Boonehay6304

Information regarding predictors of a worse COVID-19 prognosis in the South American population is scarce. We aimed to determine whether the blockade of the renin-angiotensin system is associated with a worse clinical course of COVID-19, and to evaluate what clinical variables are associated with COVID severity in our population. We included adult subjects with rtPCR-confirmed COVID-19. The use of renin system inhibitors was defined according to its registration in the electronic medical record or the hospital pharmacy registry during the previous three months. Our endpoint was a composite of death or mechanical ventilation requirement. Patients were followed up until discharge or death. A multiple logistic regression model was used to determine the predictors of the composite endpoint. In all, we included 4930 COVID+ patients, the median age was 52 years, and 48.1% were male. The endpoint occurred in 488 patients (9.9%). In adjusted analysis, neither angiotensin converting enzyme inhibitors nor angiotensin receptor blockers were associated with the outcome. Independent predictors of mortality and/or mechanical ventilation requirement were age, male sex, a history of diabetes and/or chronic kidney disease, smoking and dementia. To conclude, renin system inhibitors seem to be unrelated to COVID-19 severity, whereas prognosis is independently associated with age, male sex and comorbidities.Visceral leishmaniasis is a neglected zoonotic disease that affects animals and humans in different tropical and subtropical regions and even beyond, with variable prevalence among infected hosts. To date, there have been no systematic reviews on human visceral leishmaniasis prevalence in Latin America. We therefore performed a systematic literature review with meta-analysis, using six databases to assess prevalence of visceral leishmaniasis in human patients in Latin American countries. Observational studies were included but analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). In all, 10,435 articles were retrieved for the time frame (1950-2019). After initial screening, 120 articles were selected for full-text assessment, 97 being finally included for qualitative and quantitative analyses. Overall, VL pooled prevalence was estimated at 38.8% (95% CI 33.8-43.8%), derived from 97 studies, including 44,986 individuals. Many aspects of the transmission dynamics of Leishmania and the exact burden of this parasitosis on public health remain largely unknown. Although the elimination of zoonotic VL in the Americas appears an unrealistic goal, additional efforts need to be put in place to achieve better diagnosis, treatment, and prevention of VL.Sporotrichosis is a fungal infection occurring worldwide, especially in tropical and sub-tropical areas. We present a brief review of clinical and epidemiological aspects of sporotrichosis, as well as its treatment. Sporotrichosis is rarely reported in Europe and the European Centre of Disease Control does not track its infection rate. To fill this gap, we report a survey of clinical cases described over the past forty years in Europe and in Italy.In recent years, and now especially with the arrival of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been increased interest in understanding the role of bats in the dynamics of transmission and origin of this pandemic agent. To date, no systematic reviews have been published on this topic. This systematic review aimed to summarize and highlight the frequency of bat infections reported in currently available observational studies for coronavirus. The purpose of this study was also to examine the differences between the pool prevalence by technique and country. We performed a systematic literature review with meta-analysis, using three databases to assess coronavirus (CoV) infection in bats and its diagnosis by serological and molecular tests. We carried out random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95% CI). In all, 824 articles were retrieved (1960-2021). After screening by abstract/title, 43 articles were selected for full-text assessment. Of these, 33 were finally included for qualitative and quantitative analyses. From the total of studies, the pool prevalence by RT-PCR (n=14,295 bats) for CoV was 9.8% (95% CI 8.7-10.9%); Italy reported the highest pooled prevalence (44.9%, 95% CI 31.6-58.1%), followed by the Philippines (29.6%). Regarding the ELISA, the pool prevalence for coronavirus from 15 studies, including 359 bats, was 30.2% (95% CI 14.7-45.6%). The results for coronaviruses with the MIF were significantly lower, 2.6% (95% CI 1.5-3.7%). A considerable proportion of infected bats tested positive, particularly by molecular tests. This essential condition highlights the relevance of bats and the need for future studies to detail their role as potential reservoirs of SARS-CoV-2. In this meta-analysis, bats were positive in almost 10% by RT-PCR, suggesting their relevance and the need to understand their potential participation in maintaining wild zoonotic transmission.