Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of an association between environmental exposure to polychlorinated biphenyls and p,p'-DDE and DNA damage in human sperm measured using the neutral comet assay.

BACKGROUND Chlorinated organic chemicals, such as polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), dichlorodiphenyl trichloroethane (DDT), and dichlorodiphenyl dichloroethene (DDE, the most stable daughter compound of DDT) are persistent lipophilic compounds found in a large portion of the general population. To explore the hypothesis that environmental exposure to these compounds is associated with altered DNA integrity in human sperm, a study of 212 male partners of a sub-fertile couple who presented to the Massachusetts General Hospital Andrology Laboratory was conducted. METHODS The neutral single cell microgel electrophoresis assay (comet assay) was used to assess DNA integrity in sperm. VisComet image analysis software was used to measure total comet length, the proportion of DNA present in the comet tail, and tail distributed moment, an integrated measure of length and intensity. RESULTS In the regression analyses, there were no statistically significant consistent associations between the comet assay parameters and any of the individual PCB congeners, sum of PCB, or p,p'-DDE. CONCLUSION These results suggest that there are not strong relationships between adult levels of these chlorinated organic compounds and sperm DNA damage as measured by the comet assay.
Impact of restarting warfarin therapy in renal disease anticoagulated patients with gastrointestinal hemorrhage

Abstract Background: Atrial fibrillation (AF) is emerging as a major health problem. The prevalence is as high as 32% in patients with renal disease. Gastrointestinal bleeding (GIB) is a frequent complication. Objective: To investigate the hazards of resumption or discontinuation of anticoagulation in renal disease patients after an episode of GIB. Design, settings, participants and measurements: This is a multicenter retrospective cohort of patients with AF on warfarin that developed an episode of GIB. Chronic kidney disease (CKD) was defined by eGFR ≤60 mL/min and end stage renal disease (ESRD) was defined by being on hemodialysis for >3 months. Outcomes were 90-day recurrent gastrointestinal bleeding (GIB), mortality, and stroke/transient ischemic attack (TIA). Results: Out of 11,513 AF patients, index GIB occurred in 96 ESRD and 159 CKD patients. Outcomes of CKD patients did not differ when compared with patients with normal kidney function. CKD patients who resumed warfarin had decreased stroke/TIA rates (p < 0.0001). There were no significant differences between CKD patients who resumed warfarin versus that did not resume warfarin (p > 0.05). ESRD patients also did not have significant differences in outcomes when compared to patients with normal kidney function restarted on warfarin. However, there was an increase in recurrent GIB and decrease in mortality as well as stroke/TIA when patients with ESRD that restarted warfarin were compared with ESRD patients who did not restart warfarin. Conclusion: Study suggests resuming warfarin after an episode of GIB in CKD patients but recommends considering the increased risk of recurrent GIB in ESRD patients.
Transport and Pharmacological Properties of Nine Different Human Na,K-ATPase Isozymes*

Na,K-ATPase plays a crucial role in cellular ion homeostasis and is the pharmacological receptor for digitalis in man. Nine different human Na,K-ATPase isozymes, composed of 3 α and β isoforms, were expressed in Xenopus oocytes and were analyzed for their transport and pharmacological properties. According to ouabain binding and K+-activated pump current measurements, all human isozymes are functional but differ in their turnover rates depending on the α isoform. On the other hand, variations in external K+ activation are determined by a cooperative interaction mechanism between α and β isoforms with α2-β2 complexes having the lowest apparent K+ affinity. α Isoforms influence the apparent internal Na+ affinity in the order α1 > α2 > α3 and the voltage dependence in the order α2 > α1 > α3. All human Na,K-ATPase isozymes have a similar, high affinity for ouabain. However, α2-β isozymes exhibit more rapid ouabain association as well as dissociation rate constants than α1-β and α3-β isozymes. Finally, isoform-specific differences exist in the K+/ouabain antagonism which may protect α1 but not α2 or α3 from digitalis inhibition at physiological K+ levels. In conclusion, our study reveals several new functional characteristics of human Na,K-ATPase isozymes which help to better understand their role in ion homeostasis in different tissues and in digitalis action and toxicity.
Automated podcasting system for universities

