RNA-transfected dendritic cells

Based on their unique ability to stimulate primary immune responses, dendritic cells are the most potent antigen-presenting cells known. This ability stems from the fact that they are very efficient at the uptake and processing of antigen and they express high levels of major histocompatibility complex class I and class II, as well as costimulatory molecules, which are required to prime naive cytotoxic T-cells. Many groups of investigators have tried to take advantage of these features by developing dendritic cell-based vaccines against tumors and infectious diseases. While the basic principle in these studies is the same--dendritic cells pulsed with antigen are used to elicit cytotoxic T-cell responses--the methods used are varied. This is particularly true with respect to the nature of the antigen used and the method of antigen delivery. In this article, we will focus on the use of RNA as a form of antigen with which to load dendritic cells. We will discuss the rationale behind using RNA as an antigen source and will review recent studies in both murine and human settings that use RNA-pulsed dendritic cells as vaccines.     

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.     

Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice

CD4⁺ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RB^highCD4⁺ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RB^lowsubset or with unfractionated CD4⁺ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RB^lowpopulation with the CD45RB^high population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RB^high and CD45RB^lowCD4⁺T cell subsets and that disruption of this mechanism has fatalconsequences.     

Cervical squamous intra-epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India

In view of the dual burden of HIV infection and cervical cancers in India, this study was undertaken to estimate the prevalence of Pap smear abnormalities and human papillomavirus infection among HIV-infected women. Consecutive HIV-infected women attending voluntary counseling testing clinics were enrolled. Written informed consent, demographic information, Pap smears, cervical swabs for HPV typing and a blood sample for CD4+ cell count were collected. Treatment for opportunistic and sexually transmitted infections and reproductive tract infections was provided. Women with Pap smear abnormality were referred for further intervention. Between January 2003 and May 2004, 287 HIV-infected women were enrolled. Pap smear abnormalities were seen in 6.3% women and were more common among women aged 30 and above (P=0.042) and those who had suffered from opportunistic infections (P=0.004). In multivariate analysis, Pap smear abnormalities were associated independently with opportunistic infections (P=0.02, AOR 3.8, 95% CI 1.2--11.5). Of the 100 random cervical specimens screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9--43.1) were positive for HPV 16/18. Of the 122 patients who returned for a follow-up visit, 5 patients (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100 person year of follow-up. In order to prevent thousands of deaths due to cervical cancer in India, there is a need for strengthening the Pap smear screening program and HPV vaccine development.     

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.