fraction occurred in 8/23 patients who received greater than 2 courses of treatment.

Rate constants and equilibrium constants for binding of the gelsolin-actin complex to the barbed ends of actin filaments in the presence and absence of calcium. The equilibrium constant for binding of the gelsolin-actin complex to the barbed ends of actin filaments was measured by the depolymerizing effect of the gelsolin-actin complex on actin filaments. When the gelsolin-actin complex blocks monomer consumption at the lengthening barbed ends of treadmilling actin filaments, monomers continue to be produced at the shortening pointed ends until a new steady state is reached in which monomer production at the pointed ends is balanced by monomer consumption at the uncapped barbed ends. By using this effect the equilibrium constant for binding was determined to be about 1.5 X 10(10) M-1 in excess EGTA over total calcium (experimental conditions: 1 mM MgCl2, 100 mM KCl, pH 7.5, 37 degrees C). In the presence of Ca2+ the equilibrium constant was found to be in the range of or above 10(11) M-1. The rate constant of binding of the gelsolin-actin complex to the barbed ends was measured by inhibition of elongation of actin filaments. Nucleation of new filaments by the gelsolin-actin complex towards the pointed ends was prevented by keeping the monomer concentration below the critical monomer concentration of the pointed ends where the barbed ends of treadmilling actin filaments elongate and the pointed ends shorten. The gelsolin-actin complex was found to bind fourfold faster to the barbed ends in the presence of Ca2+ (10 X 10(6) M-1 s-1) than in excess EGTA (2.5 X 10(6) M-1 s-1). Dissociation of the gelsolin-actin complex from the barbed ends can be calculated to be rather slow. In excess EGTA the rate constant of dissociation is about 1.7 X 10(-4) s-1. In the presence of Ca2+ this dissociation rate constant is in the range of or below 10(-4) s-1.

[Social, economic and psychological issues as cardiovascular disease risk factors]. The highest mortality in developed countries is, according to the data from our as well as international literature, among people from low socioeconomic backgrounds. No recent data are available for the Czech Republic. We compared the estimated median life expectancy in 2001-2005 with the proportion of people with basic education only and with the proportion of unemployed in all regions within the Czech Republic. We confirmed significant negative correlation--people in regions with low socioeconomic status had lower estimated median life expectancy. Despite the decline in the total and cardiovascular mortality in particular in the Czech Republic over the last 20 years, the highest mortality and shortest medium life expectancy continue to persist in the regions with the lowest socioeconomic status as measured by the educational status and unemployment.

The effect of Dotarizine (Ca2+ channel blocker) on cerebral vessel reactivity in animals subjected to hyperventilation and anoxia. Dotarizine--a novel piperazine derivative--belongs to wide spectrum Ca+ channel antagonists. It was reported to have strong vasodilatory and antiserotoninergic activities. Unlike other Ca+ channel blockers Dotarizine was found to have lower oral toxicity. In the presented study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hyperventilation and hypoxic conditions of rabbits. In the first experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. The results revealed that oral administration of Dotarizine diminished the vasoconstrictive effect of hyperventilation and this was more pronounced in MCA than in BA. During anoxic conditions stronger vasodilatory effects were observed in both groups of vessels and the low value of pulsatility index (PI) reflected pronounced decrease of the peripheral resistance, in comparison to the control group. Thus, the oral administration of Dotarizine decreases the peripheral resistance of cerebral vessels and therefore seems to have influence on the minute arteries of cerebrovascular system of the brain.

tert-butyl hydroperoxide-dependent microsomal release of iron and lipid peroxidation. II. Evidence for the involvement of nonheme, nonferritin iron in lipid peroxidation. In a previous study tert-butyl hydroperoxide (t-BOOH) was found to promote reductive release of nonheme, nonferritin iron from rat liver microsomes. The reaction was catalyzed by cytochrome P450 and was strictly contingent on the availability of ADP. In this study, t-BOOH was also found to promote microsomal lipid peroxidation, as evidenced by formation of malondialdehyde. t-BOOH-dependent lipid peroxidation was stimulated by ADP, and four lines of evidence suggested that such stimulation was mediated by reductive release and subsequent redox cycling of nonheme, nonferritin iron. First, lipid peroxidation was stimulated by the same concentration of ADP that promoted iron release. Second, depletion of nonheme, nonferritin iron by pretreatment of rats with phenobarbital decreased the stimulation of lipid peroxidation by ADP. Third, the effect of ADP was maximal when the concentration of t-BOOH was adjusted to values that yielded maximum iron release. Fourth, the effect of ADP was abolished by bathophenanthroline, which is known to chelate ferrous iron in a redox inactive form. These results suggest that the reductive release of nonheme, nonferritin iron exacerbates the deleterious effects of t-BOOH on microsomal lipids.

Enterocolic increase of cannabinoid receptor type 1 and type 2 and clinical improvement after probiotic administration in dogs with chronic signs of colonic dysmotility without mucosal inflammatory changes. Colonic dysmotility in dogs can cause different GI signs. Sometimes, histology of enterocolic biopsies does not reveal inflammatory infiltrates or mucosal lesions that are typically associated with clinical disease activity. It is speculated that, similarly to humans, colonic dysmotility may be anxiety-based, although recent data demonstrate that irritable bowel syndrome (IBS) could result from acute infectious enteritis. Specific Lactobacillus spp. strains administered orally in humans induced the expression of μ-opioid and cannabinoid receptors in mucosal enterocytes, modulating intestinal morphine-like analgesic functions. We investigated the potential association of GI signs caused by colonic dysmotility and mucosal expression of cannabinoid receptors in intestinal epithelial cells and the number of mucosal mast cells. Ten to 15 endoscopic biopsies were collected from colonic mucosa of 20 dogs diagnosed with dysmotility disturbances before and after probiotic (Slab51 bacterial blend; Sivoy® ) administration (3-month period). Number and distribution of mast cells (MCs), and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated by immunohistochemistry and PCR. Results were compared to data obtained from five clinically healthy dogs (archive samples). Decreased numbers of MCs (P < .0001) and increased CB1- and CB2-positive epithelial cells (P < .0001) in diseased dogs were positively associated with post-treatment CCECAI scores (P < .0001). Our results suggest that probiotic administration can reduce signs of colonic dysmotility, possibly due to microbiota modulation and epithelial cell receptor-mediated signaling in intestinal mucosa.

Systematic review of outcomes of patients undergoing resection for colorectal liver metastases in the setting of extra hepatic disease. Surgical resection for patients with colorectal liver metastases (CRLM) can offer patients a significant survival benefit. We hypothesised that patients with CRLM and extra hepatic disease (EHD) undergoing metastasectomy had comparable survival and describe outcomes based on the distribution of metastatic disease. A systematic search using a predefined registered protocol was undertaken between January 2003 and June 2012. Primary exposure was hepatic resection for CRLM and primary outcome measure was overall survival. Meta-regression techniques were used to analyse differences between patients with and without extra hepatic disease. From a pool of 4996 articles, 50 were retained for data extraction (3481 CRLM patients with EHD). The median survival (MS) was 30.5 (range, 9-98) months which was achieved with an operative mortality rate of 0-4.2%. The 3-year and 5-year overall survival (OS) were 42.4% (range, 20.6-77%) and 28% (range, 0-61%) respectively. Patients with EHD of the lungs had a MS of 45 (range, 39-98) months versus lymph nodes (portal and para-aortic) 26 (range, 21-48) months versus peritoneum 29 (range, 18-32) months. The MS also varied by the amount of liver disease - 42.2months (<two lesions) versus 39.6months (two lesions) versus 28months (⩾three lesions). In the evolving landscape of multimodality therapy, selective hepatic resection for CRLM patients with EHD is feasible with potential impact on survival. Patients with minimal liver disease and EHD in the lung achieve the best outcome.

Role of CT angiography with three-dimensional reconstruction of mesenteric vessels in laparoscopic colorectal resections: a randomized controlled trial. Laparoscopic surgery, despite its well-known advantages and continuous technological innovations, still has limitations such as the lack of tactile sensation and reduced view of the operative field. These limitations are particularly evident when performing laparoscopic colorectal resection due to the variability of the number and course of mesenteric vessels. Today, the patient's vascular anatomy can be mapped using computed tomography (CT) angiography and processing of the images with rendering software to reconstruct a three-dimensional model of the mesenteric vessels. To assess how prior knowledge of the patient's mesenteric vascular anatomy represents an advantage when performing laparoscopic colorectal resections, we conducted a randomized, parallel, single-blinded controlled trial. From January 2010 to January 2012, all patients with surgical indication to undergo standardized right or left hemicolectomy and anterior rectal resections were randomly assigned to two groups and subjected to CT angiography with three-dimensional reconstruction of mesenteric vessels. In the first group the surgeon was able to view the 3D reconstruction before and during surgery, while in the second group the surgeon was only able to view the 3D reconstruction after surgery. Evaluation of data from 112 patients shows statistically significantly lower operative time, episodes of difficult identification of right anatomy, and incidence of intraoperative and postoperative complication related to difficult or erroneous identification of mesenteric vessels in the group in which the surgeon was able to view the 3D reconstruction before and during surgery compared with the control group. This study shows that prior knowledge of the patient's mesenteric vascular anatomy represents an advantage when performing laparoscopic colorectal resection.

Deregulation of energetic metabolism in the clear cell renal cell carcinoma: A multiple pathway analysis based on microarray profiling. Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. In order to better understand the biology of ccRCC, we accomplished the gene profiling of fresh tissue specimens from 11 patients with the renal tumors (9 ccRCCs, 1 oncocytoma and 1 renal B-lymphoma), in which the tumor-related data were compared to the paired healthy kidney tissues from the same patients. All ccRCCs exhibited a considerably elevated transcription of the gene coding for carbonic anhydrase IX (CAIX). Moreover, the ccRCC tumors consistently displayed increased expression of genes encoding the glycolytic pathway enzymes, e.g. hexokinase II (HK2) and lactate dehydrogenase A (LDHA) and a decreased expression of genes for the mitochondrial electron transport chain components, indicating an overall reprogramming of the energetic metabolism in this tumor type. This appears to be accompanied by altered expression of the genes of the pH regulating machinery, including ion and lactate transporters. Immunohistochemical staining of tumor tissue sections confirmed the increased expression of CAIX, HK2 and LDHA in ccRCC, validating the microarray data and supporting their potential as the energetic metabolism-related biomarkers of the ccRCC.

[Role of endogenous intoxication in multiple organ dysfunction development in cardiosurgical patients in early postoperative period]. to evaluate endogenous intoxication (EI) and multiple organ dysfunction (MOD) in cardiosurgical patients after open heart surgery. twenty six patients with MOD signs and 29 patients with an uneventful postoperative period were studied. MOD severity was assessed with SOFA scoring. EI was quantified with middle molecular weight peptides (MMWP), malondialdehyde and couple triens. on the first postoperative day MOD patients were characterized by high EI (MMWP: +36.7%), while control patients had a mild EI (MMWP: +20.7%). On the 3rd-4th postoperative days in the main group SOFA scores was decreased and EI intensity was increased (MMWP: +43.3%), while in the control group EI fitted the preoperative value. The major defference on the 10th-12th postoperative day was observed. In the main group severity of MOD matched that over the previous period. The intensity of EI remained elevated (MMWP: +30%), while in the control group EI level was equal to the baseline. The correlation analysis showed a positive relationship between EI and MOD pareameters, and positive connection between EI/MOD parameters and cardiopulmonary bypass/aortal occlusion duration. patients with MOD have more considerable EI compared with an uneventful postoperative period. EI increase is one of the main causes of MOD development in cardiac surgery patients. Cardiopulmonary bypass/aortal occlusion potentiate endogenous intoxication and MOD development after cardiac surgery.

