Strongyloides ratti e S. stercoralis: efeitos de cambendazol, tiabendazol e mebendazol in vitro

The effects of in vitro incubation of three henzimidazole anthelmintics, thiabendazole, mebendazole and cambendazole on Strongyloides were compared. No drug affected hatching of S. ratti eggs or the viability of infective larvae or parasitic adult worms, but all three inhibited moulting of S. ratti larvae. In addition, cambendazole, but not thiabendazole or mebendazole, impaired the viability of S. ratti first- and second-stage larvae. The three drugs had no effect on isolated S. stercorais free-living adult worms, but they all prevented development of S. stercoralis rhabditiform larvae. Thiabendazole and mebendazole had no effect on the infectivity of either S. ratti or S. stercoralis infective larvae, but infection with these worms was abrogated by prior incubation with cambendazole. These results indicate that cambendazole acts in a different manner to the other two drugs. Since it is active against larvae migrating through the tissues, it is potentially of much greater value than thiabendazole or mebendazole in the therapy of strongyloidiasis.Os efeitos da incubação de três antihelmínticos, tiabendazol, mebendazol e cambendazol sobre Strongyloides foram comparados. Nenhuma droga afetou a eclosão dos ovos de S. ratti ou a viabilidade de larvas infectantes ou vermes adultos parasitários, mas todas as três inibiram a formação de larvas de S. ratti. Além disso, cambendazol, mas não tiabendazol ou mebendazol, diminuiu a viabilidade de larvas de primeiro e segundo estágio de S. ratti. As três drogas não tiveram efeito sobre vermes adultos de vida livre isolados, de S. stercoralis, mas todas evitaram o desenvolvimento de larvas rabditiformes de S. stercoralis. Tiabenda zol e mebendazol não tiveram efeito sobre a infectividade de larvas infectantes de S. ratti ou de S. stercoralis, mas a infecção com esses vermes foi anulada por incubação prévia com cambendazol. Esses resultados indicam que cambendazol age de modo diferente das outras duas drogas. Uma vez que ele é ativo contra lar vas migrando através dos tecidos, é potencial mente de muito maior valor que o tia bendazol ou mebendazol na terapêutica da esbrongiloidíase

Reliable computational quantification of liver fibrosis is compromised by inherent staining variation

Biopsy remains the gold standard measure for staging liver disease, both to inform prognosis and to assess the response to a given treatment. Semiquantitative scores such as the Ishak fibrosis score are used for evaluation. These scores are utilised in clinical trials, with the US Food and Drug Administration mandating particular scores as inclusion criteria for participants and using the change in score as evidence of treatment efficacy. There is an urgent need for improved, quantitative assessment of liver biopsies to detect small incremental changes in liver architecture over the course of a clinical trial. Artificial intelligence (AI) methods have been proposed as a way to increase the amount of information extracted from a biopsy and to potentially remove bias introduced by manual scoring. We have trained and evaluated an AI tool for measuring the amount of scarring in sections of picrosirius red-stained liver. The AI methodology was compared with both manual scoring and widely available colour space thresholding. Four sequential sections from each case were stained on two separate occasions by two independent clinical laboratories using routine protocols to study the effect of inter- and intra-laboratory staining variation on these tools. Finally, we compared these methods to second harmonic generation (SHG) imaging, a stain-free quantitative measure of collagen. Although AI methods provided a modest improvement over simpler computer-assisted measures, staining variation both within and between labs had a dramatic effect on quantitation, with manual assignment of scar proportion the most consistent. Manual assessment also correlated the most strongly with collagen measured by SHG. In conclusion, results suggest that computational measures of liver scarring from stained sections are compromised by inter- and intra-laboratory staining. Stain-free quantitative measurement using SHG avoids staining-related variation and may prove more accurate in detecting small changes in scarring that may occur in therapeutic trials

Strongyloses ratti and S. stercoralis: effects of cambendazole, thiabendazole and mebendazole in vitro

