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1-96.8) than convalescent patients (median 49.1, IQR 20-62; median 52.9, IQR 31.2-76.2). GenScript sVNT is suitable to screen for SARS-CoV-2-neutralizing antibodies; however, to obtain accurate results, confirmatory testing by PRNT in a equivocal area is required. This equivocal area may require adaptation for use in vaccinated individuals, due to higher antibody titers.This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 21 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p  less then  0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22% 74%) and 20% assigned to placebo (95% CI 2% 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Clinical trial registration information Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https//clinicaltrials.gov ; NCT01302964.The nitric oxide-cGMP (NO-cGMP) pathway is of outstanding importance for vascular homeostasis and has multiple beneficial effects in vascular disease. Neointimal hyperplasia after vascular injury is caused by increased proliferation and migration of vascular smooth muscle cells (VSMCs). However, the role of NO-cGMP signaling in human VSMCs in this process is still not fully understood. Here, we investigate the interaction between platelet derived growth factor (PDGF)-signaling, one of the major contributors to neointimal hyperplasia, and the cGMP pathway in vascular smooth muscle, focusing on NO-sensitive soluble guanylyl cyclase (sGC). We show that PDGF reduces sGC expression by activating PI3K and Rac1, which in turn alters Notch ligand signaling. These data are corroborated by gene expression analysis in human atheromas, as well as immunohistological analysis of diseased and injured arteries. Collectively, our data identify the crosstalk between PDGF and NO/sGC signaling pathway in human VSMCs as a potential target to tackle neointimal hyperplasia.

Vegetable and fruit consumption may have a protective effect against several types of cancer. However, evidence suggesting that increased intake of vegetables and fruits, their subtypes, or the antioxidant nutrients they contain in abundance decreases the risk of bladder cancer is limited.

This study included 80,952 participants from the Japan Public Health Center-based Prospective Study, who responded to a food frequency questionnaire in a 5-year follow-up survey in 1995-1998 and were followed up until December 2015 to investigate the associations between intake of vegetables and fruits, their subtypes, or the antioxidant nutrients and bladder cancer risk using Cox proportional hazards regression models.

Within 1,287,514 person-years of follow-up, 401 bladder cancer cases (307 men and 94 women) were diagnosed. No association was found between intake of total vegetable and fruit, total vegetable, total fruit, subtypes of vegetables and fruits, or antioxidant nutrients and bladder cancer risk in both men and women, even in the analyses conducted among men stratified by smoking status.

In this population, the consumption of vegetables and fruits was not associated with the risk of bladder cancer.