This paper presents the results achieved at Graz University of Technology (TU Graz) in the field of automating the process of recording and publishing university lectures in a very new way. It outlines cornerstones of the development and integration of an automated recording system such as the lecture hall setup, the recording hardware and software architecture as well as the development of a text-based search for the final product by method of indexing video podcasts. Furthermore, the paper takes a look at didactical aspects, evaluations done in this context and future outlook.
Iron status of children with short stature during accelerated growth due to growth hormone treatment

We determined the influence of human growth hormone (hGH) treatment on blood soluble transferrin receptor (sTfR) in 35 children with short stature. Whereas the serum concentration of ferritin decreased from 29.6 μg/1 to 19.7 μg/l, and that of transferrin increased from 2.9g/1 to 3.2g/1 during 6 months (p < 0.001), only a minimum rise in the sTfR concentration was observed (7.12 ± 0.20mg/1 vs 7.51 ± 0.19mg/l, p= 0.025). The prevalence of anaemia or microcytosis did not increase. Most of the changes in serum ferritin and transferrin concentrations occurred during the first week. The study demonstrates that rapid body growth per se does not affect the sTfR concentration, but it may affect the serum transferrin and ferritin concentrations. Alternatively, GH may have a specific effect on serum ferritin and transferrin concentrations.
Plasmin Induces Local Thrombolysis without Causing Hemorrhage: A Comparison with Tissue Plasminogen Activator in the Rabbit

Summary The direct fibrinolytic enzyme, plasmin, was compared with tissue plasminogen activator (TPA) in rabbit models of local thrombolysis and fibrinolytic hemorrhage. Plasmin was produced by solid-phase urokinase activation of plasminogen and purified on benzamidine Sepharose. Applied as an intra-arterial infusion into the thrombosed abdominal aorta under conditions of unimpeded blood flow, plasmin (4 mg/kg) and TPA (2 mg/kg) achieved equivalent clot dissolution and flow restoration. Using the model of restricted blood flow into the thrombosed aorta, which limits local plasminogen supply, plasmin was superior to TPA in clot lysis and vascular reperfusion. Using similar dosages of plasmin (2 or 4 mg/kg) and TPA (1 or 2 mg/kg) in the earpuncture rebleed model. TPA induced rebleeding in a dose-dependent manner from prior puncture sites in 9 of 10 animals, while none of the 10 animals exposed to plasmin rebled from these sites. These results suggest that plasmin is an effective, unique thrombolytic agent, distinguished from the plasminogen activators in current usage by its striking safety profile.
Comparative Benefits and Harms of Second-Generation Antidepressants for Treating Major Depressive Disorder

BACKGROUND Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory. PURPOSE To compare the benefits and harms of second-generation antidepressants for treating MDD in adults. DATA SOURCES English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature. STUDY SELECTION 2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm. DATA EXTRACTION Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings. DATA SYNTHESIS Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life. LIMITATIONS Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited. CONCLUSION Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.
Syncytial Heterogeneity as a Mechanism Underlying Cardiac Far‐Field Stimulation During Defibrillation‐Level Shocks

Far‐Field Stimulation via Syncytial Heterogeneities. Introduction: The mechanisms by which a defibrillation shock directly stimulates regions of cardiac tissue distal to the stimulus electrodes (“far‐field” stimulation) are still not well understood. Existing hypotheses have proposed that intercellular discontinuities and/or fiber curvatures induce the requisite membrane polarizations. This article hypothesizes a third potential mechanism: one based on the existence and influences of syncytial (anatomic) heterogeneities inherent throughout the bulk myocardium itself.
Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis*