The effects of in vitro incubation of three henzimidazole anthelmintics, thiabendazole, mebendazole and cambendazole on Strongyloides were compared. No drug affected hatching of S. ratti eggs or the viability of infective larvae or parasitic adult worms, but all three inhibited moulting of S. ratti larvae. In addition, cambendazole, but not thiabendazole or mebendazole, impaired the viability of S. ratti first- and second-stage larvae. The three drugs had no effect on isolated S. stercorais free-living adult worms, but they all prevented development of S. stercoralis rhabditiform larvae. Thiabendazole and mebendazole had no effect on the infectivity of either S. ratti or S. stercoralis infective larvae, but infection with these worms was abrogated by prior incubation with cambendazole. These results indicate that cambendazole acts in a different manner to the other two drugs. Since it is active against larvae migrating through the tissues, it is potentially of much greater value than thiabendazole or mebendazole in the therapy of strongyloidiasis

Prospectus, January 16, 1973

CHAMPAIGN-URBANA PEACE MARCH SCHEDULED; Anti-war resolution proposed; IOC meeting; Parkland trail riders; Please send a picture; Health program enrollment; Financial Board opening; All club treasurers; Can you help?; U.S. Gov\u27t Speaker; Debaters compete at ISU; Cruisin\u27 \u2773; True happenings; Ken\u27s munchy cereal; Equal tyme; Getting ignored by the biggies; PC lady hits the big time; Writer\u27s view questioned; Wanna graduate?; Big Kid\u27s Day?; little fat kid; Population, resources, environment; Mass demonstrations in D.C., Inauguration Day; Chi Gamma Iota; New campus regs; Freed injured; Movie Review: The Getaway; Prof Spectushttps://spark.parkland.edu/prospectus_1973/1014/thumbnail.jp

How should we measure psychological resilience in sport performers?

Psychological resilience is important in sport because athletes must constantly withstand a wide range of pressures to attain and sustain high performance. To advance psychologists’ understanding of this area, there exists an urgent need to develop a sport-specific measure of resilience. The purpose of this paper is to review psychometric issues in resilience research and to discuss the implications for sport psychology. Drawing on the wider general psychology literature to inform the discussion, the narrative is divided into three main sections relating to resilience and its assessment: adversity, positive adaptation, and protective factors. The first section reviews the different ways that adversity has been measured and considers the potential problems of using items with varying degrees of controllability and risk. The second section discusses the different approaches to assessing positive adaptation and examines the issue of circularity pervasive in resilience research. The final section explores the various issues related to the assessment of protective factors drawing directly from current measures of resilience in other psychology sub-disciplines. The commentary concludes with key recommendations for sport psychology researchers seeking to develop a measure of psychological resilience in athletes

Applications of patching to quadratic forms and central simple algebras

This paper provides applications of patching to quadratic forms and central simple algebras over function fields of curves over henselian valued fields. In particular, we use a patching approach to reprove and generalize a recent result of Parimala and Suresh on the u-invariant of p-adic function fields, for p odd. The strategy relies on a local-global principle for homogeneous spaces for rational algebraic groups, combined with local computations.Comment: 48 pages; connectivity now required in the definition of rational group; beginning of Section 4 reorganized; other minor change

Cellular location and activity of Escherichia coli RecG proteins shed light on the function of its structurally unresolved C-terminus

RecG is a DNA translocase encoded by most species of bacteria. The Escherichia coli protein targets branched DNA substrates and drives the unwinding and rewinding of DNA strands. Its ability to remodel replication forks and to genetically interact with PriA protein have led to the idea that it plays an important role in securing faithful genome duplication. Here we report that RecG co-localises with sites of DNA replication and identify conserved arginine and tryptophan residues near its C-terminus that are needed for this localisation. We establish that the extreme C-terminus, which is not resolved in the crystal structure, is vital for DNA unwinding but not for DNA binding. Substituting an alanine for a highly conserved tyrosine near the very end results in a substantial reduction in the ability to unwind replication fork and Holliday junction structures but has no effect on substrate affinity. Deleting or substituting the terminal alanine causes an even greater reduction in unwinding activity, which is somewhat surprising as this residue is not uniformly present in closely related RecG proteins. More significantly, the extreme C-terminal mutations have little effect on localisation. Mutations that do prevent localisation result in only a slight reduction in the capacity for DNA repair. © 2014 The Author(s)

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects