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Tubo-Ovarian Abscesses in Nonsexually Active Adolescent Females: A Large Case Series. The aim of the study was to review the incidence, presentation, and management of tubo-ovarian abscesses (TOA) in nonsexually active (NSA) adolescents. A retrospective chart review was performed at a single children's hospital. We evaluated self-reported NSA females aged < 21 years diagnosed with TOA. Demographics, presenting symptoms, medical history, laboratory studies, imaging, and treatment were reviewed. Sixteen NSA females met inclusion criteria, with one patient presenting with two separate TOAs. Mean age at diagnosis was 14.6 ± 1.8 years; all were menarchal. Presenting symptoms included abdominal pain (88%), fever (76%), and vomiting (53%). Eleven patients (65%) received transabdominal pelvic ultrasound, 2 (12%) had magnetic resonance imaging of pelvis, and 11 (65%) had computed tomography of abdomen/pelvis. All patients had negative gonorrhea and chlamydia testing. Thirteen (76%) had comorbid disease including obstructed hemivagina ipsilateral renal agenesis, active or recent appendicitis, or genitourinary tract anomalies. Sixteen cases underwent drainage via interventional radiology or surgery. Twelve cases (71%) had TOA fluid cultured; five (29%) grew Escherichia coli species. All cases received intravenous antibiotics, and 88% of cases continued outpatient oral antibiotics. Although uncommon in NSA females, patients with underlying comorbidities may be at increased risk for TOA formation. Providers should consider the diagnosis of TOA even in NSA females.

Relationship between in vitro sperm functional tests and in vivo fertility of rams following cervical artificial insemination of ewes with frozen-thawed semen. Several procedures have been proposed to assess structural and functional characteristics of cryopreserved ram semen but none so far have yielded consistent relationships with in vivo fertility. The objectives of this study were to evaluate several sperm function tests as potential markers of in vivo ram fertility (determined by pregnancy rate in ewes) using frozen-thawed semen. In experiment 1, frozen-thawed straws (n=3 per ram) of semen from three high and three low fertility rams were assessed using fluorescent microscopy for (1) progressive motility, (2) viability and, (3) acrosomal status. In experiment 2, frozen-thawed straws (n=3 per ram) of semen from 18 rams of known fertility were analysed using either computer-assisted sperm analysis (CASA) for eight motion characteristics or flow cytometric staining for: (1) viability and acrosomal status, (2) plasma membrane status and capacitation-like changes, and (3) live cells following an osmotic resistance test (ORT). In experiment 3, platelet-activating factor (PAF) was isolated from straws (n=2 per ram) of semen using high-pressure liquid chromatography (HPLC) and quantified using HPLC-tandem mass spectrometry for 18 rams. In experiment 1, no association was found between motility, viability (% live) or acrosomal status (% damaged, % intact and % reacted) and in vivo fertility. In experiment 2, no correlation was found between motility (CASA), viability (% live), acrosomal status (% live, % live intact and % reacted), capacitation status (% capacitated, % non-capacitated), plasma membrane stability (% dead) and % live cells following ORT and ram in vivo fertility. In experiment 3, there was no relationship between PAF content in spermatozoa and ram fertility. In conclusion, we were unable to relate the in vivo fertility of rams with in vitro functional tests of their frozen-thawed semen and suggest that the fertility of a given semen sample cannot easily be quantified using available in vitro tests.

PI3K/AKT/mTOR inhibitors in ovarian cancer. Phisiological activation of PI3K pathway is necessary for cells to regulate many different physiological processes such as transcription, protein synthesis, metabolic responses and membrane trafficking. Abnormal activation of the PI3K pathway leads to an increased activity resulting in tumor onset, maintenance, progression and invasion. Both genetic and epigenetic alterations could affect the normal pathway's activation. Ovarian cancer is the leading cause of death from gynaecological malignancies in the western world. PI3K pathway has been recorded as one of the most deregulated signalling pathway in many tumors, including ovarian ones. So it could be considered an attractive target to be investigated with the various classes of chemical compounds already present or in development. In this rewiew we'll try to discuss the published data of the inhibitors targeting members of the PI3K/ akt/ mTOR pathway in the ovarian cancer setting from a preclinical and clinical point of view, with particular emphasis on drugs combination and strategies of administration. Relevant issues and limitations to the use of particular compounds will be also addressed.

Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia. Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.

Synthesis of honeycomb-like mesoporous pyrite FeS2 microspheres as efficient counter electrode in quantum dots sensitized solar cells. Honeycomb-like mesoporous pyrite FeS2 microspheres, with diameters of 500-800 nm and pore sizes of 25-30 nm, are synthesized by a simple solvothermal approach. The mesoporous FeS2 microspheres are demonstrated to be an outstanding counter electrode (CE) material in quantum dot sensitized solar cells (QDSSCs) for electrocatalyzing polysulfide electrolyte regeneration. The cell using mesoporous FeS2 microspheres as CE shows 86.6% enhancement in power conversion efficiency (PCE) than the cell using traditional noble Pt CE. Furthermore, it also shows 11.4% enhancement in PCE than the cell using solid FeS2 microspheres as CE, due to the mesoporous structure facilitating better contact with polysulfide electrolyte and fast diffusion of redox couple species in electrolyte.

Helicobacter pylori infection increases serum nitrate and nitrite more prominently than serum pepsinogens. Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I : II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori-associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori-induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori-negative and positive volunteers relative to differences in pepsinogens and gastrin. Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti-H. pylori antibody, NOx, gastrin and pepsinogens. In H. pylori antibody-positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori-negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori-positive than negative subjects (p < .001). In subjects with high pepsinogen I : II (6 or higher), serum NOx was higher in H. pylori-positive than in negative subjects. H. pylori-induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori-negative subjects, serum correlates with serum pepsinogen II.

Pulsed Electromagnetic Field Modulates Tendon Cells Response in IL-1β-Conditioned Environment. Strategies aiming at controlling and modulating inflammatory cues may offer therapeutic solutions for improving tendon regeneration. This study aims to investigate the modulatory effect of pulsed electromagnetic field (PEMF) on the inflammatory profile of human tendon-derived cells (hTDCs) after supplementation with interleukin-1β (IL-1β). IL-1β was used to artificially induce inflammatory cues associated with injured tendon environments. The PEMF effect was investigated varying the frequency (5 or 17 Hz), intensity (1.5, 4, or 5 mT), and duty-cycle (10% or 50%) parameters to which IL-1β-treated hTDCs were exposed to. A PEMF actuation with 4 mT, 5 Hz and a 50% duty cycle decreased the production of IL-6 and tumor necrosis factor-α (TNF-α), as well as the expression of TNFα, IL-6, IL-8, COX-2, MMP-1, MMP-2, and MMP-3, while IL-4, IL-10, and TIMP-1 expression increased. These results suggest that PEMF stimulation can modulate hTDCs response in an inflammatory environment holding therapeutic potential for tendon regenerative strategies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:160-172, 2020.

[Characteristics of heterosexual love in alcoholics]. Heterosexual love has many negative impacts on the process of recovery from dependency in a clinical setting; therefore, the present study investigated the characteristics of heterosexual love in alcoholics. Semi-structured interviews were conducted on 23 alcoholics and 14 healthy volunteers in order to ascertain their experiences with heterosexual love, and episodes were compared between the two groups (39 episodes for the alcoholics and 22 episodes for the healthy volunteers). When compared to the healthy volunteers, the length of time from meeting to dating was shorter for the alcoholics, and the measures to deepen relationships were more limited and tended to cause difficulties during the period. In addition, during the period of maintaining relationships, the alcoholics tended to have fewer daily conversations and had more regrets of having started dating. Furthermore, when compared to the healthy volunteers, the mean score for heterosexuality-related satisfaction and the mean score for needing the partner was significantly lower for the alcoholics. These findings suggest that among alcoholics heterosexual love has an element of instability that reflects a lower degree of self-acceptance; therefore, it is necessary to remain aware of this point when providing support.

Multi-scale and multi-domain computational astrophysics. Astronomical phenomena are governed by processes on all spatial and temporal scales, ranging from days to the age of the Universe (13.8 Gyr) as well as from kilometre size up to the size of the Universe. This enormous range in scales is contrived, but as long as there is a physical connection between the smallest and largest scales it is important to be able to resolve them all, and for the study of many astronomical phenomena this governance is present. Although covering all these scales is a challenge for numerical modellers, the most challenging aspect is the equally broad and complex range in physics, and the way in which these processes propagate through all scales. In our recent effort to cover all scales and all relevant physical processes on these scales, we have designed the Astrophysics Multipurpose Software Environment (AMUSE). AMUSE is a Python-based framework with production quality community codes and provides a specialized environment to connect this plethora of solvers to a homogeneous problem-solving environment.

Quality assessment of olive oils based on temperature-ramped HS-GC-IMS and sensory evaluation: Comparison of different processing approaches by LDA, kNN, and SVM. For the first time, this study describes a HS-GC-IMS strategy for analyzing non-targeted volatile organic compounds (VOCs) profiles to distinguish between virgin olive oils of different classification. Correlations among measured flavor characteristics and sensory attributes evaluated by a test panel were determined by applying unsupervised (PCA, HCA) and supervised (LDA, kNN and SVM) chemometric techniques. PCA and HCA were applied for natural clustering of the samples and LDA, kNN, and SVM methods were used to create predictive models for olive oil classification. Identification of 26 target compounds revealed which compounds are responsible for discrimination, and how their distribution correlates with the sensory evaluation. In the investigated samples, LDA, kNN, and SVM models correctly classified 83.3%, 73.8%, and 88.1% of the samples, respectively. This suggests that mathematical correlations of HS-GC-IMS 3D fingerprints with the sensory analysis may be appropriate for calculating a good predictive value to classify virgin olive oils.

Surface ripples cause the large fluid spaces between gel phase bilayers containing small amounts of cholesterol. Previous studies have found that small concentrations of cholesterol, or several other molecules such as benzene and asialoganglioside, dramatically increase the fluid separation between gel phase phosphatidylcholine bilayers. These observations can not be explained in terms of changes in the repulsive and attractive pressures known to exist between flat gel phase bilayer surfaces. We show here that the increase in fluid space occurs as a consequence of cholesterol inducing large periodic ripples in the plane of the bilayer. The analysis of Mortensen et al. (Biochim. Biophys. Acta 945, 221-245) indicates that the sides of the ripples primarily contain gel phase phosphatidylcholine, whereas the apices are enriched in cholesterol and are liquid-crystalline. We argue that the large fluid spaces can be explained by steric repulsion between adjacent bilayers caused both by thermally induced accordion-like motions of these ripples and defects in the ripple organization. In addition, ripples potentially can decrease van der Waals attraction and change hydration repulsion between bilayers.

The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors. High-protein (HP) diets are often advocated for weight reduction and weight loss maintenance. The aim was to compare the effect of low-fat, high-carbohydrate (HC) and low-fat, HP ad libitum diets on weight maintenance after weight loss induced by a very low-calorie diet, and on metabolic and cardiovascular risk factors in healthy obese subjects. Forty-eight subjects completed the study that consisted of an energy restriction period of 5-6 weeks followed by a weight maintenance period of 12 weeks. During weight maintenance subjects received maltodextrin (HC group) or protein (HP group) (casein (HPC subgroup) or whey (HPW subgroup)) supplements (2 x 25 g per day), respectively and consumed a low-fat diet. Subjects in the HP diet group showed significantly better weight maintenance after weight loss (2.3 kg difference, P=0.04) and fat mass reduction (2.2 kg difference, P=0.02) than subjects in the HC group. Triglyceride (0.6 mM difference, P=0.01) and glucagon (9.6 pg ml(-1) difference, P=0.02) concentrations increased more in the HC diet group, while glucose (0.3 mM difference, P=0.02) concentration increased more in the HP diet group. Changes in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, insulin, HOMAir index, HbA1c, leptin and adiponectin concentrations did not differ between the diets. No differences were found between the casein- or whey-supplemented HP groups. These results show that low-fat, high-casein or whey protein weight maintenance diets are more effective for weight control than low-fat, HC diets and do not adversely affect metabolic and cardiovascular risk factors in weight-reduced moderately obese subjects without metabolic or cardiovascular complications.

[Streptococcal infection and chronic glomerulonephritis in children]. Microbiological, immunological and immunohistochemical studies were carried out in 78 children with different clinicomorphological forms of chronic glomerulonephritis (GN). According to the data obtained, the role of streptococcal infection (SI) is inconclusive in certain clinicomorphological forms of chronic GN, suggesting different approaches to the treatment of these patients. The etiological role of SI is most probable in mesangioproliferative and mesangiocapillary GN, manifesting by hematuric and mixed forms of chronic GN. Antibacterial therapy is indicated to patients with a rise of the level of ASL-O and with the clinical signs of acute SI or exacerbation of chronic tonsillitis in the same patients, especially during immunosuppressive therapy.

Movement of the esophagus during left atrial catheter ablation for atrial fibrillation. The aim of this study was to describe the extent of esophageal mobility that occurs during catheter ablation for atrial fibrillation under conscious sedation. Ablation along the posterior left atrium may cause an atrioesophageal fistula. One strategy for avoiding this risk is to not deliver radiofrequency energy at sites in contact with the esophagus. In 51 consecutive patients with atrial fibrillation who underwent left atrial ablation under conscious sedation, digital cine-fluoroscopic imaging of the esophagus was performed in two views after ingestion of barium paste at the beginning and end of the ablation procedure. Movement of the esophagus was determined at the superior, mid-, and inferior parts of the posterior left atrium in reference to the spine. Mean esophageal movement was 2.0 +/- 0.8 cm (range = 0.3 to 3.8 cm) at the superior, 1.7 +/- 0.8 cm (range = 0.1 to 3.5 cm) at the mid-, and 2.1 +/- 1.2 cm (range = 0.1 to 4.5 cm) at the inferior levels. In 67% of the 51 patients, the esophagus shifted by > or =2 cm, and in 4% there was > or =4 cm of lateral movement. The mean change in esophageal luminal width was 5 +/- 7 mm (range = 0 to 36 mm) at the superior, 5 +/- 7 mm (range = 0 to 32 mm) at the mid-, and 6 +/- 7 mm (range = 0 to 21 mm) at the inferior levels of the posterior left atrium. The esophagus often is mobile and shifts sideways by > or=2 cm in a majority of patients undergoing catheter ablation for atrial fibrillation under conscious sedation. Therefore, real-time imaging of the esophagus may be helpful in reducing the risk of esophageal injury during radiofrequency ablation along the posterior left atrium.

Genetically crosslinked hemoglobin: a structural study. The crystal structures of three recombinant human hemoglobins, rHb1. 0, rHb1.1 and rHb1.2, have been determined in the deoxy state at 1.8 A resolution. Two of the three proteins, rHb1.1 and rHb1.2, contain a genetic fusion of the alpha subunits, a one- or two-glycine link, respectively, whereas rHb1.0 does not. The glycine crosslinks, localized between one N- and C--termini pair of the alpha subunits in the deoxy crystalline state, do not perturb the overall tertiary or quaternary or even the local structure of hemoglobin. Therefore, genetic fusion to prevent the dissociation of the hemoglobin tetramer, thereby inhibiting renal clearance based upon molecular size, is a structurally conservative method to stabilize hemoglobin for use as an oxygen-delivery therapeutic.

[Dependence of the redistribution of ligand-receptor complexes in cultured cells on the type of growth and on the cell cycle phase]. The process of active redistribution of ligand-receptor complexes on the surface of both suspension (LS) and adapted for growing in monolayer (LMS) sublines of mouse fibroblasts L was studied. The binding of ligands to its specific receptors on the surface of the LS cells induced an accumulation of ligand-receptor complexes on one pole of a cell with the formation of a typical cap. Under the same conditions in the LSM cells the cleaning of processes and lamello-plasma surfaces from the ligand-receptor complexes was registered. The binding of ligands to the surface of the LSM cells, detached with EDTA, induced the same capping process, as in the case of the LS cells. No differences were found in the redistribution capacity of the ligand-receptor complexes in synchronized cultures of the LS and LSM cells in the G1 and S phase of the cycle. But such a redistribution was not registered on the surface of cells in metaphase and anaphase. The accumulation of ligand-receptor complexes was found in the region of cleavage between daughter cells in telophase. These results are in a good agreement with the well-known data on the changes in the cytoskeleton organization during transition from a monolayer to a suspension state and during mitosis.

Analytical study of the clinical response to two distinct adoptive immunotherapies for advanced hepatocellular carcinoma: comparison between LAK cell and CTL therapy. To evaluate the effect of two distinct adoptive immunotherapies, tumor-specific cytotoxic T-cell (CTL) therapy and lymphokine-activated killer (LAK) cell therapy, the clinical responses of patients with stage IV primary hepatocellular carcinoma (HCC) treated with these therapies were studied. Of 18 patients treated with CTL, 3 had complete regression (CR), 2 had partial regression, and 3 had minor regression (MR). Their median survival was 21 months after the end of therapy, and 1 CR patient survived for > 6 years. On the other hand, in the LAK-cell-treated group of eight patients, four had MR and their median survival was only 2 months. No survival was observed 27 months after the end of LAK cell therapy. These results indicate that tumor-specific CTL therapy is more effective than LAK cell therapy and that it might be a promising therapeutic tool for advanced HCC patients.

New therapeutic opportunities for 5-HT2 receptor ligands. Serotonergic dysfunction is mainly associated with neuropsychiatric and cardiovascular disorders but has also been linked with many other pathological conditions. Serotonin (5-hydroxytryptamine, 5-HT) mediates numerous physiological functions in the brain and the periphery by activating a variety of receptors. 5-HT receptors are divided into four classes, three of which belong to the G protein-coupled receptor family. This review provides an overview of the recent pharmacological developments involving the Gq-coupled 5-HT2 receptor subfamily as well as the pathological implications of this receptor subfamily with regard to fibrosis, the central nervous system, cardiovascular disorders, and cancer. The final section highlights new therapeutic opportunities and emerging research revealing unexplored medical opportunities for this class of 5-HT receptors. The development of biased 5-HT2 receptor ligands appears to be an interesting topic in various areas. In light of recent discoveries, the need for the development of new and safer drugs should take into account the risk of cardiovascular side effects such as pulmonary hypertension and heart valve disease.

Developmental and behavioural outcome in obstetric brachial plexus palsy. Forty-four children with obstetric brachial plexus palsy were assessed for both developmental attainment and behavioural problems. Analysis of the resulting data revealed developmental and behavioural problems previously not identified, particularly in those with more severe injuries. These effects were independent of the general condition of the child at birth, as indicated by their Apgar scores. Further studies are required to provide clarification of these children's difficulties, the mechanisms by which they occur and effective strategies to address them.

Long-term pain relief produced by intrathecal morphine infusion in 53 patients. The present report details the characteristics of the analgesic effects of morphine administered chronically by infusion pumps implanted in 53 patients suffering from terminal metastatic disease. The median postimplant survival time in these patients was 4 months. Patients (mean age 58 years) were characterized according to the duration of pain before pump implantation (mean 16 months), prior consumption of systemic opioids (mean one to six daily analgesic equivalents of morphine), and their response to a trial intrathecal dose of morphine (1 to 2 mg). The median infusion dose at 2 weeks was 3.8 mg/day. The analgesic index, calculated as (quality of pain relief x duration of pain relief in hours)/morphine dose in mg, that was observed after the trial dose of morphine was determined for each patient. A close correlation was observed between the acute (2-week) infusion dose necessary to produce pain relief and the analgesic index such that the infusion dose = -8.0 x log (analgesic index) + 17.1. By 16 weeks, the mean spinal morphine dose for the group had increased by a factor of about 2.5; however, significant variation in the dose incrementation was documented. The maximum increase was observed in patients with a low analgesic index, and this rapid incrementation was usually correlated with an unsatisfactory overall outcome. Evidence that long-term infusion continues to yield analgesia was evidenced in six cases where there was an unanticipated loss of drug infusion and a corresponding increase in parenteral narcotic consumption. These data indicate the long-term efficacy and safety of spinal opioid infusion in patients with terminal cancer, and emphasize the advantage of assessing the sensitivity of the patient to spinal opioids by a standardized trial injection prior to pump placement as a prognostic indication of outcome.

Preparation of collagen-based materials for wound dressing. To describe the methods which were used to develop collagen-based materials for wound dressing. Fresh frozen bovine tendon was treated with 0.05 mol/L acetic acid at pH 3.2 for 48-72 hours, homogenized, filtered, mixed with 8% chondroitin sulphate, for creating a deaerated 1.5%-2.5% collagen solution. The solution was lyophilized in either a pre-frozen or non-pre-frozen mould. The collagen sponge was then cross-linked with 0.25% glutaraldehyde for 24 hours. Three other types of wound dressings were developed using a similar method: collagen membrane with a polyurethane membrane onlay, polyurethane-coated collagen membrane and collagen membrane on gauze. It was demonstrated that the use of frozen bovine tendon was stable, and that the prepared collagen sponge contained pores of 50-400 microm in diameter. Collagen could be used as wound dressing.

[Postoperative changes in serum levels of iron, transferrin and ferritin in surgical patients]. The association of serum levels of iron, transferrin and ferritin with surgical trauma has been analyzed in 21 surgical patients. The apparent decline of serum iron concentration was seen in the early stage of postoperative period, which was significantly manifest among the patients with major surgical process, such as pancreatectomy and hepatectomy etc. And there was no relationship between serum levels of iron and volumes of bleeding during operation and/or volumes of blood transfusion. Similarly, serum transferrin concentration decreased. On the other hand, serum ferritin concentration elevated after operation. These factors gradually returned to the preoperative levels with recovery from surgical injury. The transferrin decline in serum concentration was thought to be due to a change as rapid turnover protein. However, the decline of serum iron concentration and the elevation of serum ferritin concentration might be associated with cellular proliferative activity to repair operative injury. These results suggest that the condition of iron metabolism in management of surgical patients should be important.

Effect of sevelamer hydrochloride on markers of bone turnover in Japanese dialysis patients with low biointact PTH levels. In hemodialysis patients, adynamic bone disease has been reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus. Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31+/-18 pg/mL to 95+/-96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients. Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes.

In vitro evolution used to define a protein recognition site within a large RNA domain. A minimum of 460 nucleotides of 16S ribosomal RNA are needed to fold the target site for E. coli ribosomal protein S4, although a much smaller region within this large domain is protected from chemical reagents by the protein. Starting with a 531-nucleotide tRNA fragment, cycles of mutagenesis, selection with S4, and amplification ('in vitro evolution') were used to obtain a pool of 30 RNA sequences selected for S4 recognition but approximately 30% different from wild type. Numerous compensatory base pair changes have largely preserved the same secondary structure among these RNAs as found in wild-type sequences. A 20-base deletion and a single nucleotide insertion are among several unusual features found in most of the selected sequences and also prevalent among other prokaryotic rRNAs. Most of the compensatory base changes and selected features are located outside of the region protected by S4 from chemical reagents. It was unexpected that S4 would select for RNA structures throughout such a large domain; the selected features are probably contributing indirectly to S4 recognition by promoting correct tertiary folding of the region actually contacted by S4. The role of S4 may be to stabilize this domain (nearly one-third of the 16S rRNA) in its proper conformation for ribosome function.

Sarcomeric myopathies associated with tremor: new insights and perspectives. Myopathies are a large and heterogeneous group of disorders associated with mutations in structural and regulatory genes responsible for proper muscle assembly, organization and function. Despite the molecular diversity of inherited myopathies, they have historically been classified by the phenotypic traits observed in affected patients. It is therefore common for myopathies originating from mutations in different genes to be grouped together due to similar physical manifestations, and conversely myopathies resulting from mutations in the same gene to be considered separately due to disparate symptoms. Herein, we focus on an early onset myopathy linked to inherited or de novo mutations in sarcomeric genes that is characterized by muscle weakness, hypotonia and tremor, and further highlight that it may constitute a new form of myopathy, with tremor as its defining feature. Based on recent reports, we also discuss the possible myogenic origin of the tremor that may start at the level of the sarcomere due to structural and/or contractile alterations occurring as a result of the identified mutations. It is our hope that establishment of this form of myopathy accompanied by myogenic tremor as a new disease entity will have important diagnostic and therapeutic implications.

Stability and structure of protein-lipoamino acid colloidal particles: toward nasal delivery of pharmaceutically active proteins. To circumvent the painful intravenous injection of proteins in the treatment of children with growth deficiency, anemia, and calcium insufficiency, we investigated the stability and structure of protein-lipoamino acid complexes that could be nasally sprayed. Preparations that ensure a colloidal and structural stability of recombinant human growth hormone (rhGH), recombinant human erythropoietin (rhEPO), and salmon calcitonin (sCT) mixed with lauroyl proline (LP) were established. Protein structure was controlled by circular dichroism, and very small sizes of ca. 5 nm were determined by dynamic light scattering. The colloidal preparations could be sprayed with a droplet size of 20-30 μm. The molecular structure of aggregates was investigated by all-atom molecular dynamics. Whereas a lauroyl proline capping of globular proteins rhGH and rhEPO with preservation of their active structure was observed, a mixed micelle of sCT and lipoamino acids was formed. In the latter, aggregated LP constitutes the inner core and the surface is covered with calcitonins that acquire a marked α-helix character. Hydrophobic/philic interaction balance between proteins and LP drives the particles' stability. Passage through nasal cells grown at confluence was markedly increased by the colloidal preparations and could reach a 20 times increase in the case of EPO. Biological implications of such colloidal preparations are discussed in terms of furtiveness.

First detection of the staphylococcal trimethoprim resistance gene dfrK and the dfrK-carrying transposon Tn559 in enterococci. The trimethoprim resistance gene dfrK has been recently described in Staphylococcus aureus, but so far has not been found in other bacteria. A total of 166 enterococci of different species (E. faecium, E. faecalis, E. hirae, E. durans, E. gallinarum, and E. casseliflavus) and origins (food, clinical diseases in humans, healthy humans or animals, and sewage) were studied for their susceptibility to trimethoprim as determined by agar dilution (European Committee on Antimicrobial Susceptibility Testing) and the presence of (a) the dfrK gene and its genetic environment and (b) other dfr genes. The dfrK gene was detected in 49% of the enterococci (64% and 42% of isolates with minimum inhibitory concentrations of ≥2 mg/L or ≤1 mg/L, respectively). The tet(L)-dfrK linkage was detected in 21% of dfrK-positive enterococci. The chromosomal location of the dfrK gene was identified in one E. faecium isolate in which the dfrK was not linked to tet(L) gene but was part of a Tn559 element, which was integrated in the chromosomal radC gene. This Tn559 element was also found in 14 additional isolates. All combinations of dfr genes were detected among the isolates tested (dfrK, dfrG, dfrF, dfrK+dfrG, dfrK+dfrF, dfrF+dfrG, and dfrF+dfrG+dfrK). The gene dfrK gene was found together with other dfr genes in 58% of the tested enterococci. This study suggested an exchange of the trimethoprim resistance gene dfrK between enterococci and staphylococci, as previously observed for the trimethoprim resistance gene dfrG.

Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton? Osteoporosis is a major, and increasing, public health problem. In this review we examine the evidence that childhood physical activity is an important determinant of bone mineral in adult years, and as such, may help to prevent osteoporosis. Animal studies provide incontrovertible evidence that growing bone has a greater capacity to add new bone to the skeleton than does adult bone. Observational studies in children undertaking routine physical activity and cross-sectional athlete studies in young sportspeople both reveal that activity is positively associated with bone mineral density (BMD). Longitudinal studies in pre- and peripubertal gymnasts reveal BMD gains far in excess of those that can be achieved in adulthood. However, such studies permit only limited conclusions as they contain the potential for selection bias and can be confounded by other determinants of bone mineral (e.g. dietary and lifestyle factors). Thus, research comparing inter-individual playing-to-nonplaying arm differences in bone mineral (e.g., in racquet sports) have proven to be extremely useful. These studies suggest that the BMD differences are clearly greater when bone is subjected to mechanical loading prior to the end of puberty and longitudinal growth of the body (in women, before menarche) rather than after it. Tanner stage II and III appears to be the maturational stage when the association between exercise and BMD becomes manifest in most adolescents. Do conclusions drawn from athlete studies apply to the general population? Randomised intervention studies of physical activity and bone mineral accrual in normal children confirm that childhood activity is strongly associated with bone mineral accrual. Furthermore, some retired athlete studies and a detraining study suggest that adolescent bone gain may, at least partly, persist despite reduced adult physical activity. Mechanisms that may underlie the association between childhood physical activity and bone mineral accrual are outlined. Thus, it appears that physical activity during the most active period of maturity (with respect to longitudinal growth of the body) plays a vital role in optimising peak bone mass and that benefits may extend into adulthood.

Double-negative feedback loop between microRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis. Growing evidence indicates that the aberrant expression of microRNAs (miRNAs) contributes to tumor development; however, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. In this study, we report that microRNA-422a (miR-422a) is significantly down-regulated in HCC tumor samples and cell lines compared with normal controls, and its expression level is negatively correlated with pathological grading, recurrence, and metastasis. The restoration of miR-422a expression in HCC tumor cells significantly inhibited cell proliferation and migration in vitro. At the same time, the overexpression of miR-422a in HCC tumor cells significantly inhibits tumor growth and liver metastasis in xenograft tumor models. A mechanistic study identified three genes, forkhead box G1 (FOXG1), FOXQ1, and FOXE1, as miR-422a targets in the regulation of HCC development. We also investigated the function of the three targets themselves in HCC tumorigenesis using RNAi manipulation and demonstrated that the knockdown of these targets led to significant inhibition of tumor cell proliferation and migration both in vitro and in vivo. More interestingly, a potential miR-422a promoter region was identified. Both the promoter activity and miR-422a expression were negatively regulated by the three targets, indicating that a double-negative feedback loop exists between miR-422a and its targets. Moreover, we explored the therapeutic potential of miR-422a in HCC treatment and found that the therapeutic delivery of miR-422a significantly inhibited tumor development in a xenograft tumor model and a diethylnitrosamine-induced primary HCC model. Our findings show the critical roles of miR-422a and its targets--FOXG1, FOXQ1, and FOXE1--in the regulation of HCC development and provide new potential candidates for HCC therapy.

Developing an evidence-based practice protocol: implications for midwifery practice. Evidence-based practice is defined and its importance to midwifery practice is presented. Guidelines are provided for the development of an evidence-based practice protocol. These include: identifying the clinical question, obtaining the evidence, evaluating the validity and importance of the evidence, synthesizing the evidence and applying it to the development of a protocol or clinical algorithm, and, finally, developing an evaluation plan or measurement strategy to see if the new protocol is effective.

Positive correlation between mammalian life span and cellular resistance to stress. Identifying the mechanisms determining species-specific life spans is a central challenge in understanding the biology of aging. Cellular stresses produce damage, that may accumulate and cause aging. Evolution theory predicts that long-lived species secure their longevity through investment in a more durable soma, including enhanced cellular resistance to stress. To investigate whether cells from long-lived species have better mechanisms to cope with oxidative and non-oxidative stress, we compared cellular resistance of primary skin fibroblasts from eight mammalian species with a range of life spans. Cell survival was measured by the thymidine incorporation assay following stresses induced by paraquat, hydrogen peroxide, tert-butyl hydroperoxide, sodium arsenite and alkaline pH (sodium hydroxide). Significant positive correlations between cell LD90 and maximum life span were found for all these stresses. Similar results were obtained when cell survival was measured by the MTT assay, and when lymphocytes from different species were compared. Cellular resistance to a variety of oxidative and non-oxidative stresses was positively correlated with mammalian longevity. Our results support the concept that the gene network regulating the cellular response to stress is functionally important in aging and longevity.

A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA-DR, while smoking is an important environmental risk factor. We studied a potential gene-environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)-seropositive and RF-seronegative disease. A population-based case-control study involving incident cases of RF-seropositive and RF-seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA-DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes. The relative risk of RF-seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF-seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95% CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF-seronegative RA. The disease risk of RF-seropositive RA associated with one of the classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.

Impaired fasting glucose and outcomes of ST-elevation acute coronary syndrome treated with primary percutaneous intervention among patients without previously known diabetes mellitus. Fasting blood glucose levels (FG) are related to adverse outcomes in all patients with acute myocardial infarction (AMI), probably more so than admission glucose (AG) levels. We sought to examine this correlation among patients with ST-elevation AMI treated with primary percutaneous coronary interventions (PPCI). Our cohort included 570 consecutive patients without previously known diabetes mellitus who were treated with PPCI for ST-elevation AMI. The cohort was divided according to FG levels measured on days 2 to 4 of hospitalization, while the patients were clinically stable: FG < or = 100 mg/dL, normal range; FG 100-110 mg/dL, mildly impaired FG; FG 110-126 mg/dL, significantly impaired FG; FG > or = 126 mg/dL, diabetic range. One third of the cohort had impaired FG, of whom 20% had FG levels in the diabetic range. There was a weak correlation between AG and FG levels (r = 0.38, P = .000). In the multivariate analysis, adjusted for AG quartiles, patients with FG > or = 110 mg/dL were more likely to die within 30 days (odds ratio 1.7, 95% CI 1.03-2.70, P = .04). Admission glucose levels did not independently impact on 30-day mortality (odds ratio 0.99, 95% CI 0.50-1.90, P = .96). Fasting blood glucose levels may be routinely assessed among patients with ST-elevation AMI undergoing PPCI, possibly aiding in risk prognostication and the tailoring of therapy.

Can a functional postural exercise improve performance in the cranio-cervical flexion test?--a preliminary study. Deep cervical flexor (DCF) muscle impairment is common in patients with neck pain. Retraining function is often commenced with a motor relearning approach, requiring the patient to practice and hold a cranio-cervical flexion position in supine lying. Motor relearning requires multiple repetitions which is difficult to achieve if only exercising in supine. This preliminary study investigated the effects of training the DCF with a functional exercise: assumption of an upright lumbo-pelvic and spinal postural position, adding a neck lengthening manoeuvre. The exercise effect was evaluated by changes in sternocleidomastoid (SCM) muscle activity in the cranio-cervical flexion test (CCFT). Twenty subjects with neck pain were randomly assigned to an exercise or control group. The exercise group trained for two weeks. Pre and post-intervention, electromyographic (EMG) signals were recorded from the SCM muscles during the five stages of the CCFT. Results indicated that the exercise improved performance. SCM EMG signal amplitudes decreased across all CCFT stages, albeit significant only at the first and third stages of the test; 22 mmHg (p = 0.043) and 26 mmHg (p = 0.003). No differences were evident in the control group (all p > 0.05). There was no difference between groups for pain and disability measures. This initial study indicates that a postural exercise, convenient to perform during the working day, improves the pattern of SCM muscle activity in the CCFT. Whilst further research is necessary, these observations suggest the worth of such an exercise to augment other training in the rehabilitation of patients with neck pain.

Cost containment, solidarity and cautious experimentation: Swedish dilemmas. This paper uses secondary data analysis and a literature review to explore a "Swedish Dilemma": Can Sweden continue to provide a high level of comprehensive health services for all regardless of ability to pay--a policy emphasizing "solidarity"--or must it decide to impose increasing constraints on health services spending and service delivery--a policy emphasizing "cost containment?" It examines recent policies and longer term trends including: changes in health personnel and facilities; integration of health and social services for older persons; introduction of competition among providers; cost sharing for patients; dismantling of dental insurance; decentralization of government responsibility; priority settings for treatment; and encouragement of the private sector. It is apparent that the Swedes have had considerable success in attaining cost containment--not primarily through "market mechanisms" but through government budget controls and service reduction. Further, it appears that equal access to care, or solidarity, may be adversely affected by some of the system changes.

Esthetic restoration of infra-occluded retained primary mandibular incisors with all-ceramic crowns in adult dentition. The prevalence of hypodontia is reported to be between 1.5% to 10% in the permanent dentition. In the anterior teeth, maxillary lateral incisors and mandibular central incisors are the most frequently involved teeth. This causes esthetic problems for the patient. Several reports have focused on restoration of retained maxillary primary anterior teeth, but none have described restoration of retained mandibular primary incisors. This clinical report describes the restoration of infra-occluded retained primary mandibular central incisors of a 17 year-old girl diagnosed with hypodontia. All-ceramic crowns made with computer-aided design/ computer-aided manufacturing technology were used to restore the teeth incisally and interproximally. Due to a relatively short root length and inadequate crown-root ratio, the primary mandibular central incisors were splinted and adjusted to distribute the protrusive force evenly across the maxillary and mandibular incisors. Functional and esthetic results were achieved.

Performance of screening mammography among women with and without a first-degree relative with breast cancer. Although it is recommended that women with a family history of breast cancer begin screening mammography at a younger age than average-risk women, few studies have evaluated the performance of mammography in this group. To compare the performance of screening mammography in women with a first-degree family history of breast cancer and women of similar age without such history. Cross-sectional. Mammography registries in California (n = 1), New Hampshire (n = 1), New Mexico (n = 1), Vermont (n = 1), Washington State n = 2), and Colorado (n = 1). 389 533 women 30 to 69 years of age who were referred for screening mammography from April 1985 to November 1997. Risk factors for breast cancer; results of first screening examination captured for a woman by a registry; and any invasive cancer or ductal carcinoma in situ identified by linkage to a pathology database, the Surveillance, Epidemiology, and End Results program, or a state tumor registry. The number of cancer cases per 1000 examinations increased with age and was higher in women with a family history of breast cancer than in those without (3.2 vs. 1.6 for ages 30 to 39 years, 4.7 vs. 2.7 for ages 40 to 49 years, 6.6 vs. 4.6 for ages 50 to 59 years, and 9.3 vs. 6.9 for ages 60 to 69 years). The sensitivity of mammography increased significantly with age (P = 0.001 [chi-square test for trend]) in women with a family history and in those without (63.2% [95% CI, 41. 5% to 84.8%] vs. 69.5% [CI, 57.7% to 81.2%] for ages 30 to 39 years, 70.2% [CI, 61.0% to 79.5%] vs. 77.5% [CI, 73.3% to 81.8%] for ages 40 to 49 years, 81.3% [CI, 73.3% to 89.3%] vs. 80.2% [CI, 76.5% to 83.9%] for ages 50 to 59 years, and 83.8% [CI, 76.8% to 90.9%] vs. 87.7% [CI, 84.8% to 90.7%] for ages 60 to 69 years). Sensitivity was similar for each decade of age regardless of family history. The positive predictive value of mammography was higher in women with a family history than in those without (3.7% vs. 2.9%; P = 0.001). Cancer detection rates in women who had a first-degree relative with a history of breast cancer were similar to those in women a decade older without such a history. The sensitivity of screening mammography was influenced primarily by age.

Review article: is ultrasound guidance advantageous for interventional pain management? A systematic review of chronic pain outcomes. Modern ultrasound (US) is an attractive alternative to anatomical landmark-, nerve stimulation-, and fluoroscopic-guided techniques for interventional procedures performed to treat chronic pain syndromes. In this review, we evaluated the effects of US guidance compared with traditional guidance techniques on performance, efficacy, and safety outcomes for interventional chronic pain procedures. We identified 46 studies, including 41 case series and 5 randomized trials of intermediate-to-good quality that investigated the use of US guidance for a diverse variety of chronic pain procedures. Our results suggest that US guidance can match or improve performance- and safety-related outcomes compared with many anatomic landmark-, nerve stimulation-, and fluoroscopic-guided techniques for treating chronic pain. There are presently insufficient data to support improved efficacy with procedures performed with US guidance for relieving both short- and long-term chronic pain.