Applying the International Classification of Functioning, Disability and Health (ICF) to measure childhood disability. The International Classification of Functioning, Disability and Health-ICF addresses the broad need for a common language and classification of functioning and disability. A parallel need is appropriate measures compatible with the content of the ICF to document the nature and impact of limitations of function, activities and participation. The interaction of developmental characteristics and disability among children represent special challenges for classification as well as measurement. Demographic trends emphasize the need for universal measures that encompass the components of the ICF and can be used in surveillance, screening and evaluation. This paper identifies issues related to application of the ICF to measure disability in childhood; reviews approaches and tools to assess childhood disability and identifies priorities for the development of measures of functioning and disability in children based on the ICF. The development of measures should be framed within a framework of children's rights and application of the biopsychosocial model to document profiles of functioning and disability of children.

Lattice boltzmann method for compressible flows with high mach numbers In this paper we present a lattice Boltzmann model to simulate compressible flows by introducing an attractive force. This scheme has two main advantages: one is to soften sound speed effectively, which greatly raises the Mach number (up to 5); another is its relative simple procedure. Simulations of the March cone and the comparison between theoretical expectations and simulations demonstrate that the scheme is effective in the simulation of compressible flows with high Mach numbers, which would create many new applications.

Safety and toxicological evaluation of a novel, fermented, peptide-enriched, hydrolyzed swine placenta extract powder. Placenta is an important organ that connects the developing fetus to allow nutrient uptake, antibody provisions and gas exchange via the blood supply of the mother. We developed a novel, standardized, stable, water-soluble, peptide-enriched hydrolyzed, Horus fermented placenta powder (HFPEP) from healthy, pathogen-free, swine placenta. Earlier studies demonstrated that HFPEP significantly improves physical fatigue, hepatic functions and repair of muscle fibers. We examined the broad safety of HFPEP in various toxicology models in Good Laboratory Practices-approved laboratories. The acute oral toxicity study was conducted in female Sprague-Dawley rats, and the acute oral LD50 was found to be greater than 5000 mg/kg body weight. Ames' bacterial reverse mutation assay was conducted to determine the ability of HFPEP to induce reverse mutation at selected histidine loci in five tester strains of Salmonella typhimurium viz. TA1535, TA1537, TA98, TA100 and TA102 in the presence and absence of a metabolic activation system (S9) at the doses of 50, 15, 4.5, 1.35 and 0.41 mg/ml. No mutagenic potential was observed. Mutagenic potential was also evaluated using in vivo micronucleus test, and no mutagenic potential of HFPEP was observed. Repeated dose 28-d oral toxicity study was performed in male and female rats with 14-d recovery period at the dose levels of 250, 500 or 1000 mg/kg. No abnormal clinical signs or toxicity were detected. No observed adverse effect level of HFPEP was found to be greater than 1000 mg/kg body weight. These studies affirm that HFPEP has broad spectrum safety for human consumption.

En bloc excision of proximal nail fold for treatment of chronic paronychia. Chronic paronychia is a very recalcitrant dermatosis, which is particularly prevalent in housewives. Medical treatment for this condition is unsatisfactory in a significant number of cases. Surgical approach forms an important part of management, however, this area has received little attention. Various surgical approaches have been tried in the past but a comparative analysis has not been attempted. The present study aims at assessing the efficacy of en bloc excision of proximal nail fold (PNF). Moreover, a comparative analysis has been undertaken to assess whether or not simultaneous nail plate avulsion improves the treatment outcome. Thirty patients of chronic paronychia with nail plate irregularities were randomly divided into two treatment groups (15 patients each). After a detailed evaluation, en bloc excision of PNF with or without nail plate removal was performed. Postoperative measures were advised and the patients were kept under regular follow-up thereafter. Assessment of postoperative complications was also performed. Twelve patients in group I and 13 patients in group II completed the treatment protocol. Of these, 70% of patients were cured in group II (en bloc excision with nail avulsion) whereas only 41% were cured in group I (en bloc excision without nail avulsion). En bloc excision of the PNF is a useful method in recalcitrant chronic paronychia. Simultaneous avulsion of the nail plate improves the surgical outcome. Strict avoidance of irritant exposure is necessary to ensure complete treatment and prevent recurrence.

Assessment of an Advanced Vision Screener in the Detection of Amblyopia in the Nebraska Pediatric Population. To determine the validity of the OPTEC 5500 vision screener (Stereo Optical Co., Inc., Chicago, IL) in assessing visual acuity and amblyopia in pediatric patients between the ages of 3 and 17 years by comparing it statistically to gold standard comprehensive ophthalmic examinations. A cross-sectional study was conducted of 64 patients between the ages of 3 and 17 years who underwent a vision screening test at a pediatric ophthalmology office using the OPTEC 5500 vision screener, followed by traditional visual acuity testing via the Snellen or Lea optotypes. After data were collected, the results of the OPTEC 5500 vision screener were compared to the Snellen and Lea visual acuity tests and statistical analysis was subsequently performed for the right and left eyes separately. Patients were considered to have risk factors for amblyopia based on the American Association for Pediatric Ophthalmology and Strabismus referral criteria guidelines. The results of the OPTEC 5500 vision screener for the right eye of participants of all ages were a sensitivity of 77.4%, specificity of 100.0%, positive predictive value of 100.0%, negative predictive value of 50.0%, and accuracy of 81.5%. Results for the left eye were a sensitivity of 81.0%, specificity of 87.0%, positive predictive value of 91.9%, negative predictive value of 71.4%, and accuracy of 83.1%. Although the specificity and positive predictive value were acceptable, the sensitivity and negative predictive value of the OPTEC 5500 vision screener were below average when compared to other available devices, exhibiting some of the weaknesses of the device. Additional studies of the OPTEC 5500 vision screener with a larger population are necessary to assess the device in the general pediatric population, such as in general pediatric clinics and public schools. Additionally, other options for pediatric vision screening devices should be explored. [J Pediatr Ophthalmol Strabismus. 2018;55(3):189-193.].

Right ventricular function in patients treated with inhaled nitric oxide after cardiac surgery for congenital heart disease in newborns and children. Measurement of right ventricular (RV) function is essential for complete assessment of the effects of inhaled nitric oxide in the postoperative cardiac patient; nitric oxide therapy can result in a decrease in pulmonary vascular resistance and improved echocardiographic RV ejection fraction without necessarily inducing a significant change in pulmonary artery pressure.

In vitro and in vivo persistence of reticulocytes from donor red cells. Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit. Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37 degrees C by using thiazole orange staining and flow cytometric analysis. Two-color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients. Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA-1 blood was temperature-dependent. Reticulocytes disappeared over 13 and 6 days at 24 degrees C and 37 degrees C, respectively, but at 4 degrees C the reticulocyte count changed little over 35 days. Two-color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients. This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure. Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.

A review of methods used for hazard identification and risk assessment of environmental hazards. Approximately one quarter of all deaths globally are attributed to living or working in an unhealthy environment, with household and ambient air pollution, along with exposures to ultraviolet radiation and chemicals amongst the leading causes. At present there are no international standards for assessing the risks of these environmental hazards. The use of heterogeneous methods to identify health risks from environmental hazards may reduce the level of confidence the public has in the conclusions that are made. To describe and compare the processes and methods used by national and international organisations that conduct hazard identification and/or risk assessment (HI/RA) of environmental hazards and to identify knowledge gaps to inform the development of future methods. We searched the websites of 19 organisations (ten national, five international and four World Health Organization (WHO) units) and extracted data from all relevant, publicly available resources which described the processes and methods used in HI/RA of environmental hazards. We contacted each organisation for any additional information. Five organisations were excluded from further analysis: three made recommendations but did not conduct HI/RA; one used heterogenous methods across their reviews for HI; and one WHO unit did not have any published guidelines. Of the 14 organisations analysed, five (36%) describe the process for establishing the questions to be answered in the assessments. Only one (7%) organisation uses systematic review methods, although five (36%) state that they use such methods. Ten (71%) assess the scientific quality of the included studies, however only three (21%) use explicit criteria. Only three (21%) organisations assess the quality of the body of evidence using explicit criteria. Four (29%) organisations describe the process for making the final HI conclusions and three (38%) the final RA conclusions. Eight (57%) have a conflict of interest policy and seven (50%) organisations describe a process for managing them. The US Office of Health Assessment and Translation and the World Health Organisation meet the most criteria for describing their processes and methods. The processes and methods used by organisations conducting HI/RA of environmental hazards are inconsistent. There is a need for empirically based tools and methods to be adopted for the evaluation and synthesis of evidence, and the formulation of conclusions across all organisations that conduct HI or RA. These tools and methods will lead to increased transparency, comparability and validity of the assessments.

Thermodynamic signatures of quantum criticality in cuprate superconductors. The three central phenomena of cuprate (copper oxide) superconductors are linked by a common doping level p*-at which the enigmatic pseudogap phase ends and the resistivity exhibits an anomalous linear dependence on temperature, and around which the superconducting phase forms a dome-shaped area in the phase diagram1. However, the fundamental nature of p* remains unclear, in particular regarding whether it marks a true quantum phase transition. Here we measure the specific heat C of the cuprates Eu-LSCO and Nd-LSCO at low temperature in magnetic fields large enough to suppress superconductivity, over a wide doping range2 that includes p*. As a function of doping, we find that Cel/T is strongly peaked at p* (where Cel is the electronic contribution to C) and exhibits a log(1/T) dependence as temperature T tends to zero. These are the classic thermodynamic signatures of a quantum critical point3-5, as observed in heavy-fermion6 and iron-based7 superconductors at the point where their antiferromagnetic phase comes to an end. We conclude that the pseudogap phase of cuprates ends at a quantum critical point, the associated fluctuations of which are probably involved in d-wave pairing and the anomalous scattering of charge carriers.

Prior task experience and comparable stimulus exposure nullify focal and nonfocal prospective memory retrieval differences. We explored the nature of focal versus nonfocal event-based prospective memory retrieval. In the context of a lexical decision task, people received an intention to respond to a single word (focal) in one condition and to a category label (nonfocal) for the other condition. Participants experienced both conditions, and their order was manipulated. The focal instruction condition was a single word presented multiple times. In Experiment 1, the stimuli in the nonfocal condition were different exemplars from a category, each presented once. In the nonfocal condition retrieval was poorer and reaction times were slower during the ongoing task as compared to the focal condition, replicating prior findings. In Experiment 2, the stimulus in the nonfocal condition was a single category exemplar repeated multiple times. When this single-exemplar nonfocal condition followed in time the single-item focal condition, focal versus nonfocal performance was virtually indistinguishable. These results demonstrate that people can modify their stimulus processing and expectations in event-based prospective memory tasks based on experience with the nature of prospective cues and with the ongoing task.

Comparative ethics and geriatric psychiatry: looking at motivations. In the broadest sense, medicine is a biologic-anthropologic model. The latest data on epidemiology and biology confirm earlier apprehensions about life expectancy, number of elderly, and the impact of mental impairment. The author wishes to reflect rather on anthropology by comparing the American and French cultures faced with the ethical dilemmas of aging and end-of-life issues. On this perilous frontier of biomedical ethics, the author suggests that the right to be treated as a person is an effective source of motivation for physicians to respect the dignity of geriatric patients in the context of high-technology medicine.