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.Multiple myeloma (MM), a terminally differentiated B cell malignancy, remains difficult to cure. Understanding the molecular mechanisms underlying the progression of MM may identify therapeutic targets and lead to a fundamental shift in treatment of the disease. Deubiquitination, like ubiquitination, is a highly regulated process, implicated in almost every cellular process. Multiple deubiquitinating enzymes (DUBs) have been identified, but their regulation is poorly defined. Here, we determined that TRIP13 increases cellular deubiquitination. Overexpression of TRIP13 in mice and cultured cells resulted in excess cellular deubiquitination by enhancing the association of the DUB USP7 with its substrates. We show that TRIP13 is an oncogenic protein because it accelerates B cell tumor development in transgenic mice. TRIP13-induced resistance to proteasome inhibition can be overcome by a USP7 inhibitor in vitro and in vivo. These findings suggest that TRIP13 expression plays a critical role in B cell lymphoma and MM by regulating deubiquitination of critical oncogenic (NEK2) and tumor suppressor (PTEN, p53) proteins. High TRIP13 identifies a high-risk patient group amenable to adjuvant anti-USP7 therapy.The emergence of the novel SARS coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in an unprecedented pandemic that has been accompanied by a global health crisis. Although the lungs are the main organs involved in COVID-19, systemic disease with a wide range of clinical manifestations also develops in patients infected with SARS-CoV-2. One of the major systems affected by this virus is the cardiovascular system. The presence of preexisting cardiovascular disease increases mortality in patients with COVID-19, and cardiovascular injuries, including myocarditis, cardiac rhythm abnormalities, endothelial cell injury, thrombotic events, and myocardial interstitial fibrosis, are observed in some patients with COVID-19. The underlying pathophysiology of COVID-19-associated cardiovascular complications is not fully understood, although direct viral infection of myocardium and cytokine storm have been suggested as possible mechanisms of myocarditis. In this Review, we summarize available data on SARS-CoV-2-related cardiac damage and discuss potential mechanisms of cardiovascular implications of this rapidly spreading virus.The main mechanisms underlying sexually dimorphic outcomes in neonatal lung injury are unknown. We tested the hypothesis that hormone- or sex chromosome-mediated mechanisms interact with hyperoxia exposure to impact injury and repair in the neonatal lung. To distinguish sex differences caused by gonadal hormones versus sex chromosome complement (XX versus XY), we used the Four Core Genotypes (FCG) mice and exposed them to hyperoxia (95% FiO2, P1-P4 saccular stage) or room air. This model generates XX and XY mice that each have either testes (with Sry, XXM, or XYM) or ovaries (without Sry, XXF, or XYF). Lung alveolarization and vascular development were more severely impacted in XYM and XYF compared with XXF and XXM mice. Cell cycle-related pathways were enriched in the gonadal or chromosomal females, while muscle-related pathways were enriched in the gonadal males, and immune-response-related pathways were enriched in chromosomal males. Female gene signatures showed a negative correlation with human patients who developed bronchopulmonary dysplasia (BPD) or needed oxygen therapy at 28 days. These results demonstrate that chromosomal sex - and not gonadal sex - impacted the response to neonatal hyperoxia exposure. The female sex chromosomal complement was protective and could mediate sex-specific differences in the neonatal lung injury.Exposure to maternal obesity may promote metabolic dysfunction in offspring. We used infant mesenchymal stem cells (MSCs) to experimentally examine cellular mechanisms of intergenerational health transmission. (E/Z)-BCI research buy Our earlier reports show MSCs collected from infants of mothers with obesity had a dichotomous distribution in metabolic efficiency; they were either efficient (Ef-Ob) or inefficient (In-Ob) with respect to fatty acid oxidation (FAO). Here, we sought to determine if this was due to a primary defect in FAO. Accordingly, we measured FAO in myogenic differentiating MSCs under 3 conditions (a) myogenesis alone, (b) excess fatty acid exposure, and (c) excess fatty acid exposure plus a chemical uncoupler to increase metabolic rate. Compared with normal weight and Ef-Ob MSCs, In-Ob displayed lower FAO in myogenesis alone and after fatty acid plus uncoupler, indicating In-Ob were less metabolically flexible after increasing lipid availability and metabolic rate, demonstrating a primary deficit in FAO. MSC FAO was negatively associated with fasting maternal glucose and insulin and positively associated with fasting HDL-cholesterol.