Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells

In the present study, we describe the potential role of melatonin, a pineal hormone, in regulating the activation of the antigen-specific T cell response. Melatonin encouraged the proliferation of Th cells and improved their ability to secrete IL-4, but down-regulated the levels of IL-2 and interferon-gamma (IFN-γ). Melatonin, however, could not exert any influence on the T cells of unprimed mice. On studying the regulation of subclass of IgG isotype, melatonin specifically enhanced the secretion of antigen-specific IgG1 antibodies and decreased the yield of IgG2a isotype. The results suggest that melatonin possibly acts by selectively activating a Th2-like immune response.     

P-selectin inhibition suppresses muscle regeneration following injury

This investigation sought to determine if P-selectin-mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P-selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 microg/mouse or with 100 microl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post-injury by the highest dose of sPSGL-1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 microg anti-P-selectin or isotype-control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post-injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype-injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P-selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.     

Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.      

Chondral separation in the trochlear groove - a definite clinical entity

Four patients with unusual femoro-patellar chondral defects are presented. We were unable to find their particular lesion described adequately in the literature. The patients all gave a history of relatively minor non-contact injury and presented with anterior knee pain and persistent swelling. The main features on clinical examination were moderate effusion and marked patello-femoral crepitus. Plain X-rays of the knee were unhelpful. At arthroscopy large full thickness chondral defects were seen on the femoral side of the patello-femoral articulation at the site of patellar contact with the knee in about 60° of flexion. The synovium was found to be prolific and vascular. Multiple 1.6-mm drill holes were made in the defect and chondral debris was washed out. Two patients underwent associated lateral patellar release. When a clear cut mechanical patello-femoral disorder presents unexpectedly with associated effusion and a normal radiograph, we suggest that arthroscopy be advised with particular attention to the femoral trochlea.     

Studies with {α 2}-adrenoceptor agonists and alcohol abstinence syndrome in rats

Various ₂-adrenoceptor agonists were assessed for their effects on alcohol abstinence syndrome in rats. In the first experimental model, groups of Wistar rats were made alcohol dependent by feeding alcohol together with sweetened milk for 15 days. The volume of fluid intake was measured every 12 h to determine daily ethanol consumption. Abstinence signs following abrupt alcohol withdrawal were observed in control as well as test groups receiving various ₂-adrenoceptor agonists. Clonidine, guanfacine and B-HT 920, in equimolar concentration (0.5 M/kg), effectively attenuated the various abstinence signs, which developed after alcohol withdrawal. In the other experimental model, rats were subjected to cold water immersion to induce wet shakes. The inhibitory action of ₂-adrenoceptor agonists was assessed in this test model. Clonidine, guanfacine and B-HT 920 markedly suppressed the cold water immersion-induced wet shakes and pretreatment with yohimbine (0.1 and 2.0 M/kg) reversed this inhibitory effect. The present data reveal the possible therapeutic potential of ₂-adrenoceptor agonists in alleviating alcohol abstinence syndrome, and suggest that the resultant reduced noradrenergic activity may be responsible for the beneficial action.     

Sex in the Era of COVID-19 in a U.S. National Cohort of Cisgender Men,Transgender Women,and Transgender Men Who Have Sex with Men: April–May 2020

Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n?=?3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β?=?0.90, 95% CI 0.40–1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR?=?1.21), being Black (AOR?=?1.79) or Latinx (AOR?=?1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR?=?1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19.