A series of template plasmids for Escherichia coli genome engineering. Metabolic engineering strategies often employ multi-copy episomal vectors to overexpress genes. However, chromosome-based overexpression is preferred as it avoids the use of selective pressure and reduces metabolic burden on the cell. We have constructed a series of template plasmids for λ Red-mediated Escherichia coli genome engineering. The template plasmids allow construction of genome integrating cassettes that can be used to integrate single copies of DNA sequences at predetermined sites or replace promoter regions. The constructed cassettes provide flexibility in terms of expression levels achieved and antibiotics used for selection, as well as allowing construction of marker-free strains. The modular design of the template plasmids allows replacement of genetic parts to construct new templates. Gene integration and promoter replacement using the template plasmids are illustrated.

Origin of high acetylcholinesterase activity in the mouse superior colliculus. The acetylcholinesterase activity in the colliculus mainly occurs in two layers and is arranged as a lattice in the intermediate grey layer and as a continuous sheet in the superficial grey layer. Undercutting lesions abolish the lattice in the intermediate grey layer but leave the superficial sheet of activity intact. By contrast the injection of kainic acid into the colliculus leaves the intermediate layer lattice intact while causing a local reduction in the superficial layer. Injections of the retrograde tracer Fluoro-Gold into the colliculus labels cells in the pedunculopontine and laterodorsal tegmental nuclei that contains acetylcholinesterase. Cells in the parabigeminal nucleus are also labelled but these cells contain low levels of cholinesterase. Thus, it is concluded that the lattice in the intermediate layers is mainly dependent on afferents from the laterodorsal tegmental and pedunculopontine nuclei while the sheet in the superficial layers is mainly dependent on intrinsic cells.

Inhibition of adenylyl cyclase isoforms V and VI by various Gbetagamma subunits. An intriguing development in the G-protein signaling field has been the finding that not only the Galpha subunit, but also Gbetagamma subunits, affect a number of downstream target molecules. One of the downstream targets of Gbetagamma is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhibited or stimulated by Gbetagamma subunits. Until now, adenylyl cyclase type I has been the only isoform reported to be inhibited by free Gbetagamma. Here we show by transient cotransfection into COS-7 cells of either adenylyl cyclase V or VI, together with Ggamma2 and various Gbeta subunits, that these two adenylyl cyclase isozymes are markedly inhibited by Gbetagamma. In addition, we show that Gbeta1 and Gbeta5 subunits differ in their activity. Gbeta1 transfected alone markedly inhibited adenylyl cylcase V and VI (probably by recruiting endogenous Ggamma subunits). On the other hand, Gbeta5 produced less inhibition of these isozymes, and its activity was enhanced by the addition of Ggamma2. These results demonstrate that adenylyl cyclase types V and VI are inhibited by Gbetagamma dimers and that Gbeta1 and Gbeta5 subunits differ in their capacity to regulate these adenylyl cyclase isozymes.

Tumor necrosis factor (TNF) stimulates the production of nerve growth factor in fibroblasts via the 55-kDa type 1 TNF receptor. The role of the two types of tumor necrosis factor (TNF) receptors, TNF-R1 and TNF-R2, in mediating the capacity of TNF to stimulate nerve growth factor (NGF) production in fibroblasts has been investigated. Although Swiss 3T3 cells express both the TNF-R1 and TNF-R2, an agonistic anti-TNF R1 antibody, but not an agonistic anti-TNF-R2 antibody, increases the NGF mRNA level and stimulates the production of NGF protein in the cells. Treatment of the cells with a combination of anti-TNF-R2 antibody and interleukin-1 beta (IL-1 beta) does not increase the NGF production induced by IL-1 beta alone, although TNF's activity to stimulate NGF production is markedly enhanced by IL-1 beta. Furthermore, simultaneous addition of the both antibodies does not increase the NGF production above that observed with the anti-TNF-R1 antibody, indicating that TNF-R1 alone mediates the TNF's activity to stimulate NGF production in fibroblasts.

Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis. Fibrosis, a cardinal feature of a dysfunctional liver, significantly contributes to the ever-increasing mortality due to end-stage chronic liver diseases. The crosstalk between hepatocytes and hepatic stellate cells (HSCs) plays a key role in the progression of fibrosis. Although ample efforts have been devoted to elucidate the functions of HSCs during liver fibrosis, the regulatory functions of hepatocytes remain elusive. Using an unbiased functional microRNA (miRNA) screening, we investigated the ability of hepatocytes to regulate fibrosis by fine-tuning gene expression via miRNA modulation. The in vivo functional analyses were performed by inhibiting miRNA in hepatocytes using adeno-associated virus in carbon-tetrachloride- and 3,5-di-diethoxycarbonyl-1,4-dihydrocollidine-induced liver fibrosis. Blocking miRNA-221-3p function in hepatocytes during chronic liver injury facilitated recovery of the liver and faster resolution of the deposited extracellular matrix. Furthermore, we demonstrate that reduced secretion of C-C motif chemokine ligand 2, as a result of post-transcriptional regulation of GNAI2 (G protein alpha inhibiting activity polypeptide 2) by miRNA-221-3p, mitigates liver fibrosis. Collectively, miRNA modulation in hepatocytes, an easy-to-target cell type in the liver, may serve as a potential therapeutic approach for liver fibrosis. Liver fibrosis majorly contributes to mortality resulting from various liver diseases. We discovered a small RNA known as miRNA-221-3p, whose downregulation in hepatocytes results in reduced liver fibrosis. Thus, inhibition of miRNA-221-3p may serve as one of the therapeutic approaches for treatment of liver fibrosis.

Korea red ginseng water extract increases nitric oxide concentrations in exhaled breath. Panax ginseng is well known to enhance the release of nitric oxide (NO) from endothelial cells of the rat aorta and to reduce blood pressure in animals. In this study, we investigated the effects of water extract of Korea red ginseng (KRG) on NO concentration levels in the exhaled breath, blood pressure, and heart rate of human volunteers. We also are interested in whether NO levels in exhaled breath are increased by KRG extract, and correlated with blood pressure and heart rate. Twelve healthy, non-smoking male volunteers were recruited for this study. A single administration of KRG water extract (500 mg/50 kg) increased NO levels in exhaled breath, and concomitantly decreased mean blood pressure and heart rate. The correlation value between NO levels and heart rate (r = 0.94), and the correlation value between NO levels and heart rate (r = 0.84) are significant (P < 0.01). Linear regression analysis shows the clear conversed correlation between NO levels and blood pressure as well as heart rate. Therefore, present data suggest that KRG may be useful for the treatment of hypertension and pulmonary vascular obstruction.

The effect of fiber orientation on the polymerization shrinkage strain of fiber-reinforced composites. The aim of this study was to characterize the linear polymerization shrinkage strain of glass fiber-reinforced composite (FRC) according to the fiber orientation. Test specimens (n=5) (10.0 x 10.0 x 1.5mm) were prepared from different brands of photopolymerizable resin-preimpregnated FRC; unidirectional continuous FRC, experimental random-oriented FRC, and bidirectional continuous FRC. As control materials, particulate filler composite resin and unfilled dimethacrylate monomer resin were used. Two uniaxial strain gages (gage length 2mm) were used to measure shrinkage strains in two directions: longitudinally and transversally to the fiber direction. The uncured composite or resin was placed on top of the strain gages, covered with a separating sheet and a glass plate, and irradiated for 40s with a light-curing unit. The shrinkage strain was monitored for 300 s. ANOVA and Tukey's posthoc test were used at a significance level of 0.05. ANOVA revealed that orientation of fiber and brand of material had a significant effect (P<0.05) on shrinkage strain. The unidirectional FRC revealed no shrinkage longitudinally to the fiber direction, whereas the shrinkage occurred transversally to the fiber direction. Particulate filler composite resin and unfilled resin revealed equal shrinkage strain in both of the measured directions. Anisotropic nature of FRC exists with regard to polymerization shrinkage strain. The variation of polymerization shrinkage strains of FRC compared to those of particulate filler composites and unfilled resin might be important for future clinical applications.

[Biochemical heterogeneity of mitochondria]. Rat liver mitochondria were fractionated on the basis of their sedimentation coefficients in the gradient of ficoll. The fractions ("heavy", "middle" and "light" mitochondria) were heterogeneous with regard to the content of protein, DNA, cytochrome a + a3 and respiratory activity. Heterogeneity of mitochondria did not result from the damage or microsomal and lysosomal contamination. The biosynthesis of DNA, RNA and proteins in the different fractions of mitochondria was studied. In vivo incorporation of radioactive precursor into RNA was highest in the fractions of "middle" mitochondria, whereas in vitro the "heavy" mitochondria showed maximum activity in the synthesis of RNA. In vitro DNA synthes was maximum in the fractions of "heavy" mitochondria, protein synthesis in "heavy" and "light" mitochondria. Activity of the synthesis of RNA, DNA and proteins in vitro depends on the content of DNA and cytochrome a + a3 in the different fractions of mitochondria. It is supposed that heterogeneity of mitochondria may be connected with their biogenesis.

Biomechanical evaluation of a novel dynamic posterior cruciate ligament brace. Use of a rigid brace or cast immobilization is recommended in conservative treatment or postoperative rehabilitation after a posterior cruciate ligament injury. To prevent the loss of knee joint function and muscle activity often associated with this, a flexible knee brace has been developed that allows an adjustable anteriorly directed force to be applied to the calf in order to prevent posterior tibial translation. The purpose of this biomechanical study was to evaluate the impact of this novel dynamic brace on posterior tibial translation after posterior cruciate ligament injury and reconstruction. A Telos stress device was used to provoke posterior tibial translation in seven human lower limb specimens, and stress radiographs were taken at 90° of knee flexion. Posterior tibial translation was measured in the native knees with an intact posterior cruciate ligament; after arthroscopic posterior cruciate ligament dissection with and without a brace; and after posterior cruciate ligament reconstruction with and without a brace. The force applied with the brace was measured using a pressure sensor. Posterior tibial translation was significantly reduced (P=0.032) after application of the brace with an anteriorly directed force of 50N to the knees with the dissected posterior cruciate ligament. The brace also significantly reduced posterior tibial translation after posterior cruciate ligament reconstruction in comparison with reconstructed knees without a brace (P=0.005). Posterior tibial translation was reduced to physiological values using this dynamic brace system that allows an anteriorly directed force to be applied to the calf.

Trigeminal autonomic cephalgia with periorbital ecchymosis, ocular hemorrhage, hypertension and behavioral alterations. We describe a 38-year-old male in whom severe unilateral headache was associated with marked palpebral edema, periorbital ecchymosis, lacrimation, conjunctival injection, nasal congestion and rhinorrhea. A second, less severe headache form developed subsequently. The patient often presented severe labile hypertension and behavioral disturbances during the crises, and there was an episode of intra-ocular hemorrhage. General, neurological and ophthalmological examinations revealed nothing remarkable. We discuss possible pathogenetic mechanisms and the nosology of this case within the trigeminal autonomic cephalgias.

Translation, cultural adaptation, and Rasch analysis of the visual function (VF-14) questionnaire. To translate, culturally adapt, and validate the original and previously validated shorter versions of the Visual Function Index (VF-14) questionnaire in a Chinese population. The VF-14 was completed by patients with cataract. The analysis was carried out in three phases: phase I, testing whether the VF-14 and its valid shorter versions,VF-8R and VF-11R, form valid scales in Chinese settings using Rasch analysis; phase II, developing completely new Chinese versions of the VF-14; phase III, testing whether the previously validated shorter versions of the VF-14 could be applied in a Chinese population. This was tested by assessing the agreement between the new Chinese (developed in phase II) and the previously validated shorter versions of the VF-14 using Bland-Altman plots. A total of 456 patients (median age, 70 years; range, 40-92 years; females, 58%) completed the Chinese translated version of the VF-14. The VF-14 and the VF-11R demonstrated good Rasch based psychometric properties when a grossly misfitting item was removed. The VF-8R formed a valid scale without any modification. The scores of the VF-11R and the Chinese shorter version (VF-11RChin) showed very good agreement, with a mean difference of -0.18 logits and 95% limits of agreement between 0.11 and -0.47. The Chinese translated VF-14, VF-11R, and VF-8R were valid and could be applied to assess cataract outcomes in Chinese settings. The existing shorter version had good agreement with the new Chinese version, which signifies that there was no need to develop a different version of the VF-14 in China.

