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This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5'-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19-associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.Controlled human infection (CHI) models for the novel coronavirus (SARS-CoV-2) have been proposed as a tool to accelerate the development of vaccines and drugs. Such models carry inherent risks. Participants may develop severe disease or complications after deliberate infection. Prolonged isolation may negatively impact their wellbeing. Through secondary infection of study personnel or participant household contacts, the experimental virus strain may cause a community outbreak. We identified risks associated with such a SARS-CoV-2 CHI model and assessed their likelihood and impact and propose strategies that mitigate these risks. In this report, we show that risks can be minimized with proper risk mitigation strategies; the residual risk however should be weighed carefully against the scientific and social values of such a CHI model.

Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation.

Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2weeks (once daily) 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1week, 1month, and 3months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory.

Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P<0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings.

Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. SR59230A datasheet These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.

Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.

To characterize the extent to which brief cognitive assessments administered in the population-representative US Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct.

Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N=155,690), including the US HRS and selected International Partner Studies. We used the time point of first cognitive assessment for each study to minimize differential practice effects across studies, and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single factor general cognitive function models, and bifactor models representing memory-specific and non-memory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies.

Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single factor general cognitive function models. The data fit the models at reasonable thresholds for single factor models in six of the 12 studies, and for the bifactor models in all 12 of the 12 studies.

The cognitive assessments in the US HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.

The cognitive assessments in the US HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.