Molecular characterization of Borna disease virus from naturally infected animals and possible links to human disorders. In this review data are presented which indicate a high degree of genetic stability of BDV in his natural host, the horse. Despite this high degree of sequence conservation, variation in antigenicity was found, which did not influence the pathogenic properties of the virus. In addition, the correlation between BDV-seropositivity and a variety of psychiatric and neurological disorders in humans is discussed. In diagnostically unselected psychiatric patients we found a similar distribution of psychiatric disorders in BDV seropositives compared to seronegatives. Investigations of cerebrospinal fluid revealed cases of BDV encephalitis in BDV seropositive psychiatric and neurological patients. In contrast to others, we have found no evidence for the presence of BDV-RNA or BDV in human peripheral blood leucocytes.

Acute asthma: under attack. The burden of asthma (death, disability, and an increasing prevalence) makes it a major public health problem worldwide. In an effort to decrease this burden, investigators are studying many aspects of this disease. The role of race, ethnicity, infections, and pollutants as triggers, as well as the risk factors are now being defined. Research into methods to decrease acute exacerbations and improve emergency and in-hospital management, using standardized protocols and incentives for follow-up care, has yielded valuable information but has met with limited success. Adherence to the national guidelines has been poor and to some extent can be attributed to the lack of a practical method of measuring the degree of lung inflammation and cumbersome treatment protocols. Exhaled nitric oxide is a noninvasive marker of inflammation and may provide a rational method to titrate corticosteroid and leukotriene receptor antagonist therapy. The best route and dosing regimen for corticosteroid administration (oral vs intramuscular vs nebulized) are the subject of several studies, with no clear-cut winner. The burden of asthma in developing countries with limited financial resources has also triggered a search for simpler, cheaper, and practical methods for beta-agonist delivery using indigenous spacers. Recent research in asthma has unveiled our incomplete knowledge of the disease but has also provided a sense of where efforts should be expended. Research into the genetics and pharmacogenetics of asthma and into the societal factors limiting the delivery of optimal care is likely to yield useful and practical information.

The gel test: sensitivity and specificity for unexpected antibodies to blood group antigens. The recently FDA-licensed anti-IgG gel test for pretransfusion antibody detection requires crossover validation before implementation. Six hundred coded samples sent for routine pretransfusion tests were used to compare GEL (ID-MTS, Ortho Diagnostic Systems Inc., Raritan, NJ) with Löw and Messeter's low-ionic-strength saline (LISS). There were 456 GEL-LISS-, 97 GEL+LISS+, 45 GEL-LISS+, and 2 GEL+LISS- tests. The 144 positive tests involved 157 antibodies; 67 of these (cold auto, anti-M, -Le, etc.) were considered harmless with respect to transfusion management. GEL-LISS+ tests included seven samples containing potentially significant antibodies (assumed from specificity): anti-K(4), -Jka, -Fyb, and -S. Two potentially significant antibodies (anti- C and -D) were GEL+LISS-. Sensitivity and specificity for potentially significant antibodies were 92% and 96% for GEL, and 98% and 90% for LISS, respectively. The seven GEL-LISS+ samples associated with potentially significant antibodies were from six patients. Five of these antibodies, all detected in immune-suppressed patients, reacted predominantly as agglutinins in LISS. None of these seven antibodies were detected reliably by polyethylene glycol and LISS-additive tube methods. In light of the immune status of the patients with GEL-LISS+ agglutinins with specificity normally considered potentially significant, and because other valid methods did not detect these antibodies, their clinical importance is questionable. Excluding these questionable antibodies, GEL has the same sensitivity and better specificity than LISS. GEL is a valid method for pretransfusion antibody detection.

Suppression of photorefractive beam fanning using achromatic gratings. We show that achromatic grating techniques, using the 488- and 514.5-nm lines of the argon-ion laser, can suppress beam fanning while still allowing two-beam coupling to occur. The suppression is studied as a function of the ratio of the two colors used to form the achromatic grating.

The future of the US endangered species act. The United States Endangered Species Act of J973 (ESA) is the strongest tool for protecting plants and animals in the US and has served as a model of species protection for many other nations. Because the goals of the Act - to conserve all endangered and threatened species in the US and the ecosystems upon which they depend - are widely supported among US environmentalists and biologists, it is commonly believed that these groups offer united support for the legislation. Within the US, however, vigorous debate ensues among conservation biologists as to the effectiveness of the species-oriented approach of the Act.

Coisolation of glutathione peroxidase, catalase and superoxide dismutase from human erythrocytes. Glutathione peroxidase (GSH-Px; glutathione: hydrogen peroxide oxidoreductase; EC 1.11.1.9), catalase (H2O2: H2O2 oxidoreductase; EC 1.11.1.6) and superoxide dismutase (superoxide: superoxide oxidoreductase; EC 1.15.1.1) were coisolated from human erythrocyte lysate by chromatography on DEAE-cellulose. Glutathione peroxidase was separated from superoxide dismutase and catalase by thiol-disulfide exchange chromatography and then purified to approximately 90% homogeneity by gel permeation chromatography and dye-ligand affinity chromatography. Catalase and superoxide dismutase were separated from each other and purified further by gel permeation chromatography. Catalase was then purified to approximately 90% homogeneity by ammonium sulfate precipitation and superoxide dismutase was purified to apparent homogeneity by hydrophobic interaction chromatography. The results for glutathione peroxidase represent an improvement of approximately 10-fold in yield and 3-fold in specific activity compared with the established method for the purification of this enzyme. The yields for superoxide dismutase and catalase were high (45 mg and 232 mg, respectively, from 820 ml of washed packed cells), and the specific activities of both enzymes were comparable to values found in the literature.

Perception of depth from shading in infant chimpanzees ( Pan troglodytes). We investigated the ability to perceive depth from shading, one of the pictorial depth cues, in three chimpanzee infants aged 4-10 months old, using a preferential reaching task commonly used to study pictorial depth perception in human infants. The chimpanzee infants reached significantly more to three-dimensional toys than to pictures thereof and more to the three-dimensional convex than to the concave. Furthermore, two of the three infants reached significantly more to the photographic convex than to the photographic concave. These infants also looked longer at the photographic convex than the concave. Our results suggest that chimpanzees perceive, at least as early as the latter half of the first year of life, pictorial depth defined by shading information. Photographic convexes contain richer information about pictorial depth (e.g., attached shadow, cast shadow, highlighted area, and global difference in brightness) than simple computer-graphic graded patterns. These cues together might facilitate the infants' perception of depth from shading.

Effects of cuminaldehyde on melanoma cells. Cuminaldehyde (4-isopropylbenzaldehyde) suppressed melanin formation in cultured murine B16-F10 melanoma cells in a dose-dependent decrease up to 0.25 mm without affecting cell growth. Approximately 30% suppression in melanin production resulted when the cells were cultured with 0.25 mm of cuminaldehyde. This activity was not noticeable with cultured human A375 melanoma cells.

ATPase activity and ATP-dependent proton translocation in plasma membrane vesicles of turtle bladder epithelial cells. ATP-induced quenching of fluorescence of acridine orange (a pH probe) or Oxonol V (a potential difference probe) is evoked in turtle bladder membrane vesicles in suspending media of appropriate ionic composition and is insensitive to oligomycin, valinomycin, and ouabain. These effects are ascribed to a membrane-bound, ouabain-resistant ATPase which mediates an active electrogenic proton transport.

Contemporary management and outcome of myelomeningocele: the Rotterdam experience. Myelomeningocele (MMC) is the most common form of spina bifida, with a lifelong impact on the quality of life for infants born with this condition. In recent decades, fetal surgery has evolved from an experimental therapy to standard of care for many centers in the world. In this study, the authors aimed to provide an overview of the current management and outcomes for infants with MMC managed at their institution. This then provides a center-specific historical cohort for comparison with future antenatal-treated MMC cases. This is a retrospective, single-institution cohort study including all consecutive MMC cases between January 1, 2000, and June 1, 2018, at Erasmus MC. Outcome data included closure of the defect (location, timing, and surgical parameters), hydrocephalus management, Chiari malformation type II (CMTII) management, incidence of spinal cord tethering and outcome, motor outcomes, and continence. A total of 93 patients were included with predominantly lumbosacral lesions. Two patients died during follow-up. Hydrocephalus was present in 84%, with a 71% ventriculoperitoneal shunt reoperation rate. Surgery was performed in 12% for a tethered spinal cord at a mean age of 8 years. Decompression surgery was performed in 3 patients for CMTII. Special education in 63% was significantly associated with hydrocephalus (p < 0.015). Nineteen percent of patients were able to walk independently, and 47% were nonambulators. Social continence for urine was obtained in 75% of patients, 4% had fecal incontinence. This study provides an overview of current MMC outcomes at the authors' center and will serve as a historical cohort for comparison with future fetal surgery cases operated on at the center in the coming years. Apart from a relatively low surgical untethering rate, the authors' outcome data are comparable to those in the literature. Hydrocephalus is highly prevalent in postnatally treated MMC patients; in this study as in much of the literature, hydrocephalus is correlated with a low cognitive function. Fetal surgery for MMC halves the need for shunt treatment in a select group of MMC pregnancies, constituting a major indication for us to undergo the transition to a fetal surgery center. The fetal benefits of open antenatal surgery for MMC are well established, yet long-term data on especially tethered spinal cord are eagerly awaited.

Prevalence of cystathionine beta synthase gene mutation 852Ins68 as a possible risk for neural tube defects in eastern India. Cystathionine beta synthase gene (CβS) catalyzes the condensation of homocysteine with serine, forming cystathionine by the transsulfuration pathway. Disruption of CβS enzyme activity due to defective folic acid metabolism increases the risk factor for neural tube defects. We evaluated the CβS gene mutation in 25 children with neural tube defects (NTDs), including lumbosacral and thoracic myelomeningocele and open NTDs and mothers of cases, along with 25 healthy children and their mothers, serving as controls. Genomic DNA was isolated to assess the polymorphism of 852Ins68 in the CβS gene using PCR-RFLP analysis and nucleotide sequencing techniques. The 68-bp insertion was observed in one of the 25 NTD cases (lumbosacral myelomeningocele), and in two of the mothers of NTD cases. Statistical analysis was carried out using the Fischer exact probability test, which showed a lack of significance (P > 0.05), but the odds ratio of 2.08 with 95% confidence interval of 0.17-24.6 in NTDs mother was quite high because of the small sample size. However, the study was further extended to find out the involvement of specific nucleotide sequences, which again confirmed the 852Ins68 insertion and replacement of nucleotides (TCCAT to GGGG) in lumbosacral myelomeningocele (due to other category of NTDs), suggesting that it could be an independent risk factor for birth defects, including NTDs.

The control of breast cancer. A World Health Organization perspective. The greatest decrease in breast cancer mortality is likely to derive from applying globally existing therapies at an earlier stage. A high priority of the World Health Organization (WHO) cancer control program is the outreach approach that promotes worldwide access to cancer therapies of proven values. Therefore, the first priority in national health programs for breast cancer is to encourage patients to present for diagnosis and treatment at an earlier stage of the disease. In the development of guidelines for the early detection of breast cancer, the WHO emphasizes the importance of appropriate widespread coverage of high-risk groups as opposed to repetitive screening of low-risk groups, so that early detection will be effective. A WHO/USSR controlled trial of breast self-examination and community-based adjuvant therapy is helping to develop the WHO global recommendations for the control of breast cancer. Depending on the extent of the breast cancer problem, the local resources, and the cultural situation, national health strategies should include all three main elements--public education, early detection, locally available treatment, or a combination of these to a national comprehensive program for the control of breast cancer.

Rolling motion of a bead in a rapid water stream. This paper investigates the two-dimensional rolling motion of a single large particle in a shallow water stream down a steep rough bed from both an experimental and a theoretical point of view. The experiment is prototypal of sediment transport on sloping beds. Two theoretical models are presented. The first model uses the mean kinetic energy balance to deduce the average particle velocity and the bounds of the flow-rate range within which a rolling regime occurs. This range is found to be narrow, which means that the fully rolling regime is a marginal mode of transport between repose and saltation. In the second model, the particle state (resting, rolling, saltating) is considered as a random variable, whose evolution constitutes a jump Markov chain. This makes it possible to deduce the mean particle velocity as a function of the flow conditions without explicit mention of its state. The theoretical results are finally compared to the experimental data. The second model provides correct estimates of the particle velocity and the probability of finding the particle in a given state for various flow conditions (bead material, slope, and roughness).

Exercise myocardial perfusion imaging to evaluate inducible ischaemia in children with Kawasaki disease. Kawasaki disease (KD) is an acute multi-system vasculitis of unknown aetiology, which occurs predominantly in infants and young children. Coronary artery abnormalities may occur in 15-25% of patients who are not treated in the acute phase of the disease with a high dose of intravenous immunoglobulin. Myocardial perfusion imaging is used as a modality to monitor the cardiovascular effects of the disease. The objective of our study was to assess the feasibility and results of exercise myocardial perfusion scintigraphy in children with Kawasaki disease. We performed stress myocardial perfusion imaging in 84 patients suffering from KD. The diagnosis of KD was based on the criteria laid down by the American Heart Association. Myocardial perfusion imaging was performed using either thallium or technetium-99m tetrofosmin. Physical exercise using the Bruce protocol was the most frequent cardiac stressor (74 patients) whereas in few patients (seven patients) dobutamine was used to increase the heart rate. Stress-induced reversible perfusion defects were found only in 12 of the total number of patients. Among these two had coronary artery abnormalities on echocardiography. Four of these patients had achieved adequate heart rate with stress. Two among these patients had a repeat imaging done after 1 year and the perfusion defects showed complete resolution in them. This study thus suggests that reversible perfusion defects are seen in asymptomatic patients with KD and that the presence of perfusion defects may not be associated with echocardiographic demonstration of coronary abnormalities. The treadmill test is a reasonable stress protocol for these patients.