The action of isoprenaline on the electrophysiological properties of hypertrophied left ventricular myocytes. The electrophysiological effects of the beta-agonist, isoprenaline, on hypertrophied left ventricular myocardium were measured to understand better the arrhythmic effects of beta-stimulation on the hypertrophied heart. Left ventricular hypertrophy was induced in guinea-pigs by constriction of the thoracic aorta. An age-matched sham-operated group served as controls. Isolated myocytes were held under voltage- and current clamp and the effect of isoprenaline on the L-type Ca2+ current, I(Ca), a Cl- current, I(Cl), and action potential morphology were measured. Cardiac growth was mirrored by cellular hypertrophy. I(Ca) and I(Cl) current density were reduced as myocyte hypertrophy progressed. The augmentation of I(Ca) and I(Cl) by isoprenaline was also reduced in hypertrophy, but no other characteristics of the two currents, or the dose-dependency of the action of isoprenaline were a function of cardiac growth. Isoprenaline prolonged the action potential, but to a smaller extent in hypertrophied myocytes. This difference in action potential prolongation was abolished by glibenclamide. The changes to I(Ca) and I(Cl) in hypertrophy would not tend to increase triggered activity in this situation. Under maximum inotropic stimulation hypertrophied myocytes show action potential changes which are consistent with intracellular ATP depletion, and which could enhance the likelihood of re-entrant circuits. A simple diffusion model for oxygen is constructed to demonstrate the possibility of cellular hypoxia in hypertrophied myocytes.

The surgical treatment of drooling in healthy children. Drooling is a distressing symptom. It is usually found in children suffering from cerebral palsy, but may also be encountered in healthy children. There are different known surgical methods to stop drooling. We think that the most adequate method to stop drooling in healthy children is the transposition of Wharton's duct to the floor of the mouth, behind the posterior pillar of the tonsil. In our department, 7 healthy children suffering from drooling underwent this operation with good results. The surgical procedure is fully described and the literature on the subject is reviewed.

Absence spells. Hyperventilation syndrome as a previously unrecognized cause. Absence spells in adults have been recognized in association with disorders of excessive somnolence, transient ischemia of the temporal lobes, and seizure disorders. A 66-year-old man who presented with a history of absence spells for more than 20 years is described. After diagnosis of a hyperventilation syndrome without an associated seizure disorder, educational and behavioral therapy without the use of medication has produced a long, continuing remission of these spells. The hyperventilation syndrome continues to present in many ways, often without recognition by physicians for prolonged periods. The case presented exemplifies this problem and may be the first report of absence spells caused by hyperventilation.

Excellent anti-proliferative and pro-apoptotic effects of (-)-epigallocatechin-3-gallate encapsulated in chitosan nanoparticles on human melanoma cell growth both in vitro and in vivo. Earlier we demonstrated the anti-proliferative and pro-apoptotic effects of green tea polyphenol epigallocatechin-3-gallate (EGCG) on human melanoma cells (Int J Cancer. 2005; 114(4): 513-21). The doses used in this study were not physiologically attainable and for chemoprevention the preferred route of administration is oral consumption. To overcome these shortcomings, and taking advantage of our novel concept of nanochemoprevention (Cancer Res. 2009;69(5):1712-6), we developed a nanotechnology based oral delivery system to encapsulate EGCG. Here, using human melanoma Mel 928 cells we demonstrate 8-fold dose advantage of this nanoformulation over native EGCG. Further, nano-EGCG treated cells showed marked induction of apoptosis and cell cycle inhibition along with the growth of Mel 928 tumor xenograft. Nano-EGCG also inhibited proliferation (Ki-67 and PCNA) and induced apoptosis (Bax, PARP) in tumors harvested from the treated mice. These observations warrant further in vivo efficacy studies of nano-EGCG in robust animal models of human melanoma. This team of investigators developed a nanotechnology based oral delivery system to encapsulate EGCG, a green tea-derived polyphenol in chitosan nanoparticles. Using human melanoma cells, an eight-fold dose advantage was demonstrated over native EGCG, leading to measurable apoptosis induction and proliferation inhibition, warranting further in vivo investigations.

Corrective dermatosurgery in childhood--own experience. Congenital and acquired lesions on children's skin impose great burden upon the children and their parents. These children are frequently faced with various kinds of embarrassment in communication with their peers, ranging from sneering and mockery to isolation. That is why these lesions, especially if readily observable, should be completely removed or at least corrected as soon as possible to enable the child to establish normal communication with the environment and to prevent psychic trauma that may entail serious consequences later in life. Seven pediatric patients burdened with such lesions are presented (naevus papillomatous et verrucosus colli, atrophia linearis cutis faciei, naevus hyperkeratoticus systemicus dorsi, ichthyosis nigra, poikiloderma congenitum, hyalinosis cutis et mucosae, and alopecia post combustionem). Dermabrasion was used in six patients, whereas occipital hair graft transplantation to the alopecic sites was used in a girl with posttraumatic alopecia.

Gelsolin as therapeutic target in Alzheimer's disease. Fibrillar amyloid beta-protein (Abeta) is a major component of amyloid plaques in the brains of individuals with Alzheimer's disease (AD). However, a comprehensive explanation of the mechanisms leading to brain amyloidosis is still pending. Previous studies have identified the anti-amyloidogenic role of gelsolin in AD. Gelsolin can reduce amyloid burden by acting as an inhibitor of Abeta fibrillization, and as an antioxidant and anti-apoptotic protein. Recent evidence indicates reduced brain gelsolin levels in AD. Therefore, a better understanding of the roles of gelsolin in AD pathology, particularly those related with cognition, is required. Most of the information reviewed here relates to experimental studies. However, gelsolin may progress from the present evidence to preclinical and clinical applications. In addition, a greater insight into the environmental factors contributing to abnormally reduced gelsolin function in AD brains may become crucial for the development of much needed disease-modifying strategies. Because, the efficacy of available medicines is still poor, there is an urgent need for novel AD treatments. In this sense, gelsolin could play an important role.

Induction of systemic resistance in plants by biochar, a soil-applied carbon sequestering agent. Biochar is the solid coproduct of biomass pyrolysis, a technique used for carbon-negative production of second-generation biofuels. The biochar can be applied as a soil amendment, where it permanently sequesters carbon from the atmosphere as well as improves soil tilth, nutrient retention, and crop productivity. In addition to its other benefits in soil, we found that soil-applied biochar induces systemic resistance to the foliar fungal pathogens Botrytis cinerea (gray mold) and Leveillula taurica (powdery mildew) on pepper and tomato and to the broad mite pest (Polyphagotarsonemus latus Banks) on pepper. Levels of 1 to 5% biochar in a soil and a coconut fiber-tuff potting medium were found to be significantly effective at suppressing both diseases in leaves of different ages. In long-term tests (105 days), pepper powdery mildew was significantly less severe in the biochar-treated plants than in the plants from the unamended controls although, during the final 25 days, the rate of disease development in the treatments and controls was similar. Possible biochar-related elicitors of systemic induced resistance are discussed.

[Minimally invasive cardiac surgery: surgical techniques and anesthetic problems]. To review current data on minimally invasive cardiac surgery. Search through the Medline data base of French or English articles. The articles were analysed to make a synthesis of the various techniques with their main indications and contra-indications. Minimally invasive cardiac surgery includes various surgical procedures. The usual techniques are described, their major benefits and drawbacks are discussed. The main goals of anaesthetic management are preservation of ventricular function and systemic perfusion, detection and treatment of myocardial ischaemia, prevention of hypothermia in case of coronary artery bypass grafting on the beating heart via sternotomy, intermittent selective ventilation of the collapsed lung using CPAP in case of limited thoracotomy. Expertise in transoesophageal echocardiography is essential for insertion and checking the accurate positioning of the various catheters of the endovascular CPB Heartport system (pulmonary vent, endosinus catheter, venous cannula, endoaortic clamp) allowing coronary artery bypass grafting and mitral valve surgery through limited thoracotomy and finally, detection of retained intracardiac air and assessment of complete clearing of cardiac cavities after mitral valve surgery through limited thoracotomy and aortic valve surgery via ministernotomy. Short-acting anaesthetic agents allow rapid recovery from anaesthesia, early extubation and discharge to the surgical ward within 24 h, whereas overall time spent in the operating room is often longer than with conventional cardiac surgery.

Prognostic impact of microsatellite instability and DNA ploidy in human colon carcinoma patients. Genomic instability in colon cancers is a consequence of chromosomal instability characterized by aneuploidy or defective DNA mismatch repair (MMR) indicated by microsatellite instability (MSI). Given that high-frequency MSI (MSI-H) and diploidy are correlated, we determined whether they are independent prognostic variables. Astler-Coller stage B2 and C colon cancers (N = 528) from patients treated in 5-fluorouracil-based adjuvant therapy trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for hMLH1, hMSH2, and p53 proteins was performed. DNA ploidy was analyzed by flow cytometry. Associations with disease-free and overall survival were determined. MSI-H was detected in 95 tumors (18%), and 70 (74%) of these were diploid. Tumors showing MSI-H (hazard ratio, 0.65; 95% confidence interval, 0.44-0.96; P = .023) or loss of MMR proteins (P = .024) were associated with better overall survival. Improved disease-free and overall survival were found for diploid versus aneuploid/tetraploid tumors (overall survival: hazard ratio, 0.59; 95% confidence interval, 0.43-0.79; P = .0003). In the subgroups of MSI-H and microsatellite stable (MSS)/low-frequency MSI (MSI-L) tumors, diploidy was associated with better survival. The prognostic impact of ploidy was similar in stage B2 and C tumors. Ploidy did not predict the benefit of 5-fluorouracil-based treatment. When ploidy, MSI, and MMR proteins were analyzed in the same multivariate model, only ploidy remained significant. DNA ploidy and MSI-H status were independent prognostic variables, yet ploidy was the strongest marker. Diploidy was associated with better survival in MSI-H and in MSS/MSI-L patient subgroups.

Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis. There have been concerns about validity and accuracy of the measurement of sHLA-G in embryo culture supernatants. In this systematic review, we quantified the diagnostic accuracy of sHLA-G for predicting the ability to achieve clinical pregnancy in women who are undergoing infertility treatment. Medline and Embase were searched up to 7 September 2007, for full English and non-English articles concerning cohort studies evaluating sHLA-G in embryo culture for predicting clinical pregnancy in women undergoing IVF and ICSI. Eleven studies including 1813 patients met our inclusion criteria. In the individual studies, sensitivity ranged from 0.01 to 0.97, specificity from 0.18 to 0.98, the positive likelihood ratio from 0.34 to 3.21 and the negative likelihood ratio from 0.08 to 1.01. These values were highly heterogeneous with, in each case, I(2) values of >75%, and P-values for the Q statistic of <0.001, arguing against generating a pooled estimate for these diagnostic test properties. The diagnostic odds ratios (DORs) ranged from 0.92 to 24.82 in the individual studies with an I(2) value of 49% indicating moderate heterogeneity. Therefore, the meta-analysis combined the logs of the DORs, which are derived from sensitivity and specificity. A random-effects model yielded a summary DOR of 4.38 (95% CI, 2.93-6.55), consistent with modest diagnostic accuracy. Interestingly, an a priori defined subgroup analysis restricted to six studies with good quality embryos showed a better diagnostic performance with a DOR of 12.67 (95% CI, 3.66-43.80) to predict the ability to achieve clinical pregnancy in women undergoing infertility treatment. Further research is needed with single-embryo culture, single-embryo transfer and highly sensitive detection techniques to determine the potential application of measuring sHLA-G in culture supernatant.

