Monkeypox Disease: An Emerging Public Health Concern in the Shadow of COVID-19 Pandemic: An Update.

The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Such outbreaks are a lesson to learn from and seek insight into better disease monitoring and surveillance, thus preventing future outbreaks. Monkeypox, a viral zoonotic illness caused by the monkeypox virus, may no longer be endemic to the tropical rainforests of Central and West Africa. However, the current monkeypox outbreak in nonendemic countries is most likely due to failure to curb the disease dissemination in endemic African regions despite decades of constant outbreaks. The clinical manifestations are typified by a prodromal phase (fever, myalgia, malaise, and lymphadenopathy) followed by maculopapular or vesicular, or pustular cutaneous eruptions that eventually form encrustations and peel off. Children and the elderly, pregnant females, and individuals living with comorbidities (diabetes, HIV/AIDS, and lymphoproliferative ailments) are at a high risk of severe disease. Monkeypox is a self-limiting disorder, but its complications and pandemic potential signify its immense public health relevance. The recent ongoing monkeypox outbreak in nonendemic nations areas was identified with increased propensity in men who have sex with men (MSMs) with no travel history to endemic regions, emphasizing the changing trends in disease transmission. This review article provides an updated overview of the monkeypox disease taxonomy, pathogenesis, transmission, epidemiology, clinical and oral features, diagnostic aids, differential diagnosis, preventive aspects, and treatment protocol.

Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C.

OBJECTIVE: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. METHODS: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. RESULTS: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. CONCLUSIONS: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. GOV IDENTIFIER: NCT03759639.

The COVID-19 pandemic in older people

Summary The incidence, severity, and mortality of COVID-19 infection appear to impact the elderly more negatively, especially in those who are frail and have multiple comorbidities. This chapter reviews the epidemiology of the COVID-19 pandemic with a focus on the older age group. The transmission of the virus to humans likely occurs through the consumption of an infected animal as a source of food, followed by human-to-human transmission through close contact. The epidemiology of COVID-19 incidence, severity of illness, and mortality appear to have unfavourable outcomes for older people. Managing older people with COVID-19 infection includes symptomatic therapy that focuses on the direct relief of the typical symptoms of COVID-19, drug therapy that focuses on agents directly treating the viral infection load, and general supportive care, which focuses on the relief of atypical symptoms in the acute setting. Ethical issue is the participation of older people in clinical trials.;Objective While endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19. Methods Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA. Results Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation. Conclusion These data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.