Interpolation and extrapolation in human behavior and neural networks. Unlike most artificial systems, the brain is able to face situations that it has not learned or even encountered before. This ability is not in general echoed by the properties of most neural networks. Here, we show that neural computation based on least-square error learning between populations of intensity-coded neurons can explain interpolation and extrapolation capacities of the nervous system in sensorimotor and cognitive tasks. We present simulations for function learning experiments, auditory-visual behavior, and visuomotor transformations. The results suggest that induction in human behavior, be it sensorimotor or cognitive, could arise from a common neural associative mechanism.

Serum levels of soluble CD23 in patients with asthma or rhinitis monosensitive to Parietaria. Its relation to total serum IgE levels and eosinophil cationic protein during and out of the pollen season. The diagnostic value for allergies of the low affinity IgE receptor and its soluble circulating fragment (sCD23) remains unclear. In particular, little is know about seasonal influences on serum sCD23 levels in subjects with pollen allergy. In the present study, to gain insight into pathophysiological role of sCD23, we have analyzed, in blood from patients allergic to Parietaria sCD23, IgE, and eosinophil cationic protein (ECP) serum levels. IgE were assessed as atopy markers and ECP as an inflammation marker. Patients were studied during and out of pollen season, and results were compared to those obtained in nonallergic subjects. The study population included 42 nonsmoking outpatients, living in Palermo (Sicily, Italy) or in other west Sicilian towns, with a clinical diagnosis of seasonal asthma or rhinitis and monopositive skin test to Parietaria pollen. The group of asthmatic subjects consisted of 25 patients who had one or more of the usual asthma symptoms (wheezing, dyspnea, and cough) only during the pollen season. The group of rhinitis patients consisted of 17 patients, who, during pollen season, had the nasal symptoms (nasal blockage, sneezing, nasal itching, and rhinorrhoea) but no signs of asthma. As a control group, we studied 10 nonatopic subjects from laboratory staff. They had no history of seasonal or perennial rhinitis, asthma, or urticaria and had negative skin tests to a panel of allergens. Soluble CD23, IgE, and ECP were assessed in blood during and out of pollen season. Total serum IgE levels were clearly higher in atopic patients, as classically established. Concerning sCD23 serum levels, a similar pattern of results was obtained. Accordingly, significant correlations were shown between the levels of sCD23 and IgE in all groups of patients. A completely different pattern was observed by analyzing serum ECP levels because ECP levels were significantly increased only in asthmatic patients during pollen season. Accordingly, no significant correlations were observed between the levels of sCD23 and those of ECP. Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent diseases. As demonstrated by the close correlation with total serum IgE values and the lack of correlation with serum ECP values, serum levels of sCD23 appear to be an additional marker for the diagnosis of atopy but not for the follow-up of allergic diseases.

Brain opioids and autism: an updated analysis of possible linkages. Considerable clinical evidence suggests that autistic children lack the normal ability or desire to engage others socially, as indicated by their poor social skills and inappropriate use of language for communicative purposes. Specifically, these children seem to lack normal amounts of social-emotional interest in other people, leading perhaps to a decreased initiative to communicate. This paper summarizes experimental evidence supporting a neurological theory, which posits that autism, at least partially, represents in the brain, such as brain opioids. These substances modulate social-emotional processes, and the possibility that blockade of opioid activity in the brain may be therapeutic for early childhood autism is discussed.

Identification of two forms of fluorine in tissues of rats inhaling hydrogen fluoride. Nonionizable fluorine has been detected in the plasma of several species including the human, however, the exact nature and source of this fluorocompound(s) remain unknown. In the current investigation, the fluoride ion sensitive electrode was employed to determine the fluoride content of ashed (total F) and unashed (ionic F-) tissues of rats exposed to hydrogen fluoride (HF). Total fluorine concentration consistently exceeded ionic fluoride concentration in tissues of HF-exposed rats, suggesting the presence of fluorine in unashed tissue which did not respond to the F- ion sensitive electrode. The concentration of this nonresponding fluorine fraction, termed the delta F fraction, was estimated by subtracting the ionic F- from the total F concentration of each sample. Pulmonary and plasma delta F concentrations increased with time following whole body inhalation exposure to HF. It was possible to separate delta F from ionic F- by calcium phosphate adsorption, indicating that the delta F fraction consists of nonionizable fluorine. Upon Sephadex G-25 gel chromatography, plasma delta F migrated near the bed volume, providing evidence that it is of low molecular weight. Finally, a strong correlation (r = 0.99, p less than 0.01) between plasma delta F concentration and airborne HF concentration was observed, indicating that inorganic fluoride (as HF) is the ultimate source of the low-molecular-weight, nonionizable fluorine species present in tissues of HF-exposed rats.

Aldosterone and cardiovascular disease. The renin-angiotensin-aldosterone system is a co-ordinated hormonal cascade of major importance in the control of fluid and electrolyte homeostasis and blood pressure. During the past decade, the scientific community has realized that this system is also of paramount importance in pathophysiology of cardiovascular and renal target organ damage. In particular, inappropriately elevated aldosterone levels in the face of body sodium expansion have been incriminated in cardiac and vascular inflammation and fibrosis leading to remodeling and disease. Substantial advances on the role and mechanisms of aldosterone-induced tissue damage and novel findings on the genetic control of aldosterone secretion have been reported during the past year, and these are the subjects of this brief review. A novel control mechanism for aldosterone secretion may be circadian clock genes, disruption of which leads to increased aldosterone secretion and hypertension. Animal models for human idiopathic hyperaldosteronism have been reported for the first time. Glucocorticoids have now been found to activate cardiac mineralocorticoid receptors during certain cardiovascular disease states. Crosstalk between mineralocorticoid and angiotensin AT1 receptors contributes to target organ damage. Endogenous cardiotonic steroids may explain at least some of the tissue damage during sodium loading previously attributed to aldosterone. Insights on aldosterone and cardiovascular disease gained during the past year provide new avenues for research and applications for treatment in the future.

Intracellular localization of meso-Tetra(p-sulfophenyl)porphine: a potential tumor localizing agent. The mechanism of meso-tetra (p-sulfophenyl)porphine (TPPS4) localization was examined in Vero and HEp-2 cells in vitro. TPPS4 was found to be relatively nontoxic to both cell types at concentrations up to 200 microgram/ml. However, changes in cellular ultrastructure were observed by electron microscopy, consisting mainly of an increase in membrane-bound vacuoles. The nature of the new structures has not been determined. Both fluorescence microscopy and cellular fractionation indicate that TPPS4 is localized inside the cells studied. Considerable differences in the pattern of localization between the two cell types were found. The TPPS4 in the Vero cells was found to be mainly in the soluble fraction and the red fluorescence was found to be diffuse throughout the cytoplasm. The HEp-2 cells showed TPPS4 fluorescence associated with various cell organelles, predominatly the nucleolus. [14C]-TPPS4 was found in many cellular components but predominantly it was in the soluble and protein fractions. These differences may be significant in the understanding of in vivo localization of this porphyrin in neoplastic tissue.

False-negative results in screening programmes: systematic review of impact and implications. When assessing whether a screening programme is appropriate, there is a particular obligation to ensure that the harms as well as the benefits are considered. Among these harms is the likelihood that false-negative results will occur. In some cases, the consequences of these can be difficult to assess, although false reassurance leading to diagnostic delay and subsequent treatment has been suggested. However, no test is totally accurate (with 100% sensitivity and specificity), and false-negative results are inherent in any screening programme that does not have 100% sensitivity. This review was carried out to assess the medical, psychological, economic and legal consequences of false-negative results that occur in national screening programmes. (1) to determine the consequences of false-negative findings; (2) to investigate how their adverse effects can be minimised; to assess their implications for the NHS, including the impact of false-negatives on public confidence in screening programmes; to identify relevant theoretical perspectives that may be potentially useful when considering the implications of false-negative results. A systematic literature review was carried out. This included a search of 18 electronic databases, various bibliographies and contact with experts to identify relevant literature and perspectives. Outcomes included in the review fell into four categories: medical outcomes (morbidity and mortality); psychological outcomes (distress, false reassurance, loss of confidence in services); economic outcomes (such as costs to the NHS); legal outcomes (such as litigation). Other outcomes, such as the impact of false-negatives on public confidence in screening programmes, were also included. The participants included individuals taking part in screening programmes, healthcare professionals and organisations responsible for screening programmes. Methodological details of the review are provided in the full report. A total of 6660 abstracts were screened, and 420 potentially relevant papers were identified. Most of the studies that were identified presented only anecdotal evidence. (1) Medical outcomes: In all, 13 papers presented quantitative information relevant to the medical consequences of false-negative results; seven of these were primary studies, and the remaining studies were literature reviews or models examining the likely impact of false-negative results. (2) Psychological outcomes: A total of eight published studies presented information on the psychological consequences of negative results in general; only one study, on antenatal screening, provided direct evidence of the psychological consequences of false-negative results, where they were associated with lower parental acceptance of the affected child and with blaming others for this outcome. (3) Economic outcomes: Only two studies presented information on the economic consequences. The strength of evidence from most of the primary studies was low. There is some evidence that false-negative results may have a large legal impact. For example, in cervical screening they have led to legal action and its associated costs, including payment of compensation; this is based on reports of events in both the UK and US health systems. There also seems to be a consensus in the literature that false-negatives may have a negative impact on public confidence in screening; evidence is again limited however. False-negatives are evident in all screening programmes, even when the quality of the service provided is high. They may have the potential to delay the detection of breast and cervical cancer, but there is little evidence to help assess their psychological consequences in these or other screening programmes. False-negatives are likely to lead to legal action being taken by those individuals affected, and potentially may reduce public confidence in screening. (ABSTRACT TRUNCATED)

The angiocardiographic diagnosis of a persistent truncus arteriosus in a foal. Persistent truncus arteriosus is a relatively rare cardiac anomaly which is associated with a single large artery arising from the ventricles. An interventricular septal defect is invariably present. The vessel gives origin to the pulmonary trunk, aorta and coronary arteries. A description of the angiocardiographic diagnosis of this condition is given as well as a general review of the relative developmental anatomy.

Laterality in hand preferences and reaching accuracy of cotton-top tamarins (Saguinus oedipus). Manual laterality of cotton-top tamarins (Saguinus oedipus) was observed for five different types of reaching. The tamarins displayed species-level right-handedness for spontaneous grasping for food but not for one-arm vertical suspension or any of 3 other types of elicited reaching. The results showed that difficult or novel tasks are neither necessary nor sufficient for the emergence of species-level handedness. Accuracy in retrieving food from a rotating platform was greatest (a) for highly lateralized tamarins, (b) when the preferred hands were used for reaching, (c) for young tamarins, and (d) when the tamarins stood on a narrow, unstable platform instead of a wide, stable one. The results suggest that evolution of species-level handedness is dependent on prior natural selection for increased manual performance that accompanies strongly lateralized hand preferences.

Relative contribution of Peyer's patches to intestinal DNA content and tritiated thymidine content of the mouse small intestine. The quantification of mucosal DNA as a measure of epithelial cellularity has been criticized because it would include the non-epithelial cell populations present in the mucosa. The weight, DNA content and tritiated thymidine uptake of Peyer's patches and the remaining mucosa were measured and compared. Although the Peyer's patches only contribute 2.5% to the weight of the small intestine, they contained 12% of the DNA and 7% of the tritiated thymidine which would be found in a mucosal scrape.

Entrainment of the mouse circadian clock: Effects of stress, exercise, and nutrition. The circadian clock system in mammals plays a fundamental role in maintaining homeostasis. Entrainment is an important characteristic of the internal clock, by which appropriate timing is maintained according to external daily stimuli, such as light, stress, exercise, and/or food. Disorganized entrainment or a misaligned clock time, such as jet lag, increases health disturbances. The central clock in the suprachiasmatic nuclei, located in the hypothalamus, receives information about arousal stimuli, such as physical stress or exercise, and changes the clock time by modifying neural activity or the expression of circadian clock genes. Although feeding stimuli cannot entrain the central clock in a normal light-dark cycle, the central clock can partially detect the metabolic status. Local clocks in the peripheral tissues, including liver and kidney, have a strong direct response to the external stimuli of stress, exercise, and/or food that is independent of the central clock. The mechanism underlying entrainment by stress/exercise is mediated by glucocorticoids, sympathetic nerves, oxidative stress, hypoxia, pH, cytokines, and temperature. Food/nutrition-induced entrainment is mediated by fasting-induced hormonal or metabolic changes and re-feeding-induced insulin or oxyntomodulin secretion. Chrono-nutrition is a clinical application based on chronobiology research. Future studies are required to elucidate the effects of eating and nutrient composition on the human circadian clock. Here, we focus on the central and peripheral clocks mostly in rodents' studies and review the findings of recent investigations of the effects of stress, exercise, and food on the entrainment system.

