Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnea stagnalis Exposed to Different Endocrine Disrupting Chemicals

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 μg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant evidence of interaction of EDCs with reproductive pathways that are under the control of the endocrine system of L. stagnalis

Sensitivity to biases of case-control studies on medical procedures, particularly surgery and blood transfusion, and risk of Creutzfeldt-Jakob disease

BACKGROUND: <br/> Evidence of risk of Creutzfeldt-Jakob disease (CJD) associated with medical procedures, including surgery and blood transfusion, is limited by susceptibility to bias in epidemiological studies.<br/> METHODS: <br/> Sensitivity to bias was explored using a central-birth-cohort model using data from 18 case-control studies obtained after a review of 494 reports on medical procedures and risk of CJD, systematic for the period January 1, 1989 to December 31, 2011. <br/>RESULTS:<br/> The validity of the findings in these studies may have been undermined by: recall; control selection; exposure assessment in life-time periods of different duration, out of time-at-risk of effect, or asymmetry in case/control data; and confounding by concomitant blood transfusion at the time of surgery. For sporadic CJD (sCJD), a history of surgery or blood transfusion was associated with risk in some, but not all, recent studies at a ≥10 year lag time, when controls were longitudinally sampled. Space-time aggregation of surgical events was not seen. Surgery at early clinical onset might be overrepresented among cases. Neither surgical history nor blood transfusion unlabelled for donor status, dental treatments or endoscopic examinations were linked to variant CJD (vCJD).<br/> CONCLUSIONS:<br/> These results indicate the need for further research. Common challenges within these studies include access to and content of past medical/dental treatment records for diseases with long incubation periods

Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis

Updates on the risk factors for latent tuberculosis reactivation and their managements

The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV-infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P &lt; 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D

A review of the anthropometric characteristics, grading and dispensation of junior and youth rugby union players in Australia

The grading of Australian junior and youth rugby union players has received substantial media attention in recent years. Media reports have focussed on size mismatches observed between players, especially players with Polynesian heritage, and the concerned parents who fear for the safety of their child owing to perceived mismatches. Although such concerns are well meaning, few media reports recognise the need for substantial evidence to determine the best grading system for junior and youth rugby union players. The current study reviewed relevant literature pertinent to the grading and dispensation of junior and youth rugby union players. Using primary and secondary search strategies, a total of 33 articles reporting the anthropometric characteristics of junior and youth rugby players were identified. Anthropometric data from the literature were compared with normative population data and currently used dispensation criteria. Junior and youth rugby players were found to be taller and heavier than normative population data. Current dispensation criteria, in terms of body mass, were found to vary and it is suggested that criteria be revised and standardised across rugby unions throughout Australia. Although it is acknowledged that other factors are important for grading players, anthropometric characteristics should be considered as potential dispensation criteria to supplement current age-based grading for junior and youth rugby union players. Measuring the body mass and stature of each junior player upon pre-season registration is suggested, which would provide data to establish valid dispensation criteria for the following season