[Significance of a new PTH assay (the comparison between whole-PTH and intact-PTH assay)]. It has been shown that intact-PTH assay measures not only full-length biologically active PTH with 84 amino acids, but also some PTH fragments such as (7-84) PTH. Whole-PTH assay is a new method believed to react only with (1-84) PTH. Because circulatory concentrations of various fragments of PTH are very high especially in patients with secondary hyperparathyroidism associated with renal failure, evaluation of PTH levels by whole-PTH assay seems to be useful for accurate assessment of parathyroid function in these patients.

The hard cell: from proteomics to a whole cell model. Proteomics has provided a wealth of data related to the nature of the proteome, including subcellular location, copy number, interaction partners and protein complexes. This raises the question of whether it is feasible to combine these data, together with other data related to overall cellular structure, to construct a static picture of the cell. In this minireview, we discuss these data, and the issues of turning them into whole cell models.

Age-related cell surface proteins of human astrocytoma cells in culture. The 125I labelling patterns of the cell surface proteins of human malignant astrocytoma cells in culture have been analysed with respect to patient age. 125I incorporation into two groups of proteins of MWs 26K and 49K increased with patient age. For the 49K group (but not the 26K group), the tumours tended to segregate into two groups related to tumour grade. These findings may be relevant in the context of the reported patterns of resistance of malignant astrocytoma to chemotherapy and the use of patient age as a prognostic factor for these tumours.

l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial. l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .

Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized. Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease resulting from defective anchoring fibrils at the dermal-epidermal junction and mutations in the type VII collagen gene. In this report, we describe two patients with severe generalized RDEB. Patient 1 was a 24-day-old male infant, and patient 2 was a 1-day-old female infant. Immunofluorescence microscopy demonstrated absence of type VII collagen labeling in a skin sample of patient 1, and reduced staining in patient 2. Electron microscopy revealed absence of anchoring fibrils below the lamina densa in patient 1, and reduced or rudimentary anchoring fibrils in patient 2. Mutation analyses of COL7A1 in these patients revealed heteroallelic recessive mutations which resulted in premature termination codons (PTC): 6573+1G>C in intron81 and 886del6ins14 in exon 7 in patient 1, and 6573+1G>C in intron81 and 4535insC in exon 44 in patient 2. Heteroallelic combinations of PTC mutation generally result in the severe generalized type. Patient 2 has developed a digital fusion at age 2, which is a typical manifestation of severe generalized RDEB. The RDEB subtype is considered to be determined based on comprehensive information, including analysis of alleles, protein expression, ultrastructure and clinical symptoms after growth. However, mutation analyses of COL7A1 can provide valuable information estimating a diagnosis in early infancy.

Purification and characterization of a membrane-associated phosphatidylserine synthase from Bacillus licheniformis. A CDP-diacylglycerol-dependent phosphatidylserine synthase was solubilized from Bacillus licheniformis membranes and purified to near homogeneity. The purification procedure consisted of CDP-diacylglycerol-Sepharose affinity chromatography followed by substrate elution from blue dextran-Sepharose. The purified preparation showed a single band with an apparent relative molecular mass of 53 000 daltons when subjected to sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Proteolytic digestion of the enzyme yielded a smaller (41 000 daltons) active form. The preparation was free of any phosphatidylglycerophosphate synthase, phosphatidylserine decarboxylase, CDP-diacylglycerol hydrolase, and phosphatidylserine hydrolase activities. The utilization of substrates and the formation of products occurred with the expected stoichiometry. Radioisotopic exchange patterns between related substrate and product pairs suggest a sequential Bi-Bi reaction as opposed to the ping-pong mechanism exhibited by the well-studied phosphatidylserine synthase of Escherichia coli [Larson, T. J., & Dowhan, W. (1976) Biochemistry 15, 5212-5218]. The B. licheniformis enzyme was also found to be markedly dissimilar to the E. coli enzyme with regard to association with detergent micelles, affinity for ribosomes, and antigenicity.

[Prognostic factors in resuscitation]. The outcome from intensive care is known to be influenced by such factors as age, previous health status, severity of the disease and diagnosis. In order to assess the influence of each individual factor, 3,687 patients from 38 French intensive care units were studied. For each patient were recorded: age, simplified acute physiological score (SAPS), previous health status, diagnosis, type of intensive care unit (medicine, scheduled or elective surgery) and immediate outcome. Each of these factors was found to influence the immediate survival rate. A multivariate analysis ranked the factors in the following order: SAPS, age, type of intensive care unit and previous health status. Diagnosis played a role in the prognosis since with a 10-15 points SAPS mortality was nil for drug overdose, 12 per cent for chronic obstructive pulmonary disease and 38 per cent for cardiogenic shock. However, a single diagnosis was made in only 37 per cent of the patients, as against 3 diagnoses in 17 per cent and 4 diagnoses or more in 7 per cent. When the type of intensive care unit was considered, the mean death rate was 20 per cent in medicine, 27 per cent in scheduled surgery and 5 per cent in elective surgery (P less than 0.001). Since this study showed a definite influence of each of the four factors on immediate survival, intensive care patients can be described and classified according to this system. However, it must be stressed that individual prognoses are extremely vague.

Immobilized pH gradients (IPG) simulator--an additional step in pH gradient engineering: II. Nonlinear pH gradients. While in the companion paper (Tonani, C. & Righetti, P. G., Electrophoresis 1991, 12, 1011-1021) we gave the general outline of our new computer program, immobilized pH gradients (IPG) simulator, able to simulate and optimize linear pH gradients for isoelectric focusing in immobilized pH gradients, in the present report we extend the application of such a program to: (i) convex exponential gradients, (ii) logarithmic and (iii) polynomial gradients. Such gradients are meant to give equal space to protein spots in complex protein mixtures (e.g., cell lysates, biological fluids) and follow the statistical distribution of protein pI values along the pH axis. They will prove of fundamental importance in two-dimensional maps, both because they optimize the spreading of spots in the two-dimensional plane and because of the excellent reproducibility of immobilized pH gradients. The following concave exponential recipes are given: pH 3-8, pH 3-9, pH 3-10, pH 3-11, pH 4-7, pH 4-8, pH 4-9, pH 4-10, pH 4-11, pH 5-8, pH 5-9, and pH 5-10, as well as the most extended pH 2.5-11 interval. Two interesting logarithmic gradients are described: pH 3-6 and pH 3-7 and one sigmoidal (derived with a polynomial of 5th degree): pH 3-11.

Two-dimensional π-conjugated metal-organic nanosheets as single-atom catalysts for the hydrogen evolution reaction. The design and synthesis of electrocatalysts with controllable active sites are highly desirable for producing hydrogen. Inspired by the experimental realization of two-dimensional metal-organic framework (2D-MOF) nanosheets, a computational screening was performed to find out the optimal single-atom catalysts for the hydrogen evolution reaction (HER) from 36 2D-MOFs composed of transition metal and benzene-like molecular ligands. Through first-principles calculations, six configurations were identified as potential catalysts for the HER with performance comparable to those of Pt-based catalysts due to the near-zero Gibbs free energy and favourable activation barriers originating from their appropriate d-orbital bonding mechanism with atomic hydrogen.

The Effect of Fluorescent Protein Tags on Phosphoglycerate Kinase Stability Is Nonadditive. It is frequently assumed that fluorescent protein tags used in biological imaging experiments are minimally perturbing to their host protein. As in-cell experiments become more quantitative and measure rates and equilibrium constants, rather than just "on-off" activity or the presence of a protein, it becomes more important to understand such perturbations. One criterion for a protein modification to be a perturbation is additivity of two perturbations (a linear effect on the protein free energy). Here we show that adding fluorescent protein tags to a host protein in vitro has a large nonadditive effect on its folding free energy. We compare an unlabeled, three singly labeled, and a doubly labeled enzyme (phosphoglycerate kinase). We propose two mechanisms for nonadditivity. In the "quinary interaction" mechanism, two tags interact transiently with one another, relieving the host protein from unfavorable tag-protein interactions. In the "crowding" mechanism, adding two tags provides the minimal crowding necessary to overcome destabilizing interactions of individual tags with the host protein. Both of these mechanisms affect protein stability in cells; we show here that they must also be considered for tagged proteins used for reference in vitro.

Job satisfaction of college graduates with learning disabilities. Job satisfaction, as assessed via five scales that posed questions concerning colleagues, work, supervision, pay, and promotion, as well as overall total job satisfaction, was examined for 55 self-identified college graduates with learning disabilities (LD) and 55 control graduates matched by gender, major, degree, and graduation year. All participants graduated from a competitive midwestern university from 1987 to 1994 and represented advantaged groups when compared to both LD and non-LD populations. The graduates with LD required significantly more time to complete their degrees and showed significantly lower CPAs. Data analysis indicated that the graduates with LD perceived themselves as receiving significantly less pay and promotion opportunities, and reported less total job satisfaction, than graduates without LD. However, no significant salary differences between the groups were found. The implications of these findings are examined.

Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. A number of natural phenolic compounds display antioxidant and cell protective effects in cell culture models, yet in some studies show prooxidant and cytotoxic effects. Pancreatic beta-cells have been reported to exhibit particular sensitivity to oxidative stress, a factor that may contribute to the impaired beta-cell function characteristic of diabetes. The aim of this study was to examine the potential of natural phenolics to protect cultured pancreatic beta-cells (betaTC1 and HIT) from H(2)O(2) oxidative stress. Exposure of cells to H(2)O(2) led to significant proliferation inhibition. Contrary to what one should expect, simultaneous exposure to H(2)O(2) and the phenolics, quercetin (10-100 microM), catechin (50-500 microM), or ascorbic acid (100-1000 microM), led to amplification of proliferation inhibition. At higher concentrations, these compounds inhibited proliferation, even in the absence of added H(2)O(2). This prooxidant effect is attributable to the generation of H(2)O(2) through interaction of the added phenolic compounds with as yet undefined componenets of the culture media. On the other hand, inclusion of metmyoglobin (30 microM) in the culture medium significantly reduced the prooxidant impact of the phenolics. Under these conditions, quercetin and catechin significantly protected the cells against oxidative stress when these components were present during the stress period. Furthermore, significant cell protection was observed upon preincubation of cells with chrysin, quercetin, catechin, or caffeic acid (50 microM, each) prior to application of oxidative stress. It is concluded that provided artifactual prooxidant effects are avoided, preincubation of beta-cells with relatively hydrophobic natural phenolics can confer protection against oxidative stress.

Investigation of a cylindrical ultrasound phased-array with multiple-focus scanning for breast tumor thermal therapy. The purpose of this study is to investigate the feasibility of a cylindrical ultrasound phased-array with multiple-focus scanning strategy to produce a uniform heating for breast thermal therapy. In this study, a breast is surround by a 1-MHz cylindrical ultrasound phased-array consists of 200 elements with a radius of 10 cm and a height of 2 cm. To prevent overheating in the normal tissue, a scanning region of 1 cmt x 1 cm was selected as a single heating unit. Planning target volume (PTV) larger than this size would be divided into several sub-heating units, and then be treated sequentially with cooling phase to prevent overheating in the surrounding normal tissue. Parameters such as the target temperature, blood perfusion rate and the size of PTV are evaluated. Simulation results show that the target temperature affects the thermal lesion size and the blood perfusion rate increases the heating time significantly. This method provides efficient heating for breast tumor thermal therapy while preventing overheating the ribs.

Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury. The purpose of this study is to evaluate the effectiveness of a shorter course of Dialectical Behavior Therapy (DBT) in enhancing treatment retention and reducing: urges to engage in non-suicidal self injury (NSSI), NSSI, suicide ideation, and subjective distress in borderline personality disorder (BPD). Twenty patients with BPD received a six-month course of Dialectical Behavior Therapy (DBT-B). DBT-B was delivered in the standard manner except for the shortened duration from one-year minimum to six months. All variables were measured at baseline, and at six months. Data were analyzed using paired t-tests. Treatment retention rate was 95%. Significant reductions were found in NSSI urges, NSSI, suicide ideation, subjective distress, depression, and hopelessness between baseline and six months. These results support the use of DBT-B in a six-month format when NSSI and suicidal behavior and ideation are the targeted behaviors. Target behaviors were reduced significantly and retention was extremely high in comparison to other interventions for this population. A large scale randomized controlled trial investigating its efficacy is warranted to determine if the results can be replicated and if improvement can be sustained.

Extracolonic Findings at Screening CT Colonography: Prevalence, Benefits, Challenges, and Opportunities. Extracolonic findings at screening CT colonography (CTC) represent imaging findings incidentally detected outside the colon and rectum. Confusion regarding rates reported in the literature fuels controversy over the relative benefits versus harms of extracolonic findings. From an evidence-based approach, this article reviews the prevalence and benefits of and challenges raised by extracolonic findings, as well as opportunities to further leverage the effect of screening CTC. The role of the radiologist in handling these lesions responsibly is emphasized.

Predictive factors, efficacy, and safety of balloon post-dilation after transcatheter aortic valve implantation with a balloon-expandable valve. This study sought to evaluate the predictive factors, effects, and safety of balloon post-dilation (BPD) for the treatment of significant paravalvular aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI). Very few data exist on BPD after TAVI with a balloon-expandable valve. A total of 211 patients who underwent TAVI with a balloon-expandable valve were included. BPD was performed after TAVI if paravalvular AR ≥ 2 was identified by transesophageal echocardiography. Clinical events and echocardiographic data were prospectively recorded, and median follow-up was 12 (6 to 24) months. BPD was performed in 59 patients (28%), leading to a reduction in at least 1 degree of AR in 71% of patients, with residual AR <2 in 54% of the patients. The predictors of the need for BPD were the degree of valve calcification and transfemoral approach, with valve calcification volume >2,200 and >3,800 mm(3) best determining the need for and a poor response to BPD, respectively. Patients who underwent BPD had a higher incidence of cerebrovascular events at 30 days (11.9% vs. 2.0%, p = 0.006), with most (83%) events within the 24 h after the procedure occurring in patients who had BPD. No significant changes in valve area or AR degree were observed at follow-up in BPD and no-BPD groups. BPD was needed in about one-fourth of the patients undergoing TAVI with a balloon-expandable valve and was successful in about one-half of them. A higher degree of valve calcification and transfemoral approach predicted the need for BPD. BPD was not associated with any deleterious effect on valve function at mid-term follow-up, but a higher rate of cerebrovascular events was observed in patients who had BPD.

Molecular epidemiology and virulence characteristics of prevalent group A streptococci recovered from patients in northern India. In this study, the prevalence of M types of Group A Streptococcus (GAS) in North India, invasive behavior of prevalent M types, and inflammatory immune response by host cells were studied. A total of 1,047 clinical samples were collected between 2004 and 2010. Confirmation of GAS was determined by serotyping and M types were identified by emm gene sequencing. The most prevalent serotypes were selected to study their invasive behavior and inflammatory immune response under different temperatures and salt concentrations in A549 and HEp-2 cells. Ninety-two isolates were identified as GAS of which 17 were M types with 18.5% heterogeneity. The most prevalent M types were M1 (21.73%) and M49 (8.7%), respectively. M1 and M49 were used to study virulence potential and inflammatory immune responses. The efficiency of cell infection decreased with increased temperature for both M types, increasing with lowering temperatures compared to the uninfected control (37°C). As salt concentration was increased, cell infection efficiency was lowered with some exceptions; the infection efficiency of M1 strain in A549 cells with 0.6 M NaCl was 50 fold higher (p ≤ 0.03). Significantly increased production of IL-6 and IL-8 was observed in both cell lines infected with GAS and when grown under different environmental conditions compared to uninfected cell lines. This study determined the prevalence of different M types in North India and showed that environmental conditions can regulate cell infection by GAS . This information may influence the selection of GAS serotypes used in vaccine development.

Stability of bacteriophage type of Mycobacterium tuberculosis: absence of variation caused by experimental chemotherapy in mice and analysis of spontaneous variation. The bacteriophage typing of 54 strains isolated from the tissues of mice infected with the strain H37Rv of Mycobacterium tuberculosis and treated with isonazid and rifampin showed that the bacteriophage type did not change. The fluctuation analysis of populations of the tubercle bacilli demonstrated that the rate of mutation from sensitivity to resistance in respect to the bacteriophage DS6A was less than 1.3 X 10(-8) mutations per bacterium per generation.

[Medical treatment of fragile X syndrome]. There is still no medication for fragile X syndrome (FXS) which acts directly on the genetic mechanisms or on the immediate result of the genetic defect. However, behavioral and cognitive manifestations can be approached from both the psychological/educational and pharmacological sides. Both approaches are not mutually exclusive but are complementary and synergic. There are currently potent drugs which can improve important symptoms of the FXS, behavioral disorders, hyperactivity, attention deficit, obsessive disorders and anxiety. Pharmacological treatment can be useful: CNS stimulants, clonidine, folic acid, serotonin reuptake inhibitors, and atypical antipsychotics. Pharmacological treatment of epilepsy is needed whenever epilepsy occurs. There is no specific antiepileptic for FXS, so action must be taken with the most efficient antiepileptic according to the crisis type, evaluating tolerance and possible effects on behavior. Insomnia is also of interest in children with FXS. In this case the use of melatonin can be of great help.

Carrier Extraction from Perovskite to Polymeric Charge Transport Layers Probed by Ultrafast Transient Absorption Spectroscopy. The efficiency of state-of-the-art perovskite solar cells is limited by carrier recombination at defects and interfaces. Thus, understanding these losses and how to reduce them is the way forward toward the Shockley-Queisser limit. Here, we demonstrate that ultrafast transient absorption spectroscopy can directly probe hole extraction and recombination dynamics at perovskite/hole transport layer (HTL) interfaces. To illustrate this, we employed PDPP-3T as HTL because its ground-state absorption is at lower energy than the perovskite's photobleach, enabling direct monitoring of interfacial hole extraction and recombination. Moreover, by fitting the carrier dynamics using a diffusion model, we determined the carrier mobility. Afterwards, by varying the perovskite thickness, we distinguished between carrier diffusion and carrier extraction at the interface. Lastly, we prepared device-like structures, TiO2/perovskite/PDPP-3T stacks, and observed reduced carrier recombination in the perovskite. From PDPP-3T carrier dynamics, we deduced that hole extraction is one order faster than recombination of holes at the interface.

Zebrafish caspase-3: molecular cloning, characterization, crystallization and phylogenetic analysis. Apoptosis plays an important role in maintaining the normal function of various tissues and organs in different species. Caspase-3 is a terminal caspases which plays an important role in the execution of apoptosis in all vertebrates. It was cloned from zebra fish embryos and its properties were identified through Western blotting and biological activity. In the cells over-expressing caspase-3, Western blotting with an anti-His-tag antibody confirmed the presence of caspase-3 in the three bands that were proposed to correspond to the precursor form (33 kDa), the mature forms processed at the prodomain alone (29 kDa, large subunit) and small sub unit (13 kD). Fish kidney cells were transiently co-transfected with the beta-galactosidase reporter gene and either vector alone (mock), pZCASP3His (caspase-3) or pZCASP3His mutant (caspase-3 mutant). After 72 h following transfection of fish kidney cells, 35% of cells transfected with the zebra fish caspase-3 construct, pZCASP3His, showed apoptotic morphology when compared with cells transfected with the mock vector or an expression construct (pZCASP3His mutant) encoding the caspase-3 mutant lacking Cys. The fusion proteins were expressed in Escherichia coli, isolated from cell lysates by nickel-affinity column chromatography, and cleaved with thrombin. A thrombin cleavage recognition site was positioned at the fusion junction to release the caspase-3 from the fusion protein. Phylogenetic analysis showed that the cloned zebra fish caspase was a member of the caspase-3 subfamily with approximately 60% identity with caspase-3 from Xenopus, chicken and mammals. We have obtained structural information by X-ray crystallography. Orthorhombic crystals of the caspase-3 that diffracted to 1.8 A were obtained in a mixture of 0.1 M imidazole (pH 6.0) and 0.4 M NaOAc (pH 7.0 -7.5), containing 30% glycerol. The space group is C222 with cell dimensions of a = 36.07 A, b = 38.80 A, c = 135.20 A.

Clinical significance of the expression of estrogen receptors alpha and beta for endocrine therapy of breast cancer. The assessment of the estrogen receptor (ER) alpha and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. ERbeta, a more recently discovered ER, may influence estrogen action through the ERalpha pathway. To evaluate the clinical significance of these receptors in the response to endocrine therapy, we investigated their expression in primary breast cancer tissues. ERalpha and PgR were evaluated using immunohistochemistry (IHC) and enzyme immunoassay (EIA) and ERbeta expression was determined using IHC and reverse transcription-polymerase chain reaction. When the cut-off level of EIA was set at 13 fmol/mg protein for ERalpha and that for IHC was set as an IHC score between 2 and 3, a significant correlation between ERalpha EIA and IHC was seen (concordance rate 88.4%). This indicates that this cut-off level of ERalpha IHC can be adopted to quantify breast cancer prognoses. Furthermore, the tumors with positive expression of ERalpha IHC or PgR IHC using this criterion were significantly related to the response to endocrine therapy. Additionally, tumors with positive expression of ERbeta wild-type tended to have a better response to endocrine therapy than negative ones, and tamoxifen responders tended to exhibit a lower ratio of ERbetacx (one of the ERbeta variants) to ERbeta wild-type than nonresponders. The results concerning ERbeta are not yet fully understood; further investigations and evaluations should analyze the role of ERbeta wild-type and variant type in breast cancer treatment.

Desflurane and sevoflurane elimination kinetics and recovery quality in horses. To evaluate pharmacokinetics, recovery times, and recovery quality in horses anesthetized with 1.2 times the minimum alveolar concentration of sevoflurane or desflurane. 6 healthy adult horses. Anesthesia was maintained with sevoflurane or desflurane for 2 hours at 1.2 times the minimum alveolar concentration. Horses recovered without assistance. During recovery, end-tidal gas samples were collected until horses spontaneously moved. Anesthetic concentrations were measured by use of gas chromatography. After a 1-week washout period, horses were anesthetized with the other inhalation agent. Video recordings of anesthetic recovery were evaluated for recovery quality on the basis of a visual analogue scale by investigators who were unaware of the anesthetic administered. Anesthetic washout curves were fit to a 2-compartment kinetic model with multivariate nonlinear regression. Normally distributed interval data were analyzed by means of paired Student t tests; ordinal or nonnormally distributed data were analyzed by means of Wilcoxon signed rank tests. Horses recovered from both anesthetics without major injuries. Results for subjective recovery evaluations did not differ between anesthetics. Area under the elimination curve was significantly smaller and time to standing recovery was significantly less for desflurane than for sevoflurane, although distribution and elimination constants did not differ significantly between anesthetics. Differences in area under elimination the curve between anesthetics indicated more rapid clearance for desflurane than for sevoflurane in horses, as predicted by anesthetic blood solubility differences in this species. More rapid elimination kinetics was associated with faster recovery times, but no association with improved subjective recovery quality was detected.