Eye movement responses to active, high-frequency pitch and yaw head rotations in subjects with unilateral vestibular loss or posterior semicircular canal occlusion. This study assessed the eye movement responses to active head rotation in six subjects with complete unilateral vestibular loss (UVL), five subjects with posterior canal plugging (PCP) and age- and sex-matched normal subjects. Subjects performed head rotations in the pitch and yaw planes at frequencies ranging from 2 to 6 Hz, while looking at an earth-fixed target. Vertical eye movement gains obtained in UVL, PCP and normal subjects were not significantly different. Vertical phases decreased with increasing head movement frequencies in both UVL and PCP subjects. Although this decrease produced significantly different vertical phases between UVL and normal subjects for head movements above 3.9 Hz, vertical phases in some normal subjects were similar to those obtained in UVL subjects. We conclude that active head oscillations in the pitch plane are not clinically useful for the detection of vertical canal impairment limited to one ear. As expected, UVL subjects showed reduced horizontal gains, and eye velocity asymmetries during active head rotation in the yaw plane. Results in some PCP subjects suggested possible minor impairments of horizontal vestibulo-ocular reflexes.

Adsorption of plasma proteins on to poly(ethylene oxide)/poly(propylene oxide) triblock copolymer films: a focus on fibrinogen. Triblock copolymers of the form PEO(alpha)PPO(beta)PEO(alpha) [where PEO is poly(ethylene oxide) and PPO is poly(propylene oxide)] have many biomedical applications, many of which depend on the surface properties of the copolymers and the influence that those properties have on the adsorption of proteins. As a tool to help us better understand, predict and exploit the influence of these triblock copolymers on protein adsorption, we developed a model system in which well-defined monolayers of the copolymers are supported by solid, hydrophobic, microscopic beads. At the bead/water interface, the copolymers all form stable films in which the nominal molecular areas correspond to those of the molecules when they are packed rather tightly at the air/water interface. Beads coated with condensed films of copolymers that contain short PEO segments and elicit appreciable inflammation absorb appreciable quantities of plasma proteins, including fibrinogen, from aqueous solution. Beads coated with fibrinogen aggregate when they are stirred in the presence of thrombin, a consequence of interbead fibrin formation. Beads coated with condensed films of copolymers that contain long PEO segments and elicit little inflammation absorb little plasma protein, and they do not aggregate in the presence of thrombin. Our data and observations are consistent with the prevailing notion that the utility of triblock copolymers as agents for modifying the surface properties of blood-contacting surfaces derives from the influence of the copolymers on the adsorption of plasma proteins. In this regard, the ability of the copolymers to influence fibrinogen-mediated adhesive events may be particularly important. As to the mechanism of protein resistance, our data support the proposal that sibling PEO segments of copolymers in condensed films fold back across their parental PPO cores, limiting access of proteins to the hydrophobic cores themselves.

The effect of excisional biopsy on the accuracy of sentinel lymph node mapping in early stage breast cancer: comparison with core needle biopsy. Despite the successful application of sentinel node mapping in breast cancer patients, its use in patients with a history of previous excisional biopsy of the breast tumors is a matter of controversy. In the present study we evaluated the accuracy of sentinel node biopsy in this group of patients and compared the results with those in whom the diagnosis of breast cancer was established by core needle biopsy. Eighty patients with early stage breast carcinoma were included into our study. Forty patients had a history of previous excisional biopsy and the remainder 40 had undergone core needle biopsy. Intradermal injections of 99mTc-antimony sulfide colloid as well as patent blue were both used for sentinel node mapping. Sentinel nodes were harvested during surgery with the aid of surgical gamma probe. All patients underwent standard axillary lymph node dissection subsequently. Detection rate was 97.5 per cent for both groups of the study. Number of detected sentinel node during surgery was not significantly different between groups. False negative rate was 0 per cent for both groups of the study. In conclusion sentinel node biopsy is reliable in patients with previous history of excisional biopsy of the breast tumors and has a low false negative rate.

Supramolecular assemblies obtained by mixing different cyclodextrins and AOT or BHDC reverse micelles. In this contribution we show the effect of the surfactant polar head and the external solvent on the incorporation of different cyclodextrins (CDs) {α-CD, β-CD, γ-CD, decenylsuccinyl-β-CD (Mod-β-CD), and hydroxypropyl-β-CD (hp-β-CD)} in different reverse micelles (RMs) {benzene/sodium 1,4-bis(2-ethylhexyl) sulfosuccinate(AOT)/water, and benzene/benzyl-n-hexadecyldimethylammonium chloride (BHDC)/water} and compare them with previous results obtained in n-heptane/AOT/water RMs. To investigate the different systems, we have used UV-vis spectrophotometry, induced circular dichroism spectroscopy (ICD), and the achiral molecular probe methyl orange (MO). The results show dramatic differences changing the external solvent and the surfactant, which are explained by considering the differences in the RMs interface composition, the water-surfactant interaction, and the CDs' location in the different media investigated. None of the CDs were incorporated into the benzene/AOT/water RMs at any [H2O]/[surfactant] ratio studied (W0) whereas it was previously shown that Mod-β-CD and hp-β-CD could be included in n-heptane/AOT/water RMs. However, all of the CDs are incorporated in benzene/BHDC/water RMs at W0 > 10 and hp-β-CD is dissolved even at W0 = 0. Different from what was found in n-heptane/AOT RMs, in BHDC RMs MO showed ICD signals with two different CDs: Mod-β-CD and hp-β-CD. The results are explained by considering the known difference in the interfacial water structure for AOT and BHDC RMs and the electron-rich region on the secondary hydroxyl (wider side of the CDs), which helps to solubilize all CDs in BHDC. This study shows that chiral cyclodextrin could be available for a guest in an organic medium such as the RMs. Therefore we have created a potentially powerful nanoreactor with two different confined regions in the same aggregate: the polar core of the RMs and the chiral hydrophobic cavity of cyclodextrin.

Testis and gonopodium development in Anableps Dowi (Pisces: Anablepidae) correlated with pituitary gonadotropic zone area. Testicular development in the viviparous fish, Anableps dowi, is described from embryonic stages through sexual maturation and is correlated with development of the gonadotropic zone of the pituitary. Only isolated spermatogonia or cysts of early spermatogonia are found in embryos 1.8 to 4.4 cm in length and postnatal specimens 5.4 to 8.8 cm in length. Cysts with more advanced spermatogonia are seen in specimens from 7.9 to 10.8 cm in length. Spermatogenetic meioses are first observed in a 10.2 cm male. Specimens greater than 12.0 cm have mature spermatozoa (partial spermatozeugmata) within the main testicular ducts, indicating gonadal maturation. The morphological transformation of the anal fin into the intromittent gonopodium is also described, using both whole and cleared specimens. Even in the smallest postnatal male available (5.4 cm), the anal fin can be distinguished from that of an equivalent sized female. Anal fin changes proceed until the mature gonopodium is developed, when body lengths greater than 16 cm are reached. Testicular maturation, defined as the presence of partial spermatozeugmata in the main testicular ducts, precedes the completion of gonopodial development. Measurements of ventral gonadotropic zone area in pituitary mid-sagittal sections show a continuous increase from neonatal through sexually mature specimens. The results point to a role for testicular androgens in early testis development.

Psychophysiological characteristics of narcissism during active and passive coping. This study provides the first psychophysiological analysis of narcissism by measuring autonomic responses during active and passive anticipatory coping in 40 undergraduate men who scored high or low on the Narcissistic Personality Inventory (NPI). Compared to the low NPI group, the high NPI group showed greater preejection period (PEP) shortening, cardiac deceleration, and skin conductance response (SCR) habituation during anticipation of an aversive stimulus (p < .02). As expected, SCR and PEP reactivity were greater during active than passive coping. In the case of PEP, this effect emerged only in the low NPI group; the high NPI group showed the greatest PEP reactivity during the first task, regardless of coping demands. These data support hypothesized relationships among narcissism, psychopathy, and psychological predictors of cardiovascular disease, and suggest that a psychobiological dimension may underlie important features of narcissism.

Two fatal cases of hepatitis B virus carriers after corticosteroid therapy for bronchial asthma. We report two hepatitis B virus (HBV) carriers who had liver failure after withdrawal of corticosteroids (steroids) administered for treatment of serious asthmatic attacks. Liver functions deteriorated 1 to 2 wk after withdrawal of the steroid therapy and liver failure occurred. Steroid readministration and intensive therapy for liver failure did not prevent death. An excessive immune response provoked by steroid withdrawal and decreased reserve capacity due to underlying chronic liver disease were thought to be factors in the liver failure. Caution must be exercised in the administration of steroids to patients with underlying chronic HBV infection to prevent exacerbation of hepatitis. Prompt readministration of steroids is indicated if evidence of liver failure develops.

Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP. Glioblastomas (GBL) are the most common and aggressive brain tumors. They are distinguished by high resistance to radiation and chemotherapy. To find novel approaches for GBL classification, we obtained 16 primary GBL cell cultures and tested them with real-time PCR for mRNA expression of several genes (YB-1, MGMT, MELK, MVP, MDR1, BCRP) involved in controlling cell proliferation and drug resistance. The primary GBL cultures differed in terms of proliferation rate, wherein a group of GBL cell cultures with low proliferation rate demonstrated higher resistance to temozolomide. We found that GBL primary cell cultures characterized by high proliferation rate and lower resistance to temozolomide expressed higher mRNA level of the YB-1 and MDR1 genes, whereas upregulated expression of MVP/LRP mRNA was a marker in the group of GBL with low proliferation rate and high resistance. A moderate correlation between expression of YB-1 and MELK as well as YB-1 and MDR1 was found. In the case of YB-1 and MGMT expression, no correlation was found. A significant negative correlation was revealed between mRNA expression of MVP/LRP and MELK, MDR1, and BCRP. No correlation in expression of YB-1 and MVP/LRP genes was observed. It seems that mRNA expression of YB-1 and MVP/LRP may serve as a marker for GBL cell cultures belonging to distinct groups, each of which is characterized by a unique pattern of gene activity.

Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis. In the present study we analysed the neuroprotective effect of the L-type voltage-dependent calcium channel antagonist verapamil on cholineacetyltransferase (ChAT)-immunoreactive neurons in the cerebral cortex of rats with bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM). Treatment with verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg/12 h i.p.) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM-lesions. The bilateral NBM-lesions produced significant loss of ChAT-immunoreactive neurons in frontal, parietal and temporal cortex. Although the number of ChAT-positive neurons was significantly higher in NBM-lesioned animals treated with verapamil at a dose of 2.5, 5.0 and 10.0 mg/kg than in saline treated ones, the most significant effect was obtained at a dose of 5 mg/kg. This is, to our knowledge, the first report showing an inverted U-shape mode of neuroprotective action of the calcium antagonist verapamil, at morphological level in this particular model of brain damage. The demonstrated beneficial effect of verapamil treatment suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a possible treatment to prevent neurodegenerative processes in the rat cerebral cortex.

Receptive field mechanisms of ganglion cells in the cat retina. On the basis of anatomical and physiological results of the vertebrate retina, a method is proposed for analysing the respective fields of ganglion cells in the cat retina. In the model, we assume the following: (a) Ganglion cells receive their input from bipolar and/or amacrine cells. (b) The nonlinearity of ganglion cell responses is due to the activities of transient type amacrine cells. The method has been proved to be effective. According to the results of this investigation, the receptive field properties of X type and Y type ganglion cells are heterogeneous. Thus, it may be considered that their receptive fields consist of center and surround mechanisms. The receptive field properties of X-cells are almost linear and the X-cells seem to receive most of their input from bipolar cells. On the other hand, the ones of Y-cells are highly nonlinear. Consequently, it is conceivable that the Y-cells receive their input mainly from transient type amacrine cells.

Cell-free synthesis, membrane integration, and glycosylation of pro-sucrase-isomaltase. Cell-free translation of total RNA from rabbit intestinal mucosa in a rabbit reticulocyte lysate, after immunoprecipitation with antibodies directed against sucrase-isomaltase, yielded a polypeptide of 200 kDa, which was identified as pro-sucrase-isomaltase. Addition of dog pancreatic microsomal vesicles to the translation system resulted in the appearance of an additional 220-kDa polypeptide. The 220-kDa polypeptide was associated with the membranes in a way that made it inaccessible to proteolysis; this protection was abolished by lytic detergent concentrations, indicating that the polypeptide was segregated into the microsomal vesicle. The 220-kDa polypeptide was glycosylated as evidenced by it being bound to concanavalin A-Sepharose and eluted with alpha-methyl-D-mannopyranoside. The increase in apparent molecular mass (approximately 20 kDa) of the primary translation product upon translocation was due to the addition of carbohydrate; treatment of the 220-kDa polypeptide with endo-beta-N-acetylglucosaminidase H increased its electrophoretic mobility to that of the 200-kDa polypeptide which was obtained in the absence of membranes. Partial N-terminal amino acid sequence of a translation product labeled with [3H]Leu in the absence of membranes revealed that Leu was incorporated into identical positions as in the final (pro)-sucrase-isomaltase, thus indicating the lack of a transient signal peptide.

ATP-evoked membrane current in guinea pig adrenal chromaffin cells. Adenosine 5'-triphosphate (ATP) evoked an inward current in whole-cell voltage-clamped adrenal chromaffin cells of the guinea pig. The reversal potential (Erev) of ATP-evoked current was about 0 mV in normal external solution and was shifted towards negative potentials by substituting Tris+ or sucrose, but not Ca2+, for the extracellular Na+. This current was mediated by the activation of non-selective cation channels and had some different properties from nicotinic current. It is suggested that these channels may function as a part of the ATP-induced Ca2+ influx pathway in guinea pig chromaffin cells.

Father's involvement and its effect on early breastfeeding practices in Viet Nam. Fathers have an important but often neglected role in the promotion of healthy breastfeeding practices in developing countries. A community-based education intervention was designed to mobilize fathers' support for early breastfeeding. This study aimed to evaluate an education intervention targeting fathers to increase the proportion of early breastfeeding initiation and to reduce prelacteal feeding. Quasi-experimental study design was used to compare intervention and control areas located in two non-adjacent rural districts that shared similar demographic and health service characteristics in northern Viet Nam. Fathers and expectant fathers with pregnant wives from 7 to 30 weeks gestational age were recruited. Fathers in the intervention area received breastfeeding education materials, counselling services at a commune health centre and household visits. They were also invited to participate in a breastfeeding promotion social event. After intervention, early breastfeeding initiation rate was 81.2% in the intervention area and 39.6% in the control area (P < 0.001). Babies in the intervention area were more likely to be breastfed within the first hour after birth [odds ratio (OR) 7.64, 95% confidence interval (CI) 4.81-12.12] and not to receive any prelacteal feeding (OR 4.43, 95% CI 2.88-6.82) compared with those in the control area. Fathers may positively influence the breastfeeding practices of mothers, and as a resource for early childcare, they can be mobilized in programmes aimed at improving the early initiation of breastfeeding.

Assessment of microsatellite instability in bladder and thyroid malignancies. Microsatellite instability (MSI) is an indicator of a defective DNA mismatch repair system (MMR) that results from somatic mutations. The present work has been planned to investigate MSI and its clinical significance in human urinary bladder and thyroid cancers in Indian patients. Tumor tissues of histologically confirmed cases of urinary bladder and thyroid cancers, respectively, were obtained. Clinical data on tumor stage and histopathological grades were recorded. Corresponding matched peripheral blood was taken as a control. Genomic DNA was isolated from the tumor tissues and blood using a standard phenol-chloroform extraction method. Polymerase chain reaction was done to amplify mononucleotide microsatellite markers, BAT-26, BAT-40, TGFbetaRII, IGFIIR, hMSH3, and Bax by using specific primer sequences. For analysis of allelic patterns, the PCR products were run on 8% denaturing Polyacrylamide gel and sizing was done using a pUC18 sequencing ladder. The instability with BAT-26 and BAT-40 was found to be 20% and 45% in urinary bladder and 33% and 19% in thyroid cancers, respectively. However, no instability was observed with the other four-mononucleotide markers in either of the cancers studied. Eighty-three percent of the unstable urinary bladder cancers were found to have a high grade in a superficial group, whereas only 27% MSI+ve were muscle invasive cancers. Forty percent of unstable thyroid lesions were found to be at high risk of developing metastasis. Association of BAT-26 and BAT-40 instabilities with high grade tumors as well as risk tumors may help in choosing a more definite therapy at the outset.

Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Purpose: Evaluation of the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS). Materials and methods: Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on Day 1) or repeat dose (5.0 mg/kg on Days 1 and 8), pegfilgrastim alone as a repeat dose (0.3 µg/kg on Day 1 and 8), or a combination of both agents (romiplostim 5.0 mg/kg on Day 1; pegfilgrastim 0.3 µg/kg on Days 1 and 8). Clinical outcome, hematological parameters and PK were assessed throughout the 45 d study period post-irradiation. Results: Administration of romiplostim, pegfilgrastim or the combination of both resulted in significant improvements in hematological parameters, notably prevention of severe thrombocytopenia, compared with irradiated, vehicle control-treated NHPs. The largest hematologic benefit was observed when romiplostim and pegfilgrastim were administered as a combination therapy with much greater effects on both platelet and neutrophil recovery following irradiation compared to single agents alone. Conclusions: These results indicate that romiplostim alone or in combination with pegfilgrastim is effective at improving hematological parameters in an NHP model of ARS. This study supports further study of romiplostim as a medical countermeasure to improve primary hemostasis and survival in ARS.

Allotypes associated with B apolipoproteins in rabbits. Western blot analysis of the alloantisera (i.e., anti-Lpq1, anti-Lpq2, anti-Lpq3, and anti-Lpq4) which defined the three lpq genes of rabbit linkage group VIII showed that they reacted strongly with an apolipoprotein of molecular weight 320,000. They also cross-reacted with an apolipoprotein of molecular weight 220,000. The two apolipoproteins that reacted with the alloantisera were found by SDS-polyacrylamide gel electrophoresis to be present in very low density (VLDL), intermediate density (IDL), and low density (LDL) lipoprotein fractions and by Western blot analysis to react with an anti-apolipoprotein B antiserum. These results support the conclusion that the alloantisera react with allotypes associated with the B apolipoproteins. The distribution of the four allotypes among different lipoprotein fractions, however, differed. The quantitative competitive Enzyme Linked Immunosorbant Assay (ELISA) showed that the Lpq1, Lpq2, and Lpq4 allotypes were found in the highest concentration in VLDL, IDL, and LDL, and in significantly lower concentrations in plasma chylomicrons. The concentrations of these allotypes in high density lipoproteins (HDL) as measured in the ELISA were about 1% of the concentrations found in LDL. The Lpq3 allotype, on the other hand, was present in the highest concentrations only in IDL and LDL and in significantly lower concentrations in VLDL and plasma chylomicrons. Surprisingly, the concentration of the Lpq3 allotype in HDL was 20% of the level found in LDL.

Quantifying male-biased dispersal among social groups in the collared peccary (Pecari tajacu) using analyses based on mtDNA variation. Recent advances in the statistical analysis of microsatellite data permit calculation of sex-specific dispersal rates through sex- and age-specific comparisons of genetic variation. This approach, developed for the analysis of data derived from co-dominant autosomal markers, should be applicable to a sex-specific marker such as mitochondrial DNA. To test this premise, we amplified a 449 bp control region DNA sequence from the mitochondrial genome of the collared peccary (Pecari tajacu), and estimated intra-class correlations among herds sampled from three Texas populations. Analyses on data partitioned by breeding group showed a clear signal of male-biased dispersal; sex-specific fixation indices associated with genetic variation among social groups within populations yielded values for females (F(GP)=0.91), which were significantly larger than values for males (F(GP)=0.24; P=0.0015). The same general pattern emerged when the analyses were conducted on age classes (albeit nonsignificantly), as well as categories of individuals that were predicted a posteriori to be dispersers (adult males) and philopatric (adult females and all immatures). By extending a previously published methodology based on biparentally inherited markers to matrilineally inherited haploid data, we calculated sex-specific rates of contemporary dispersal among social groups within populations (m(male symbol)=0.37). These results support the idea that mitochondrial DNA haplotype frequency data can be used to estimate sex-specific instantaneous dispersal rates in a social species.

Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. We review the information obtained by 13C NMR methods on the metabolic compartmentation of the adult mammalian brain with emphasis on its quantitative aspects. Classical radiotracer evidence and more recent 13C NMR results support the presence in the brain of at least two glutamate pools, small and large, associated with two kinetically different tricarboxylic acid cycles localized in glia and neurons, respectively. Neuronal and glial cycles interact closely, utilizing common substrates like glucose and oxygen and exchanging a variety of metabolites including glutamate, glutamine and GABA. A model for the cerebral metabolism of (1,2-13C2) acetate has made it possible to calculate fluxes through both cycles and evaluate the exchanges of glutamate, glutamine and GABA under different physiopathological conditions. Calculated flux values through the neuronal and glial tricarboxylic acid cycles are 1.0 and 0.4 mumol/min g, respectively. In the adult normoxic brain, the small and large glutamate pools account for approximately 10% and 90% of cerebral glutamate with estimated turnover times of 1.25 and 5.8/min, respectively. Net transfers of neuronal glutamate and GABA to the glial compartment are calculated to be 0.1 and 0.04 mumol/min g while transfer of glial glutamine to the neuronal compartment is estimated as 0.1 mumol/min g. Pyruvate recycling in the adult brain occurs mainly in the synaptic terminals with a calculated flux of 0.3 mumol/min g. These flux values are altered severely in pathological states such as hypothyroidism or ischemia.

Optimized molecular reconstruction procedure combining hybrid reverse Monte Carlo and molecular dynamics. We report an efficient atom-scale reconstruction method that consists of combining the Hybrid Reverse Monte Carlo algorithm (HRMC) with Molecular Dynamics (MD) in the framework of a simulated annealing technique. In the spirit of the experimentally constrained molecular relaxation technique [Biswas et al., Phys. Rev. B 69, 195207 (2004)], this modified procedure offers a refined strategy in the field of reconstruction techniques, with special interest for heterogeneous and disordered solids such as amorphous porous materials. While the HRMC method generates physical structures, thanks to the use of energy penalties, the combination with MD makes the method at least one order of magnitude faster than HRMC simulations to obtain structures of similar quality. Furthermore, in order to ensure the transferability of this technique, we provide rational arguments to select the various input parameters such as the relative weight ω of the energy penalty with respect to the structure optimization. By applying the method to disordered porous carbons, we show that adsorption properties provide data to test the global texture of the reconstructed sample but are only weakly sensitive to the presence of defects. In contrast, the vibrational properties such as the phonon density of states are found to be very sensitive to the local structure of the sample.

Nestin serves as a prosurvival determinant that is linked to the cytoprotective effect of epidermal growth factor in rat vascular smooth muscle cells. Nestin is an intermediate filament protein mainly expressed in muscle and neural progenitors. Recently, we reported that nestin is expressed in rat vascular smooth muscle cells (VSMCs), disappears after serum-deprivation and then is re-expressed again following EGF stimulation. As the function of nestin in VSMCs remains unknown, its anti-apoptotic function was investigated in this study. We first showed that cell viability of nestin-depleted cells following H(2)O(2) treatments decreased by nestin RNAi. Further DNA laddering analysis and flow cytometry results demonstrated that this loss of cell viability was mediated through apoptosis. In addition, caspase-9, caspase-3 and PARP were activated in nestin-depleted VSMCs following H(2)O(2) treatments, indicating that nestin has an upstream inhibitory effect on caspase activation. It is well known that EGF serves as a survival factor in rat VSMCs. Here, we show that the cytoprotective effect of EGF was prevented by nestin RNAi. In addition, the inhibition of Cdk5 prevented Bcl-2 phosphorylation and enhanced H(2)O(2)-induced caspase-3 activation as well as subsequent DNA fragmentation. Taken together, these results provide evidence for another cytoprotective role of EGF in that it is mediated through its stimulation of nestin expression which leads to the prevention of caspase activation by Cdk-5-induced Bcl-2 phosphorylation in rat VSMCs.

Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Enhances the Expression of Angiogenic Factors in a Mouse Acute Hindlimb Ischemic Model. Cell migration and molecular mechanisms during healing of damaged vascular or muscle tissues are emerging fields of interest worldwide. The study herein focuses on evaluating the role of allogenic adipose-derived mesenchymal stem cells (ADMSCs) in restoring damaged tissues. Using a hindlimb ischemic mouse model, ADMSC-mediated induction of cell migration and gene expression related to myocyte regeneration and angiogenesis were evaluated. ADMSCs were labeled with GFP (ADMSC-GFP). The proximal end of the femoral blood vessel of mice (over 6 months of age) are ligated at two positions then cut between the two ties. Hindlimb ischemic mice were randomly divided into two groups: Group I (n = 30) which was injected with PBS (100 μL) and Group II (n = 30) which was transplanted with ADMSC-GFP (106 cells/100 μL PBS) at the rectus femoris muscle. The migration of ADMSC-GFP in hindlimb was analyzed by UV-Vis system. The expression of genes related to angiogenesis and muscle tissue repair was quantified by real-time RT-PCR. The results showed that ADMSCs existed in the grafted hindlimb for 7 days. Grafted cells migrated to other damaged areas such as thigh and heel. In both groups the ischemic hindlimb showed an increased expression of several angiogenic genes, including Flt-1, Flk-1, and Ang-2. In particular, the expression of Ang-2 and myogenic-related gene MyoD was significantly increased in the ADMSC-treated group compared to the PBS-treated (control) group; the expression increased at day 28 compared to day 3. The other factors, such as VE-Cadherin, HGF, CD31, Myf5, and TGF-β, were also more highly expressed in the ADMSC-treated group than in the control group. Thus, grafted ADMSCs were able to migrate to other areas in the injured hindlimb, persist for approximately 7 days, and have a significantly positive impact on stimulating expression of myogenic- and angiogenesis-related genes.

Hand-assisted hybrid laparoscopic-robotic total proctocolectomy with ileal pouch--anal anastomosis. Few studies have reported minimally invasive total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We herein report a novel hand-assisted hybrid laparoscopic-robotic technique for patients with FAP and UC. Between February 2010 and March 2014, six patients underwent hand-assisted hybrid laparoscopic-robotic total proctocolectomy with IPAA. The abdominal colectomy was performed laparoscopically with hand assistance through a transverse suprapubic incision, also used to fashion the ileal pouch. The proctectomy was carried out with the da Vinci Surgical System. The IPAA was hand-sewn through a trans-anal approach. The procedure was complemented by a temporary diverting loop ileostomy. The mean hand-assisted laparoscopic surgery (HALS) time was 154.6 (±12.8) min whereas the mean robotic time was 93.6 (±8.1) min. In all cases, a nerve-sparing proctectomy was performed, and no conversion to traditional laparotomy was required. The mean postoperative hospital stay was 13.2 (±7.4) days. No anastomotic leakage was observed. To date, no autonomic neurological disorders have been observed with a mean of 5.8 (±1.3) bowel movements per day. The hand-assisted hybrid laparoscopic-robotic approach to total proctocolectomy with IPAA has not been previously described. Our report shows the feasibility of this hybrid approach, which surpasses most of the limitations of pure laparoscopic and robotic techniques. Further experience is necessary to refine the technique and fully assess its potential advantages.

Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by oxytocin in ovariectomized rats. The effects of oxytocin on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in ovariectomized rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of oxytocin (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK1 receptor antagonists, devazepide and lorglumide, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK2 receptor antagonist, did not alter the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that oxytocin inhibits gastric emptying and gastrointestinal transit in ovariectomized rats via a mechanism involving the stimulation of CCK release and CCK1 receptor activation.

A DNA biosensor based on a morpholino oligomer coated indium-tin oxide electrode and a cationic redox polymer. A simple and ultrasensitive electrochemical biosensor employing a morpholino oligomer as capture probe and a cationic redox polymer as signal generator for direct detection of DNA is presented in this report. It is based on the immobilization of the morpholino oligomer on an indium-tin oxide (ITO) electrode and amperometric detection of target DNA by forming a DNA/cationic redox polymer bilayer on the ITO electrode. After hybridizing the morpholino capture probe (MCP) to the target DNA, the cationic redox polymer was introduced to the ITO electrode via electrostatic interaction with the hybridized DNA. The deposited redox polymer exhibited excellent electrocatalytic activity towards the oxidation of ascorbic acid (AA), allowing for direct voltammetric and amperometric detection of DNA. Under optimized experimental conditions, a detection limit of 1.0 pM and linear current-concentration relationship up to 500 pM were obtained in amperometry. The resulting biosensors offered much better mismatch discrimination against mismatch sequences than their DNA counterparts.

Intestinal perforation. An infrequent complication of ventriculo-peritoneal shunts. Bowel perforation by ventriculo-peritoneal shunts occurred in two children with no abdominal symptoms. The diagnosis in each instance was confirmed by opacification of the colon in one child and the small bowel in the other via contrast medium injection of the distal shunt tubing. "Shuntograms" are recommended for all patients with no readily evident cause of dysfunctioning cerebrospinal fluid-peritoneal shunts.

Preoperative evaluation of patients with bladder outlet obstruction with particular regard to excretory urography. During the last 15 years excretory urography has been a routine preoperative diagnostic procedure for patients with bladder outlet obstruction in our department and, perhaps, for many more years in other urological centers. There are 2 reasons that this investigation should be done: 1) to detect abnormalities of the upper urinary tract that can be important indicators to operate or for the postoperative course and 2) to detect abnormalities in the bladder that should be corrected simultaneously with the prostatectomy or that can interfere with the procedure.

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1-q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. Five novel missense mutations were identified: four in the alpha-helical-rod domain of the lamin A/C gene, and one in the lamin C tail domain. Each mutation caused heritable, progressive conduction-system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Serum creatine kinase levels were normal in family members with mutations of the lamin rod but mildly elevated in some family members with a defect in the tail domain of lamin C. Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.

Somatomedin-C and platelet-derived growth factor stimulate human fibroblast replication. Previous studies have demonstrated that serum contains mitogens, such as platelet-derived growth factor (PDGF), which may alter fibroblast responsiveness to growth factors contained in plasma. Somatomedin-C (SM-C) has been identified as one of the plasma growth factors required for mouse Balb/c 3T3 fibroblasts to initiate DNA synthesis. The present experiments were undertaken to explore the interaction between PDGF, human growth hormone (hGH), SM-C, and other growth-promoting agents in stimulating the growth of human fibroblasts. Proliferation of human dermal fibroblasts plated at low density (3,000 cells/cm2) was found to be equally stimulated by continuous exposure to either normal or somatomedin-C-deficient serum. In contrast, when confluent monolayers were sequentially exposed to PDGF, followed either by normal platelet poor plasma (PPP) or hypopituitary PPP, the cells exposed to normal PPP entered the "S" phase of the cell cycle 50% faster. This difference could be abolished by a 6-hour incubation with growth hormone (10 ng/ml) or somatomedin-C (5 ng/ml) preceding the addition of plasma. When medium containing either hGH or Sm-C was changed frequently so as to remove factors secreted by fibroblasts only those cells exposed to exogeneous somatomedin-C entered DNA synthesis. This finding is in agreement with previous findings that human fibroblasts are capable of making Sm-C in response to hGH. These findings support the hypothesis that somatomedin is required for fibroblast replication in vitro, and that growth hormone appears to stimulate replication indirectly through somatomedin production.

MOTOR NERVE CONDUCTION VELOCITIES OF THE MEDIAN AND SCIATIC-TIBIAL NERVES IN EIGHT NORMAL LARGE FLYING FOXES ( PTEROPUS VAMPYRUS). Electrodiagnostic testing is an integral part of the evaluation of the motor unit in many neurologic conditions. Literature about the peripheral nervous system of flying foxes ( Pteropus spp) is sparse, and reference range values for motor nerve conduction velocities in vivo have not been established in Chiropterans. The goals of this study were to determine reference range conduction velocities in flying fox for the thoracic and pelvic limb nerve. Eight Pteropus vampyrus, large flying foxes, of varying ages and gender underwent nerve conduction studies of the median nerve and sciatic-tibial nerve. Mean (SD) conduction velocity values were 49.8 (12.7) m/sec for the median nerve and 42.1 (10.2) m/sec for the sciatic-tibial nerve. Median nerve conduction velocities were not significantly faster than sciatic-tibial nerve conduction velocities, although a trend was seen. Differences by sex or age class were not statistically significant. It was also noted that flying foxes rapidly lose body heat under general anesthesia.

[Carcinoma in situ of the bladder. Apropos of 10 cases]. 10 cases of primary carcinoma in situ are described and the symptomatology of the disease is analysed. The role of cytodiagnosis is emphasised. The evolution is variable. In 2 cases the bladder became totally retracted and total cystectomy had to be performed in spite of the fact that the lesion remained intra-urothelial. Invasive cancer developped only in 2 cases: 7 and 6 years after diagnosis. Conservative treatment by Tur seems logical whilst the carcinoma remains strictly "in situ".

Differences in natural history of low- and high-gradient aortic stenosis from nonsevere to severe stage of the disease. The aim of the present study was to assess and compare the disease progression of aortic stenosis (AS) subtypes from nonsevere to severe disease on the basis of measures of gradient and flow. Seventy-seven patients with AS (mean aortic valve area, 1.3 ± 0.3 cm(2) at baseline) underwent echocardiographic examination, including two-dimensional speckle-tracking strain measurements. Patients were retrospectively grouped according to mean transvalvular pressure gradient (40 mm Hg) into low-gradient (LG/AS) and high-gradient (HG/AS) groups. The LG/AS group was further subdivided into low-flow (LF/LG; i.e., stroke volume index < 35 mL/m(2)) and normal-flow (NF/LG) groups. For subanalysis, the LF/LG group was split into two groups: "paradoxical" (P-LF/LG; ejection fraction > 50%) and "classical" LF/LG (C-LF/LG; ejection fraction < 50%). Follow-up echocardiography was performed in patients with severe AS after 3.3 ± 1.7 years. Survival status was ascertained after 5.0 ± 2.0 years. Coronary artery disease was more frequent in LG/AS than HG/AS patients. Already at baseline, LF/LG patients showed reduced left ventricular global systolic strain and reduced systemic arterial compliance compared with HG/AS patients (HG/AS, 1.0 ± 0.4 mL · mm Hg-(1) · m(-2); NF/LG, 0.9 ± 0.2 mL · mm Hg-(1) · m(-2); LF/LG, 0.6 ± 0.2 mL · mm Hg(-1) · m(-2); P < .001). The initially elevated valvuloarterial impedance increased significantly more in LG/AS than in the other groups (HG/AS, 2.2 ± 0.9 mm Hg · mL-(1) · m(-2); NF/LG, 2.2 ± 0.5 mm Hg · mL-(1) · m(-2); LF/LG, 3.2 ± 0.8 mm Hg · mL(-1) · m-(2); P < .001), while aortic valve area decreased by 42% in HG/AS versus 34% in NF/LG and 32% in LF/LG (P < .001). At follow-up, global systolic strain was significantly reduced in C-LF/LG (7.7 ± 2.5 vs 13.5 ± 2.9 in P-LF/LG, P < .001). In P-LF/LG, mitral E/E' ratio increased significantly from 8.9 ± 4.0 to 26.4 ± 9.2 (P < .05). In patients with AS with high-gradient physiology, the valve constitutes the primary problem. By contrast, low-gradient AS is a systemic disease with valvular, vascular, and myocardial components, resulting in a slower progression of transvalvular gradient, but worse clinical outcome. In C-LF/LG, impaired systolic function leads to an LG flow pattern, whereas the pathophysiology in P-LF/LG is predominantly a diastolic dysfunction.

Cutaneous gangrene secondary to focal thrombosis--an important cutaneous manifestation of ulcerative colitis. We describe a patient who developed cutaneous gangrene secondary to microvascular thrombosis, an uncommon complication of inflammatory bowel disease with potentially serious manifestations.

Assessment of osteoporotic vertebral fractures using specialized workflow software for 6-point morphometry. To evaluate the time required, the accuracy and the precision of a model-based image analysis software tool for the diagnosis of osteoporotic fractures using a 6-point morphometry protocol. Lateral dorsal and lumbar radiographs were performed on 92 elderly women (mean age 69.2+/-5.7 years). Institutional review board approval and patient informed consent were obtained for all subjects. The semi-automated and the manual correct annotations of 6-point placement were compared to calculate the time consumed and the accuracy of the software. Twenty test images were randomly selected and the data obtained by multiple perturbed initialisation points on the same image were compared to assess the precision of the system. The time requirement data of the semi-automated system (420+/-67 s) were statistically different (p<0.05) from that of manual placement (900+/-77 s). In the accuracy test, the mean reproducibility error for semi-automatic 6-point placement was 2.50+/-0.72% [95% CI] for the anterior-posterior reference and 2.16+/-0.5% [95% CI] for the superior-inferior reference. In the precision test the mean error resulted averaged over all vertebrae was 2.6+/-1.3% in terms of vertebral width. The technique is time effective, accurate and precise and can, therefore, be recommended in large epidemiological studies and pharmaceutical trials for reporting of osteoporotic vertebral fractures.

No Difference in Dislocation Seen in Anterior Vs Posterior Approach Total Hip Arthroplasty. The direct anterior approach (DAA) for total hip arthroplasty (THA) has rapidly become popular, but there is little consensus regarding the risks and benefits of this approach in comparison with a modern posterior approach (PA). A total of 2147 patients who underwent DAA THA were propensity score matched with patients undergoing PA THA on the basis of age, gender, body mass index, and American Society of Anesthesia classification using data from a state joint replacement registry. Mean age of the matched cohort was 64.8 years, mean body mass index was 29.1 kg/m(2), and 53% were female. Multilevel logistic regression models using generalized estimating equations to control for grouping at the hospital level were used to identify differences in various outcomes. There was no difference in the dislocation rate between patients undergoing DAA (0.84%) and PA (0.79%) THA. Trends indicating a slightly longer length of stay with the PA and a slightly greater risk of fracture, increased blood loss, and hematoma with the DAA are consistent with previous studies. On the basis of short-term outcome and complication data, neither approach has a compelling advantage over each other, including no difference in the dislocation risk.

High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.

A miniaturized wall-climbing segment robot inspired by caterpillar locomotion. Caterpillars are very successful soft-bodied climbers that navigate in complex environments. This paper develops a multi-segmented robot climbing on vertical surfaces using dry adhesive pads, inspired by caterpillar locomotion. The miniaturized robot consists of four segments, and each segment uses a solenoid actuator with a permanent magnet plunger. The head and body segments adapt a novel mechanism and Scott-Russell linkages to generate a bi-directional plane motion using one solenoid actuator, resulting to reliable attaching and peeling motions of gecko pads. A tail is also attached at the back of the last segment to avoid falling or exhibiting unstable motion. Gecko-inspired adhesive pads are fabricated from polydimethylsiloxane (PDMS) with the area of 20 mm × 10 mm. We have conducted experiments on the locomotion performance of the segment robot climbing vertical surfaces for two types of locomotion, achieving the fast and stable climbing motion.

The etiquette of endometriosis: stigmatisation, menstrual concealment and the diagnostic delay. Endometriosis is a chronic gynaecological condition of uncertain aetiology characterised by menstrual irregularities. Several studies have previously identified a lengthy delay experienced by patients between the first onset of symptoms and eventual diagnosis. Various explanations have been advanced for the diagnostic delay, with both doctors and women being implicated. Such explanations include that doctors normalise women's menstrual pain and that women might delay in seeking medical advice because they have difficulty distinguishing between 'normal' and 'abnormal' menstruation. It has been suggested that the diagnostic delay could be reduced if women were trained in how to distinguish between 'normal' and 'abnormal' menstrual cycles. In this paper I argue that whilst these may be factors in the diagnostic delay, women's reluctance to disclose problems associated with their menstrual cycle may be a more significant and hitherto neglected factor. I argue women are reluctant to disclose menstrual irregularities because menstruation is a 'discrediting attribute' (Goffman, 1963) and disclosure renders women vulnerable to stigmatisation. Women actively conceal their menstrual irregularities through practices of the 'menstrual etiquette' (Laws, 1990) which involves the strategic concealment of menstrual problems. This argument is supported through an analysis of the experiences of 20 Australian women diagnosed with endometriosis. The ramifications of this analysis for chronic pain conditions more generally and for practical strategies designed to address the endometriosis diagnostic delay are considered.