ObjectiveTo determine the precise relationship among tissue factor, tissue factor pathway inhibitor (TFPI), and neutrophil elastase in sepsis, as well as to test the hypothesis that low TFPI concentrations are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome and death. DesignProspective, cohort study. SettingGeneral intensive care unit of tertiary care emergency department. PatientsThirty-one consecutive patients with sepsis, classified as 15 survivors and 16 nonsurvivors. Ten normal, healthy volunteers served as controls. InterventionsNone. Measurements and Main ResultsTissue factor antigen concentration (tissue factor), TFPI, neutrophil elastase, and global variables of coagulation and fibrinolysis were measured on the day of diagnosis of sepsis, severe sepsis, and septic shock and days on 1–4 after diagnosis. The number of systemic inflammatory response syndrome criteria that patients met and the disseminated intravascular coagulation score were determined simultaneously. The results of these measurements were compared between the survivors and the nonsurvivors. In the nonsurvivors, significantly higher concentrations of tissue factor and neutrophil elastase were found compared with the survivors and control subjects. However, the TFPI values showed no difference between the two groups. No correlation was found between the peak concentrations of tissue factor and TFPI. Disseminated intravascular coagulation scores and numbers of the SIRS criteria met by the survivors significantly decreased from day 0 to day 4, but those of the nonsurvivors did not improve during the study period. The nonsurvivors showed thrombocytopenia and higher numbers of dysfunctioning organs than did the survivors. ConclusionsWe systematically elucidated the relationship between tissue factor and TFPI in patients with sepsis, severe sepsis, and septic shock. Activation of tissue factor-dependent coagulation pathway not adequately balanced by TFPI has important roles in sustaining DIC and systemic inflammatory response syndrome, and it contributes to multiple organ dysfunction syndrome and death. High concentrations of neutrophil elastase released from activated neutrophils may explain, in part, the imbalance of tissue factor and TFPI in sepsis.
Cell cycle checkpoints and their impact on anticancer therapeutic strategies

Cells contain numerous pathways designed to protect them from the genomic instability or toxicity that can result when their DNA is damaged. The p53 tumor suppressor is particularly important for regulating passage through G1 phase of the cell cycle, while other checkpoint regulators are important for arrest in S and G2 phase. Tumor cells often exhibit defects in these checkpoint proteins, which can lead to hypersensitivity; proteins in this class include ataxia–telangiectasia mutatated (ATM), Meiotic recanbination 11 (Mre11), Nijmegen breakage syndrome 1 (Nbs 1), breast cancer susceptibility genes 1 and 2 (BRCA1), and (BRCA2). Consequently, tumors should be assessed for these specific defects, and specific therapy prescribed that has high probability of inducing response. Tumors defective in p53 are frequently considered resistant to apoptosis, yet this defect also provides an opportunity for targeted therapy. When their DNA is damaged, p53‐defective tumor cells preferentially arrest in S or G2 phase where they are susceptible to checkpoint inhibitors such as caffeine and UCN‐01. These inhibitors preferentially abrogate cell cycle arrest in p53‐defective cells, driving them through a lethal mitosis. Wild type p53 can prevent abrogation of arrest by elevating levels of p21waf1 and decreasing levels of cyclins A and B. During tumorigenesis, tumor cells frequently loose checkpoint controls and this facilitates the development of the tumor. However, these defects also represent an Achilles heel that can be targeted to improve current therapeutic strategies. © 2003 Wiley‐Liss, Inc.
Results from Ireland's 2014 Report Card on Physical Activity in Children and Youth.

