Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle

Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle

CARROT YIELD AND RECOVERY EFFICIENCY OF NITROGEN, PHOSPHORUS AND POTASSIUM

The objective of this work was to evaluate the carrot crop recovery efficiency of nitrogen, phosphorus and potassium from fertilizers. Two experiments were conducted in an experimental area in Rio Paranaiba - MG. The cultivar („Juliana‟) was sown during the summer period and the cultivar „Nayarit‟ during the winter period. In both experiments, the treatments consisted of six fertilization combinations of N, P 2 O, K 2 O (kg ha - 1 ): fertilization without N (0 - 500 - 450), without P (100 - 0 - 450), without K (100 - 500 - 0), standard (100 - 500 - 450), higher than standard (100 - 700 - 600) and lower than standard (100 - 300 - 300). The harvest was carried out when most of the roots presented commercial standard well accepted by the consumers. The fresh and dry matter of roots and leaves were quantified, and the yield was calculated based on the fresh matter. The analysis of N, P and K contents in leaves and roots were carried out by harvest time, and the nutrients absorption and exportation were determined based on these contents and on the dry matter of roots and leaves. N, P and K omissions reduced the yield of the cultivar „Juliana‟. For the cultivar „Nayarit‟, only P omission reduced and P and K fertilizations increased the yield. The cultivar „Nayarity‟, which is more productive than „Juliana”, absorbed more quantities of N, P and K. Carrot recovery efficiency of nitrogen, phosphorus and potassium is low

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Health Effects of Overweight and Obesity in 195 Countries over 25 Years

BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015. RESULTS: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease. CONCLUSIONS: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.

Avoiding Surgical Skill Decay:A Systematic Review on the Spacing of Training Sessions

OBJECTIVE: Spreading training sessions over time instead of training in just 1 session leads to an improvement of long-term retention for factual knowledge. However, it is not clear whether this would also apply to surgical skills. Thus, we performed a systematic review to find out whether spacing training sessions would also improve long-term retention of surgical skills. DESIGN: We searched the Medline, PsycINFO, Embase, Eric, and Web of Science online databases. We only included articles that were randomized trials with a sample of medical trainees acquiring surgical motor skills in which the spacing effect was reported. The quality and bias of the articles were assessed using the Cochrane Collaboration's risk of bias assessment tool. RESULTS: With respect to the spacing effect, 1955 articles were retrieved. After removing duplicates and articles that did not meet the inclusion criteria, 11 articles remained. The overall quality of the experiments was "moderate." Trainees in the spaced condition scored higher in a retention test than students in the massed condition. CONCLUSIONS: Our systematic review showed evidence that spacing training sessions improves long-term surgical skills retention when compared to massed practice. However, the optimal gap between the re-study sessions is unclear

Development of cognitive processing and judgments of knowledge in medical students: Analysis of progress test results

BACKGROUND: Beside acquiring knowledge, medical students should also develop the ability to apply and reflect on it, requiring higher-order cognitive processing. Ideally, students should have reached higher-order cognitive processing when they enter the clinical program. Whether this is the case, is unknown. We investigated students' cognitive processing, and awareness of their knowledge during medical school. METHODS: Data were gathered from 347 first-year preclinical and 196 first-year clinical students concerning the 2008 and 2011 Dutch progress tests. Questions were classified based upon Bloom's taxonomy: "simple questions" requiring lower and "vignette questions" requiring higher-order cognitive processing. Subsequently, we compared students' performance and awareness of their knowledge in 2008 to that in 2011 for each question type. RESULTS: Students' performance on each type of question increased as students progressed. Preclinical and first-year clinical students performed better on simple questions than on vignette questions. Third-year clinical students performed better on vignette questions than on simple questions. The accuracy of students' judgment of knowledge decreased over time. CONCLUSIONS: The progress test is a useful tool to assess students' cognitive processing and awareness of their knowledge. At the end of medical school, students achieved higher-order cognitive processing but their awareness of their knowledge had decreased

La Toilette. Almanach des femmes pour 1843, par Eugène Briffault. 1er [sic] année...

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