In this population, the consumption of vegetables and fruits was not associated with the risk of bladder cancer.There is a strong pressure to reduce nitrogen (N) fertilizer inputs while maintaining or increasing current cereal crop yields. We show that overexpression of TaDWF4-B, the dominant shoot expressed homoeologue of OsDWF4, in wheat can increase plant productivity by up to 105% under a range of N levels on marginal soils, resulting in increased N use efficiency (NUE). We show that a two to four-fold increase in TaDWF4 transcript levels enhances the responsiveness of genes regulated by N. The productivity increases seen were primarily due to the maintenance of photosystem II operating efficiency and carbon assimilation in plants when grown under limiting N conditions and not an overall increase in photosynthesis capacity. The increased biomass production and yield per plant in TaDWF4 OE lines could be linked to modified carbon partitioning and changes in expression pattern of the growth regulator Target Of Rapamycin, offering a route towards breeding for sustained yield and lower N inputs.Amoxicillin is recommended as first-line antibiotic treatment for community-acquired pneumonia, the leading infectious cause of mortality in children aged less than 5 years. We conducted a double-blind, randomized controlled non-inferiority trial comparing 3- to 5-day amoxicillin treatment for non-severe chest-indrawing pneumonia in HIV-negative children aged 2 to 59 months in Malawi. In a secondary analysis, we assessed the frequency of serious adverse events (SAEs) during the trial to evaluate the safety of treatment with amoxicillin. Enrolled children with non-severe chest-indrawing pneumonia were randomized to either 3- or 5-day amoxicillin and followed for 14 days to track clinical outcomes. In addition to evaluation for treatment failure (primary endpoint, day 6), relapse, and study drug adherence, children were assessed for adverse events, including SAEs, which were managed per local standard clinical practice until resolution or stabilization. Between March 2016 and April 2019, 3000 children were enromoxicillin use in children with pneumonia.Clinical trial registration ClinicalTrials.gov (NCT02678195).Sleep is essential for life, including daily cognitive processes, yet the amount of sleep required for optimal brain health as we grow older is unclear. Poor memory and increased risk of dementia is associated with the extremes of sleep quantity and disruption of other sleep characteristics. We examined sleep and cognitive data from the UK Biobank (N = 479,420) in middle-to-late life healthy individuals (age 38-73 years) and the relationship with brain structure in a sub-group (N = 37,553). Seven hours of sleep per day was associated with the highest cognitive performance which decreased for every hour below and above this sleep duration. This quadratic relationship remained present in older individuals (>60 years, N = 212,006). Individuals who sleep between six-to-eight hours had significantly greater grey matter volume in 46 of 139 different brain regions including the orbitofrontal cortex, hippocampi, precentral gyrus, right frontal pole and cerebellar subfields. Several brain regions showed a quadratic relationship between sleep duration and volume while other regions were smaller only in individuals who slept longer. These findings highlight the important relationship between the modifiable lifestyle factor of sleep duration and cognition as well as a widespread association between sleep and structural brain health.Extraction of integral membrane proteins with poly(styrene-co-maleic acid) provides a promising alternative to detergent extraction. A major advantage of extraction using copolymers rather than detergent is the retention of the lipid bilayer around the proteins. Here we report the first functional investigation of the mammalian insulin receptor which was extracted from cell membranes using poly(styrene-co-maleic acid). We found that the copolymer efficiently extracted the insulin receptor from 3T3L1 fibroblast membranes. Surprisingly, activation of the insulin receptor and proximal downstream signalling was detected upon copolymer extraction even in the absence of insulin stimulation. Insulin receptor and IRS1 phosphorylations were above levels measured in the control extracts made with detergents. However, more distal signalling events in the insulin signalling cascade, such as the phosphorylation of Akt were not observed. Following copolymer extraction, in vitro addition of insulin had no further effect on insulin receptor or IRS1 phosphorylation. Therefore, under our experimental conditions, the insulin receptor is not functionally responsive to insulin. This study is the first to investigate receptor tyrosine kinases extracted from mammalian cells using a styrene-maleic acid copolymer and highlights the importance of thorough functional characterisation when using this method of protein extraction.Little attention has been given to the development of remediation strategies for soils polluted with mixture of pollution (metal(loid)s and organic compounds). The present study evaluates the effectiveness of different types of commercial iron nanoparticles (nanoscale zero valent iron (nZVI), bimetallic nZVI-Pd, and nano-magnetite (nFe3O4)), for the remediation of an industrial soil co-contaminated with Cr and PCBs. Soil samples were mixed with nZVI, nZVI-Pd, or nFe3O4 at doses selected according to their reactivity with PCBs, homogenized, saturated with water and incubated at controlled conditions for 15, 45 and 70 days. For each sampling time, PCBs and chromium were analyzed in aqueous and soil fractions. Cr(VI) and Cr leachability (TCLP test) were determined in the soil samples. The treatment with the three types of iron nanoparticles showed significant reduction in Cr concentration in aqueous extracts at the three sampling times (> 98%), compared to the control samples. The leachability of Cr in treated soil samples also decreased and was stable throughout the experiment. Results suggested that nZVI and nZVI-Pd immobilized Cr through adsorption of Cr(VI) on the shell and reduction to Cr(III). The mechanism of interaction of nFe3O4 and Cr(VI) included adsorption and reduction although its reducing character was lower than those of ZVI nanoparticles. PCBs significantly decreased in soil samples (up to 68%), after 15 days of treatment with the three types of nanoparticles. However, nFe3O4 evidenced reversible adsorption of PCBs after 45 days. In general, nZVI-Pd reduced PCB concentration in soil faster than nZVI. Control soils showed a similar reduction in PCBs concentration as those obtained with nZVI and nZVI-Pd after a longer time (45 days). This is likely due to natural bioremediation, although it was not effective for Cr remediation. Results suggest that the addition of nZVI or nZVI-Pd and pseudo-anaerobic conditions could be used for the recovery of soil co-contaminated with Cr and PCBs.

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