BACKGROUND Physical activity (PA) levels are a key performance indicator for policy documents in Ireland. The first Ireland Report Card on Physical Activity in Children and Youth aims to set a robust baseline for future surveillance of indicators related to PA in children and youth. METHODS Data collected between 2003-2010 on more than 35,000 7- to 18-year-old children and youth were used and graded using a standardized grading system for 10 indicators. RESULTS Grades assigned for the indicators were as follows: overall physical activity levels, D-; sedentary behavior (TV viewing), C-; organized sport participation, C-: physical education, D-; active play, inconclusive (INC); active transportation, D; school, C-, community and the built environment, B; family, INC; and government, INC. CONCLUSIONS PA recommendations exist in Ireland but this Report Card has shown that participation is still low. A number of promising policies, programs and services are in place but these require thorough evaluation and adequate resourcing. Agreement and implementation of a common framework for the systematic surveillance of indictors related to PA of children and youth is necessary to monitor change over time and ensure the impact of promising work is captured.
Morphological properties of chick retinal ganglion cells in relation to their central projections

Morphological properties of chick retinal ganglion cells (RGCs) were studied in relation to their central projections in 23 chicks. A total of 217 RGCs were retrogradely labeled by applying a carbocyanine dye (DiI) to the thalamus and optic tectum. The labeled RGCs were classified into six groups on the basis of their somal areas, dendritic fields, and branching patterns. The dendrites of these RGCs extended horizontally in the inner plexiform layer (IPL) forming eight dendritic strata. The RGCs in each group showed certain specificities in their central projections. Group Ic predominantly projected to the tectum. Groups IIs and IIIs showed a high thalamic dominance. Groups Is and IIc were nonspecific with regard to their tectal and thalamic projections. Group IVc showed tectal‐specific projections. Occurrence rates of the dendritic strata increased progressively toward the inner part of the IPL, i.e., DSs (dendritic strata) 1–4 were scantily distributed, DSs 5 and 6 were moderately distributed, and DSs 7 and 8 were the most frequently distributed. A total of 42 dendritic stratification patterns were identified, and of these, 18 patterns were common to the tectal RGCs (tec‐RGCs) and thalamic RGCs (tha‐RGCs). The common patterns were detected very frequently in the tec‐ and tha‐RGCs (≈85%), and the dendritic strata were largely distributed in the inner part of the IPL (DSs 5–8). In contrast, the remaining 24 noncommon stratification patterns showed low occurrence rates (≈15%); however, these dendritic strata were widely distributed in both the outer (DSs 1–4) and inner (DSs 5–8) IPL. J. Comp. Neurol. 514:117–130, 2009. © 2009 Wiley‐Liss, Inc.
Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation

We have investigated the effect of a 50% reduction in maternal nutrient intake during the last 30 days of pregnancy on arterial blood pressure and on arterial blood pressure responses to angiotensin II (AII) and the angiotensin converting enzyme (ACE) inhibitor captopril in the sheep fetus at 115–125 and at 135–145 days gestation (term = 147 ± 3 days gestation). Fetal plasma glucose concentrations were lower in the undernourished (UN) group compared to the control animals. There was no difference, however, in fetal plasma cortisol or adrenocorticotrophic hormone (ACTH) concentrations between the UN and control groups between 115 and 145 days gestation. During the first 10 days of undernutrition, maternal plasma concentrations of cortisol were increased in the UN group compared to controls. At 115–125 days gestation, fetal arterial blood pressure was also higher in the UN group compared with controls and there was an inverse relationship (r=−0.62, P < 0.05) between mean arterial pressure and the fetal plasma concentrations of ACTH in the UN group. Fetal blood pressure responses to increasing doses of angiotensin II were also higher (P < 0.05) in UN compared to control animals at 115–125 days gestation. Between 135 and 145 days gestation, fetal arterial blood pressure was increased in UN fetal sheep and mean arterial blood pressure was correlated with fetal plasma concentrations of cortisol. Increased arterial blood pressure and responsiveness to AII measured in the fetuses of nutrient‐restricted ewes may be related in part to fetal exposure to the actions of cortisol derived from transplacental transfer during the first 10 days after the start of the restricted feeding regime.
Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer.