Assessing the disease burden due to epilepsy by disability adjusted life year in rural China. To demonstrate the application of Disability Adjusted Life Year (DALY) as an aid in health outcome measures to evaluate the epilepsy disease burden in rural China and to provide Chinese data to achieve a better understanding of disease burden due to epilepsy. The DALY is the sum of the number of years of survival with disability (Years Lived with Disability, YLD) and the number of years lost because of premature mortality (Years of Life Lost, YLL). We calculated the YLD based on the prevalence survey of epilepsy among 66,393 people sampled in Heilongjiang, Henan, Jiangsu, Ningxia, Shanghai, and Shanxi provinces in 2000. The epilepsy mortality data from Chinese literature provided the YLL due to epilepsy. We applied sensitivity analysis to evaluate the influence of uncertainty on the epilepsy mortality value and disability weight in the study. In 2000, epilepsy caused 1.83 and 2.48 DALY lost per 1,000 population in Henan and Ningxia province, which had the lowest and the highest DALY lost among the six study areas. Overall, epilepsy caused 1.41 YLLs and 0.67 YLDs per 1,000 population; thus the DALYs lost because of epilepsy was 2.08 per 1,000 population, representing the epilepsy disease burden in rural China. The DALY measure, which includes the extent of disability from epilepsy, provides a useful tool for the epilepsy disease burden assessment. The disease burden of epilepsy in China is considered higher than previous estimations.

EMOTIONAL REPERCUSSIONS AND QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS UNDERGOING HEMODIALYSIS OR AFTER KIDNEY TRANSPLANTATION. To investigate the emotional repercussions and quality of life (QOL) associated with end-stage kidney disease (ESKD) in children and adolescents undergoing hemodialysis or a kidney transplant (TX). We conducted a quantitative-qualitative study. 48 children and adolescents with ESKD were interviewed; half of them underwent hemodialysis treatment, and the other half had a kidney transplantation. Their respective 48 caregivers also participated in the study. The questionnaire involved both the Pediatric Quality of Life Inventory and a thematic story-drawing tool. An analysis of the QOL questionnaire's results was done by comparing the sum of points between groups and the theme-based story-drawing consisted of interpreting the data contained in the material using Freudian and Lacanian theories. In the QOL questionnaires, the total score was higher in the transplanted patients and in their caregivers, suggesting a perception of better QOL after kidney transplantation. In the specific aspects of the questionnaire, physical capacity was considered superior by children who underwent transplants and their caregivers. There were no differences between the groups in the emotional, social and school aspects. However, the caregivers of the patients who had a transplant perceived a significant difference in QOL in the school aspect. In the thematic story-drawings, emotional suffering in the two analyzed groups was evidenced regardless of the treatment. Despite the questionnaire results suggesting that transplantation does improve some aspects of QOL, there were no differences observed between kidney replacement therapies regarding the emotional repercussion of chronic kidney disease.

Hydrogeomorphology explains acidification-driven variation in aquatic biological communities in the Neversink Basin, USA. Describing the distribution of aquatic habitats and the health of biological communities can be costly and time-consuming; therefore, simple, inexpensive methods to scale observations of aquatic biota to watersheds that lack data would be useful. In this study, we explored the potential of a simple "hydrogeomorphic" model to predict the effects of acid deposition on macroinvertebrate, fish, and diatom communities in 28 sub-watersheds of the 176-km2 Neversink River basin in the Catskill Mountains of New York State. The empirical model was originally developed to predict stream-water acid neutralizing capacity (ANC) using the watershed slope and drainage density. Because ANC is known to be strongly related to aquatic biological communities in the Neversink, we speculated that the model might correlate well with biotic indicators of ANC response. The hydrogeomorphic model was strongly correlated to several measures of macroinvertebrate and fish community richness and density, but less strongly correlated to diatom acid tolerance. The model was also strongly correlated to biological communities in 18 sub-watersheds independent of the model development, with the linear correlation capturing the strongly acidic nature of small upland watersheds (< 1 km2). Overall, we demonstrated the applicability of geospatial data sets and a simple hydrogeomorphic model for estimating aquatic biological communities in areas with stream-water acidification, allowing estimates where no direct field observations are available. Similar modeling approaches have the potential to complement or refine expensive and time-consuming measurements of aquatic biota populations and to aid in regional assessments of aquatic health.

Percolation thresholds and Fisher exponents in hypercubic lattices. We use invasion percolation to compute highly accurate numerical values for bond and site percolation thresholds p_{c} on the hypercubic lattice Z^{d} for d=4,...,13. We also compute the Fisher exponent τ governing the cluster size distribution at criticality. Our results support the claim that the mean-field value τ=5/2 holds for d≥6, with logarithmic corrections to power-law scaling at d=6.

Occurrence and distribution of yellow grub trematodes (Clinostomum complanatum) infection in Taiwan. Digenetic trematodes of the genus Clinostomum are widely distributed in many species of freshwater fish and are known to cause the zoonotic disease Halzoun. Humans may become accidental hosts if they ingest raw freshwater fish containing metacercaria of Clinostomum complanatum, which causes pharyngitis or laryngitis. The yellow grub parasitizing cultivated ayu (Plecoglossus altivelis) and loach (Misgurnus anguillicaudatus) was one of the most serious problems in fish farms from 1977 to 1979 in Taiwan. The present study revealed, for the first time, frequent occurrence of C. complanatum metacercaria in various fish species in a natural environment, the Dahan River, in Taiwan. We examined 1503 fish specimens belonging to four families and 162 snails representing six species. C. complanatum metacercaria was mainly from the fish family Cyprinidae, and only cercaria from the snail Radix swinhoei was recovered. The prevalence and mean intensity of metacercaria were 9.8% and 9.35 parasites/infected fish, respectively. The prevalence of cercaria was low, 0.62%, in snails. Acrossocheilus paradoxus, Zacco barbata, Zacco pachycephalus, Zacco platypus, Onychostoma barbatula, and Hemibarbus labeo are new host records. Metacercariae were primarily found in the operculum, mandible, muscle, and oral cavity of fish. Morphological description and molecular analysis with 18S rDNA sequencing allowed for rapidly identifying C. complanatum. Encysted and excysted metacercariae cultivated at 22 °C in physiological saline died within 60 h. The mean intensity of infection increased with an increasing length of Z. pachycephalus. We found no association between monthly parasite prevalence and mean intensity at each sampling location. No C. complanatum metacercaria survived after 8 h of salting. The Dahan River has suitable conditions and hosts (snails, fish, and fish-eating birds) for maintaining the life cycle of C. complanatum.

[In vitro antibacterial activity of rokitamycin, a new macrolide antibiotic. Results of a multicenter study]. Minimal inhibitory concentrations (MIC) of rokitamycin (R) were evaluated by agar dilution for 914 bacterial strain isolated in 4 hospitals and classed as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramines group (MLS). MICs of R ranged from 0.06 to 1 microgram/ml (mode MIC 0.25-0.5) on Staphylococci susceptible to MLS and on MLSB inducible strains; R was inactive on MLSB constitutive strains. MICs of R ranged from 0.008 to 0.5 microgram/ml (mode MIC 0.06 to 0.25) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.06 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.06 to 0.5 microgram/ml (mode MIC 0.5) and strains resistant to E by 0.25 to greater than 128. Haemophilus were inhibited by 0.5 to 0.65 microgram/ml (mode MICs of R ranged generally from 0.016 to 0.5 microgram/ml (mode MIC 0.12) for C. perfringens and from 0.016 to 1 (mode MIC 0.06) for B. fragilis. Thus, R was shown to be among macrolide antibiotics of resistance strains. Its activity was superior to that of other products of this group spiramycin, josamycin, miokamycin, particularly on Gram positive cocci. R had a good activity on Neisseria, Branhamella, anaerobes and, as others macrolides, was poorly active on Haemophilus.

Monte Carlo simulation of the effect of focal spot size on contrast-detail detectability. A contrast-detail experiment was simulated using Monte Carlo methods, to test the hypothesis that quantum limitations lead to an optimum minimum focal spot size below which no further improvement in image quality may be obtained. The simulation included a variable X-ray tube focal spot size, patient equivalent water phantom, X-ray couch, automatic exposure control, anti-scatter grid and indirect digital radiography detector. A number of simplifications were necessary in order to limit the calculation time to 8 days per image. Four images were produced for each focal spot size and these were scored by eight experienced observers. The contrast-detail curves were found to improve monotonically as focal spot size was reduced, with the best images produced by a point source. This contradicts the hypothesis of quantum limitation of focal spot size. We conclude that further work is required on the optimization of focal spot size. To assist with this, a new definition of system detective quantum efficiency is suggested, that includes the focal spot modulation transfer function, but does not include scattered radiation from the patient.

Optimal designs for group randomized trials and group administered treatments with outcomes at the subject and group level. With group randomized trials complete groups of subject are randomized to treatment conditions. Such grouping also occurs in individually randomized trials where treatment is administered in groups. Outcomes may be measured at the level of the subject, but also at the level of the group. The optimal design determines the number of groups and the number of subjects per group in the intervention and control conditions. It is found by taking a budgetary constraint into account, where costs are associated with implementing the intervention and control, and with taking measurements on subject and groups. The optimal design is found such that the effect of treatment is estimated with highest efficiency, and the total costs do not exceed the budget that is available. The design that is optimal for the outcome at the subject level is not necessarily optimal for the outcome at the group level. Multiple-objective optimal designs consider both outcomes simultaneously. Their aim is to find a design that has high efficiencies for both outcome measures. An Internet application for finding the multiple-objective optimal design is demonstrated on the basis of an example from smoking prevention in primary education, and another example on consultation time in primary care.

Polarizabilities and hyperpolarizabilities for the atoms Al, Si, P, S, Cl, and Ar: Coupled cluster calculations. Accurate static dipole polarizabilities and hyperpolarizabilities are calculated for the ground states of the Al, Si, P, S, Cl, and Ar atoms. The finite-field computations use energies obtained with various ab initio methods including Moller-Plesset perturbation theory and the coupled cluster approach. Excellent agreement with experiment is found for argon. The experimental alpha for Al is likely to be in error. Only limited comparisons are possible for the other atoms because hyperpolarizabilities have not been reported previously for most of these atoms. Our recommended values of the mean dipole polarizability (in the order Al-Ar) are alpha/e(2)a(0) (2)E(h) (-1)=57.74, 37.17, 24.93, 19.37, 14.57, and 11.085 with an error estimate of +/-0.5%. The recommended values of the mean second dipole hyperpolarizability (in the order Al-Ar) are gamma/e(4)a(0) (4)E(h) (-3)=2.02 x 10(5), 4.31 x 10(4), 1.14 x 10(4), 6.51 x 10(3), 2.73 x 10(3), and 1.18 x 10(3) with an error estimate of +/-2%. Our recommended polarizability anisotropy values are Deltaalpha/e(2)a(0) (2)E(h) (-1)=-25.60, 8.41, -3.63, and 1.71 for Al, Si, S, and Cl respectively, with an error estimate of +/-1%. The recommended hyperpolarizability anisotropies are Deltagamma/e(4)a(0) (4)E(h) (-3)=-3.88 x 10(5), 4.16 x 10(4), -7.00 x 10(3), and 1.65 x 10(3) for Al, Si, S, and Cl, respectively, with an error estimate of +/-4%.

ACR Appropriateness Criteria® follow-up and retreatment of brain metastases. Multiple options for retreatment are available, which include whole-brain radiation therapy, stereotactic radiosurgery, surgery, chemotherapy, and supportive care. Size, number, timing, location, histology, performance status, and extracranial disease status all need to be carefully considered when choosing a treatment modality. There are no randomized trials examining the retreatment of brain metastases. Repeat whole-brain radiation has been examined in a single-institution experience, showing the potential for clinical responses in selected patients. Local control rates as high as 91% using stereotactic radiosurgery for relapses after whole-brain radiation are reported. Surgery can be indicated in progressive and/or hemorrhagic lesions causing mass effect. The role of chemotherapy in the recurrent setting is limited but some agents may have activity on the basis of experiences on a smaller scale. Supportive care continues to be an important option, especially in those with a poor prognosis. Follow-up for brain metastases patients is discussed, examining the modality, frequency of imaging, and imaging options in differentiating treatment effect from recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of the current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Iwr1 directs RNA polymerase II nuclear import. RNA polymerase (Pol) II transcribes protein-coding genes in the nucleus of eukaryotic cells and consists of 12 polypeptide subunits. It is unknown how Pol II is imported into the nucleus. Here we show that Pol II nuclear import requires the protein Iwr1 and provide evidence for cyclic Iwr1 function. Iwr1 binds Pol II in the active center cleft between the two largest subunits, maybe facilitating or sensing complete Pol II assembly in the cytoplasm. Iwr1 then uses an N-terminal bipartite nuclear localization signal that is recognized by karyopherin α to direct Pol II nuclear import. In the nucleus, Iwr1 is displaced from Pol II by transcription initiation factors and nucleic acids, enabling its export and recycling. Iwr1 function is Pol II specific, transcription independent, and apparently conserved from yeast to human.

Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat. In the rat, as in most other polytocous species, fetuses tend to be relatively evenly spaced along the uterine horn, perhaps to minimize possible effects of local overcrowding on placental function and fetal growth. Here we administered 2 mg of indomethacin, in split doses on day 5 of gestation, in an attempt to disturb evenness of spacing and so reveal local overcrowding effects, if any. The effects on spacing, expressed as the coefficient of deviation of distances between neighboring implants (CVd%) and correlations between fetal and placental weights and distance to neighbors, was examined on day 16 and day 22 of gestation to cover the period of rapid fetal growth. Indomethacin markedly affected evenness of spacing; at day 16, CVd% increased from a control value of 19.2 to 50.8% and at day 22 from 27.5 to 41.2%. Despite the increased variability of spacing and consequent local crowding, including examples of conjoined placentas in the treated rats, there was no evidence that these local factors affected placental growth or weight of individual fetuses. Indomethacin, however, had a general effect on placental and fetal growth. At day 16, mean fetal weights were retarded but by day 22 had caught up to those of control litters, and this was accompanied by significant placental hypertrophy. Collectively, these results show that the uterus has sufficient reserve to cope with relatively uneven spacing of fetuses and have provided a model for examining catch-up growth of fetuses and accompanying placental changes.

[Control of disordered wound healing using sonography based on postoperative follow-up after TEP implantation]. Clinical diagnosis of early postoperative complications remains a major issue in patients undergoing total hip replacement. Early diagnosis is essential because (clinical) signs of inflammations as fever or elevated white blood count already reflecting late complications. The goal of our study was to evaluate postoperative monitoring for early detection and treatment of hematoma and abscess following total hip replacement. 308 patients undergoing total hip replacement were postoperatively monitored for the development of hematoma and abscess, comparing routine ultrasound to on demand ultrasound in case of clinical signs of infection. The diagnostic puncture was 6.5% (10/154) in group A (on demand ultrasound) versus 11.7% (18/154) in group B (routine ultrasound). Infections were seen in 5.2% (8/154) of patients in group A compared to 0.6% (1/154) in group B, leading to surgical intervention in 3.3% (5/154) group A, respectively 0.6% (1/154) in group B.

Molecular cloning and characterization of all RND-type efflux transporters in Vibrio cholerae non-O1. Resistance Nodulation cell Division (RND) efflux transporters are thought to be involved in mediating multidrug resistance in Gram-negative bacteria, including Vibrio cholerae non-O1. There are six operons for putative RND-type efflux transporters present in the chromosome of V. cholerae O1 including two operons, vexAB and vexCD, which had already been identified. All of the six operons were cloned from V. cholerae non-O1, NCTC4716 by the PCR method, introduced, and expressed in cells of drug hypersusceptible Escherichia coli KAM33 (DeltaacrAB, DeltaydhE). Only vexEF conferred elevated minimum inhibitory concentrations (MICs) of some antimicrobial agents in the E. coli cells. However, VexEF did not confer increased MIC of any drug tested in tolC-deficient E. coli KAM43 cells. On the other hand, when E. coli KAM43 was transformed with vexAB, vexCD or vexEF together with tolC(Vc) of V. cholerae NCTC4716, we observed elevated MICs of various antimicrobial agents. Among them, E. coli KAM43 expressing both VexEF and TolC(Vc) showed much higher MICs and much broader substrate specificity than the other two. We also observed ethidium efflux activity via VexEF-TolC(Vc), and the activity required Na(+). Thus, VexEF-TolC (Vc) is either a Na(+)-activated or a Na(+)-coupled transporter. To our knowledge, this is the first report on the requirement of Na(+) for an RND-type efflux transporter.

Poliovirus infection and Bell's palsy in children. During a 16-months study period at Vellore, South India, three out of five children presenting as 'Bell's palsy' were suffering from poliomyelitis. In polio-endemic countries, poliomyelitis should be considered when children present as 'Bell's palsy'.

Neuroma of the distal posterior interosseous nerve as a cause of persistent dorsal wrist pain. Dorsal wrist pain is a very common cause of complaint in the clinical practice of the hand surgeon. Such pain can frequently be related to traumatic, inflammatory or degenerative diseases, but sometimes its origin is far away from these common causes. A rare case is reported of chronic dorsal wrist pain of neuropathic origin, due to a pre-capsular neuroma of the posterior interosseous nerve. Possible causes, diagnostic hints, and treatment options are thoroughly discussed.

Centromere proteins. I. Mitosis specific centromere antigen recognized by anti-centromere autoantibodies. Human anti-centromere sera from scleroderma patients were used to detect centromere antigens of mouse fibroblast cells. An Mr = 59,000 centromere protein was localized exclusively on mitotic chromosomes. The association of this protein with the mitotic chromosomes proved to be DNase I sensitive. In interphase nuclei, this centromere antigen was not detectable by immunoblot techniques. The results suggest that the Mr = 59,000 mitosis specific protein may be necessary for the structural stability of kinetochores during mitosis.

Endocrine function in sclerosteosis. Sclerosteosis is a rare autosomal recessive condition which is characterized by excessive skeletal overgrowth, distortion of the facies, cranial nerve abnormalities and raised intracranial pressure. Syndactyly and digital malformation are associated features. Radiological examination reveals thickened sclerotic bone maximally involving the skull, including the pituitary fossa. Sclerosis and hyperostosis are present throughout the skeleton. Biochemical and endocrine tests were carred out on 3 patients with sclerosteosis in an attempt to detect any dysfunction of calcium regulation of the pituitary. Results revealed no abnormality of basal parathyroid or calcitonin secretion. Histological examination revealed quantitatively increased bone resorption in comparison with normal subjects, although the pattern resembled osteosclerosis. Regulation of growth hormone, adrenocorticotrophin, gonadotrophin and thyrotrophin function were intact. We conclude that pituitary function and calcium 'homeostasis' are normal in this disorder.

Dentinal damage and fracture resistance of oval roots prepared with single-file systems using different kinematics. Vertical root fracture is a common finding in endodontically treated teeth, notably oval roots. The aim of the present study was to determine the effect of instrumentation kinematics and the material of instrument construction of single-file systems on dentin walls and fracture resistance of oval roots. Sixty-five roots with oval canals were allocated into a control group (n = 5) and 3 experimental groups of 20 roots each. Group WO was instrumented with the WaveOne primary file (Dentsply Maillefer, Baillagues, Switzerland), group PT-Rec was prepared with F2 ProTaper files (Dentsply Maillefer, Baillagues, Switzerland) used in a reciprocating motion, and group PT-Rot was prepared with F2 ProTaper files used in a rotation motion. For crack evaluation, half of the samples (n = 30) were embedded in acrylic resin, and the blocks were sectioned at 3, 6, and 9 mm from the apex. The sections were examined under a stereomicroscope and scored for crack presence. The other half of the specimens (n = 30) were obturated using lateral condensation of gutta-percha and AdSeal sealer (Meta Biomed Co, Ltd, Chungbuk, Korea). The specimens were then subjected to a load of 1 mm/min to determine the force required to fracture the roots. WaveOne instruments induced the least amount of cracks and exhibited greatest resistance to fracture compared with ProTaper F2 files whether used in reciprocating or rotating motions. The alloy from which the material is manufactured is a more important factor determining the dentin damaging potential of single-file instruments than the motion of instrumentation.

Collective coordinates theory for discrete soliton ratchets in the sine-Gordon model. A collective coordinate theory is developed for soliton ratchets in the damped discrete sine-Gordon model driven by a biharmonic force. An ansatz with two collective coordinates, namely the center and the width of the soliton, is assumed as an approximated solution of the discrete nonlinear equation. The dynamical equations of these two collective coordinates, obtained by means of the generalized travelling wave method, explain the mechanism underlying the soliton ratchet and capture qualitatively all the main features of this phenomenon. The numerical simulation of these equations accounts for the existence of a nonzero depinning threshold, the nonsinusoidal behavior of the average velocity as a function of the relative phase between the harmonics of the driver, the nonmonotonic dependence of the average velocity on the damping, and the existence of nontransporting regimes beyond the depinning threshold. In particular, it provides a good description of the intriguing and complex pattern of subspaces corresponding to different dynamical regimes in parameter space.

The impacts of a school-wide no smoking strategy and classroom-based smoking prevention curriculum on the smoking behavior of junior high school students. This study aimed at exploring the impacts of a school-wide no smoking strategy and a classroom-based smoking prevention curriculum on smoking-related knowledge, attitude, behavior, and skill of junior high school students. Using a pre-post quasi-experimental design, 469 seventh-to ninth-grade students at four junior high schools in Taiwan, were selected and separated into three groups according to class unit. Experimental group A experienced a school-wide no smoking strategy and a six-session smoking prevention curriculum. Experimental group B experienced only the school-wide no smoking strategy. The control group experienced no intervention. The students were tested 1 week before intervention began and 1 week after it ended. Experimental group A exhibited a better understanding than either experimental group B or the control group of the dangers of smoking and of techniques for refusing cigarettes; and in fact, group A indicated low smoking intention than experimental group B. Experimental group A also had a better attitudes towards resisting smoking than the control group. However, the intervention had no demonstrable effect on the smoking behavior and on the smoking substitution methods of students. To reduce the smoking rates among junior high school students, diversified school-wide no smoking strategies and standardized, diversified instruments should be adopted so that outcomes of smoking prevention work may be assessed more objectively and effectively.