Notes

[COVID-19 and stress-related disorders].
01). Sperm viability and motility after thawing significantly improved by broccoli (300 mg/kg) compared to control. Testosterone levels significantly increased by broccoli (300 mg/kg) compared to control and caraway (300 mg/kg). The serum and testicular SOD and CAT activity significantly increased by broccoli (300 mg/kg) compared to other groups (p less then 0.05). MDA and DNA fragmentation levels significantly increased by caraway (200 and 300 mg/kg) compared to others (p less then 0.01). It can be concluded that broccoli extract in a dose-dependent manner than caraway extract could improve serum and testes oxidative biomarkers, testicular structure and function, and sperm quality before and after cryopreservation.HDL and its primary receptor, scavenger receptor class B type I (SR-BI), work together to promote the clearance of excess plasma cholesterol, thereby protecting against atherosclerosis. Human variants of SR-BI have been identified in patients with high HDL-cholesterol levels, and at least one variant has been linked to cardiovascular disease. Therefore, while often regarded as beneficial, very high levels of HDL-cholesterol may result from impaired cholesterol clearance through SR-BI and contribute to cardiovascular risk. In this study, we characterized the function of a rare human variant of SR-BI, resulting in the substitution of arginine-174 with cysteine (R174C), which was previously identified in a heterozygous individual with high levels of HDL-cholesterol. We hypothesized that the R174C-SR-BI variant has impaired cholesterol transport functions, which were assessed in COS-7 cells after transient transfection with full-length WT or R174C-SR-BI. Although R174C-SR-BI was expressed at levels comparable to the WT receptor, HDL binding, cholesteryl hexadecyl ether uptake, free cholesterol efflux, and modulation of membrane cholesterol were disrupted in the presence of R174C-SR-BI. We further examined the role of salt bridges as a potential mechanism for R174C-SR-BI dysfunction. If translatable, this human variant could lead to increased plasma HDL-cholesterol levels, impaired cholesterol clearance, and increased cardiovascular disease risk.Indicators for the measurement of programmes for the primary prevention of HIV are less aligned than indicators for HIV treatment, which results in a high burden of data collection, often without a clear vision for its use. As new evidence becomes available, the opportunity arises to critically evaluate the way countries and global bodies monitor HIV prevention programmes by incorporating emerging data on the strength of the evidence linking various factors with HIV acquisition, and by working to streamline indicators across stakeholders to reduce burdens on health-care systems. Programmes are also using new approaches, such as targeting specific sexual networks that might require non-traditional approaches to measurement. Technological advances can support these new directions and provide opportunities to use real-time analytics and new data sources to more effectively understand and adapt HIV prevention programmes to reflect population movement, risks, and an evolving epidemic.
Rates of suicide among people in prison are elevated compared with people of similar age and sex who are living in the community. Improving assessments and interventions to reduce suicide risk requires updated evidence on risk factors. We aimed to examine risk factors associated with suicide in prisoners.

We did an updated systematic review and meta-analysis of risk factors for suicide among people in prison. We searched five biblographic databases for articles published between Jan 1, 2006, and Aug 13, 2020, and one database for articles published between Jan 1, 1973, and Aug 13, 2020. Eligible studies reported risk factors in individuals who died by suicide while in prison and in controls from the general prison population. Selleckchem AZ 3146 Two reviewers independently extracted data for each study using a standardised form. We calculated random-effects pooled odds ratios (ORs) for the association of suicide with demographical, clinical, criminological, and institutional risk factors, and investigated heterogeneity usingg people in prison. Preventive interventions should target these risk factors and include improved access to evidence-based mental health care. Understanding other factors associated with suicide might improve risk stratification and resource allocation in prison services.

Wellcome Trust, National Institute for Health Research Applied Research Collaboration Oxford and Thames Valley.
Wellcome Trust, National Institute for Health Research Applied Research Collaboration Oxford and Thames Valley.
Primary ciliary dyskinesia (PCD) is a heterogeneous disease with a diverse clinical and genetic spectrum among populations worldwide. Few cases of pediatric PCD have been reported from China.

What are the clinical and genotypic characteristics of children with PCD in China?

Clinical characteristics, laboratory findings, and genetic results obtained for 75 patients with PCD were reviewed retrospectively at a single center in China. Genetic sequencing was conducted using whole-exome screening.

Patient median age at diagnosis was 7.0 years (range, 2 months-14 years). Of 75 patients, 88%(66/75) had chronic wet cough, 77%(58/75) had recurrent sinusitis, 76%(57/75) had bronchiectasis, 40%(30/75) had neonatal respiratory distress, and 28%(21/75) had coexistent asthma. Notably, postinfectious bronchiolitis obliterans (PIBO) as first presentation was found in 8%of children (6/75). Genes with the highest incidence of mutations were DNAH11 (15/51), followed by DNAH5 (9/51), CCDC39 (5/51), DNAH1 (4/51), and CCNO (3/51). Four genes (DNAI1, HEATR2, RSPH9, and DNAAF3) each were respectively found in two patients, and seven genes (CCDC40, LRRC6, SPAG1, RSPH4A, ARMC4, CCDC114, and DNAH14, a novel gene) each were mutated once. No differences in classical clinical features were observed among patients with commonly observed PCD-associated genotypes. However, three of six PIBO patients carried DNAH1 mutations.

Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum.
Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affects tens of millions worldwide; the causes of exertional intolerance are poorly understood. The ME/CFS label overlaps with postural orthostatic tachycardia (POTS) and fibromyalgia, and objective evidence of small fiber neuropathy (SFN) is reported in approximately 50%of POTS and fibromyalgia patients.

Can invasive cardiopulmonary exercise testing (iCPET) and PGP9.5-immunolabeled lower-leg skin biopsies inform the pathophysiology of ME/CFS exertional intolerance and potential relationships with SFN?

We analyzed 1,516 upright invasive iCPETs performed to investigate exertional intolerance. After excluding patients with intrinsic heart or lung disease and selecting those with right atrial pressures (RAP)<6.5mmHg, results from 160 patients meeting ME/CFS criteria who had skin biopsy test results were compared with 36 control subjects. Rest-to-peak changes in cardiac output (Qc) were compared with oxygen uptake (Qc/VO
slope) to identify par. In patients with small-fiber pathology, neuropathic dysregulation causing microvascular dilation may limit exertion by shunting oxygenated blood from capillary beds and reducing cardiac return.
These results identify two types of peripheral neurovascular dysregulation that are biologically plausible contributors to ME/CFS exertional intolerance-depressed Qc from impaired venous return, and impaired peripheral oxygen extraction. In patients with small-fiber pathology, neuropathic dysregulation causing microvascular dilation may limit exertion by shunting oxygenated blood from capillary beds and reducing cardiac return.Natural Killer (NK) cells are lymphocytes that are the first line of defense against malignantly transformed cells, virally infected cells and other stressed cell types. To study the cytolytic function of NK cells in vitro, a cytotoxicity assay is normally conducted against a target cancerous cell line. Current assay methods are typically performed in mixed 2D cocultures with destructive endpoints and low throughput, thereby limiting the scale, time-resolution, and relevance of the assay to in vivo conditions. Here, we evaluated a novel, non-invasive, quantitative image-based cytometry (qIBC) assay for detection of NK-mediated killing of target cells in 2D and 3D environments in vitro and compared its performance to two common flow cytometry- and fluorescence-based cytotoxicity assays. Similar to the other methods evaluated, the qIBC assay allowed for reproducible detection of target cell killing across a range of effector-to-target ratios with reduced variability. The qIBC assay also allowed for detection of NK cytolysis in 3D spheroids, which enabled scalable measurements of cell cytotoxicity in 3D models. Our findings suggest that quantitative image-based cytometry would be suitable for rapid, high-throughput screening of NK cytolysis in vitro, including in quasi-3D structures that model tissue environments in vivo.Cancers with hereditary defects in homologous recombination rely on DNA polymerase θ (pol θ) for repair of DNA double-strand breaks. During end joining, pol θ aligns microhomology tracts internal to 5'-resected broken ends. An unidentified nuclease trims the 3' ends before synthesis can occur. Here we report that a nuclease activity, which differs from the proofreading activity often associated with DNA polymerases, is intrinsic to the polymerase domain of pol θ. Like the DNA synthesis activity, the nuclease activity requires conserved metal-binding residues, metal ions, and dNTPs and is inhibited by ddNTPs or chain-terminated DNA. Our data indicate that pol θ repurposes metal ions in the polymerase active site for endonucleolytic cleavage and that the polymerase-active and end-trimming conformations of the enzyme are distinct. We reveal a nimble strategy of substrate processing that allows pol θ to trim or extend DNA depending on the DNA repair context.This study sought to determine differences in preferred messengers on the topic of safe firearm storage and suicide prevention between firearm owners and non-firearm owners, and among firearm owners of different racial groups and sexes. Participants were 6200 United States residents recruited via Qualtrics Panels to complete an online survey. Data were collected during March 2020. The total sample and all subsamples ranked law enforcement, current military personnel, and military veterans as the top three most credible sources to discuss firearm safety for suicide prevention. Significant differences existed among the mean ranking of sources between firearm owners and non-firearm owners as well as between several subgroups of firearm owners. The identical ranking of the top three sources indicates that these groups agree on the relative credibility of multiple sources, although the average level of credibility for particular sources may vary. These findings highlight that the effectiveness of messaging on safe firearm storage may hinge on the identity of the individual delivering the message and provide an initial roadmap for how to consider packaging specific messages.
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