PURPOSE To determine the antitumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr), in previously treated patients with metastatic renal cell carcinoma, and to characterize its toxicity, immunogenicity, pharmacokinetics, and pharmacodynamics. PATIENTS AND METHODS The antitumor activity, as well as the toxicity, pharmacokinetics, pharmacodynamics, and immunogenicity of ABX-EGF, were assessed. RESULTS Eighty-eight patients were treated with ABX-EGF doses of 1.0, 1.5, 2.0, or 2.5 mg/kg weekly with no loading dose. EGFr immunostaining was performed on 76 tumor biopsy specimens (86%), and 69 (91%) scored positive. Major responses occurred in three patients, and two patients had minor responses. Forty-four patients (50%) also had stable disease at their first 8-week assessment, and the median progression-free survival (PFS) was 100 days (95% CI, 58 to 140 days). Low hemoglobin and high alkaline phosphatase predicted for short PFS. The principal toxicity, an acneiform rash, occurred in 68%, 95%, 87%, and 100% of patients who received at least three doses of ABX-EGF at 1.0, 1.5, 2.0, and 2.5 mg/kg/wk, respectively. A trend indicated that the severity of the rash may relate to PFS. No human antihuman antibodies were detected. ABX-EGF pharmacokinetics fit a model that incorporated both linear and saturable EGFr-mediated clearance mechanisms, and interindividual variability was low. At 2.5 mg/kg/wk, ABX-EGF concentrations throughout treatment exceeded those estimated to saturate nonlinear clearance and inhibit xenograft growth by 90%. CONCLUSION ABX-EGF was generally well tolerated. The objective response rate was low in previously treated patients with metastatic renal cell carcinoma. Although skin rash may be a pharmacodynamic marker of drug action, its potential as a surrogate marker of clinical benefit requires further evaluation.
Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis.

BACKGROUND Given the current lack of effective vaccines against TB, the accuracy of screening tests for determining or excluding latent TB infection (LTBI) is decisive in effective TB control. This meta-analysis critically appraises studies investigating the positive and the negative predictive value (PPV and NPV, respectively) from a test-determined LTBI state for progression to active TB of interferon-γ release assays (IGRAs) and the tuberculin skin test (TST). METHODS We searched MEDLINE, EMBASE, and Cochrane bibliographies for relevant articles. After qualitative evaluation, the PPV and NPV for progression of commercial and “in-house” IGRAs and the TST for persons not receiving preventive treatment in the context of the respective IGRA studies were pooled using both a fixed and a random-effect model. Weighted rates were calculated for all study populations and for groups solely at high risk of TB development. RESULTS The pooled PPV for progression for all studies using commercial IGRAs was 2.7% (95% CI, 2.3%-3.2%) compared with 1.5% (95% CI, 1.2%-1.7%) for the TST (P < .0001). PPV increased to 6.8% (95% CI, 5.6%-8.3%) and 2.4% (95% CI, 1.9%-2.9%) for the IGRAs and the TST, respectively, when only high-risk groups were considered (P < .0001). Pooled values of NPV for progression for both IGRAs and the TST were very high, at 99.7% (95% CI, 99.5%-99.8%) and 99.4% (95% CI, 99.2%-99.5%), respectively, although they were significantly higher for IGRAs (P < .01). CONCLUSIONS Commercial IGRAs have a higher PPV and NPV for progression to active TB compared with those of the TST, especially when performed in high-risk persons.
Acetylcholinesterase mutants in drosophila and their effects on the structure and function of the cental nervous system

Mutations that eliminate acetylcholinesterase (AChE) activity were used to study the effects of disrupted acetylcholine metabolism on the form and function of the central nervous system in Drosophila melanogaster. Mutants in the Ace gene, which have no AChE activity, usually die in early development, but the postembryonic effects of this lesion can be studied in genetic mosaics, or with conditional mutants.