Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series.

BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None

Mindfulness-based stress reduction or aerobics exercise for reducing burnout in medical residents- a study protocol for a phase III, open-label, multi-center, randomized controlled trial: The MINDER Collaborative group study

Background and objectives: Burnout results from chronic workplace stress leading to emotional exhaustion, negativity, and decreased professional efficiency. In the healthcare system, this can have consequences like increased medical errors, absenteeism, substance abuse, depression, and suicide among health professionals, adversely affecting patient care. Various individual-directed measures like the mindfulness-based stress reduction program (MBSR), one of the most studied and widely adopted techniques, and physical activity, like aerobics or sports, have shown to be effective against burnout. With this study, we intend to increase awareness regarding this public health issue among the residents and the faculty. Our aim is to define a successful intervention that can be incorporated as a yearly requirement for the completion of residency programs. Methodology: This study will be a phase III, multicentric, open-label, placebo (waiting list) controlled trial. Our sample size will be 720 residents sampled from 6 university hospitals from across the world, randomized into 3 parallel arms (1:1:1 ratio stratified according to site and specialty). Residents, diagnosed with burnout based on baseline Maslach Burnout Inventory score (MBI) and having no prior physical or mental health issues, will be included. The first group will undergo the MBSR program for 8 weeks, the second group will undergo a supervised aerobics program for 8 weeks, and the third group will be put into a waiting list for any of the interventions. The primary outcome will be the change in MBI scores after the intervention. The secondary outcomes will be the change in MBI score 3 months after the intervention, and changes in measures like heart rate, blood pressure, glycated hemoglobin, cortisol levels, quality of sleep and quality of life after the intervention and 3 months later. We also plan to do a subgroup analysis to see the difference based on specialty and gender. Study impact: The residency training period is considered one of the most stressful phases in medical education. Higher rates of burnout are noted in the residents, and this can negatively impact patient care and the progression of their careers. This trial will look at multiple interventions to combat burnout recruiting residents of different specialties in different work environments across the world. We hope to remove the stigma surrounding burnout in the healthcare system. This study will show the short and long term benefits of these interventions and would help us recommend their inclusion in various residency programs

Human T-Cell Lymphotropic Virus Type 1-Infected T Lymphocytes Impair Catabolism and Uptake of Glutamate by Astrocytes via Tax-1 and Tumor Necrosis Factor Alpha

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-α) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-α, as the effect of Tax-1 was abolished by anti-TNF-α antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival