The goal of this study was to evaluate characteristics associated with Pre-exposure Prophylaxis for HIV infection (PrEP) non-adherence or discontinuation in Brazil and assess the association between these outcomes and HIV seroconversion. We used linked national dispensing and pathology data to identify people aged 14+ years initiating PrEP in 2018. We estimated non-adherence using the proportion of days covered (PDC), defining non-adherence as PDC < 60%.
View Article and Find Full Text PDFWe developed a novel adeno-associated virus 5 gene therapy (AAV5-GLA) expressing human alpha-galactosidase A (GLA) under the control of a novel, small and strong, liver-restricted promoter. We assessed the preclinical potential of AAV5-GLA for treating Fabry disease, an X-linked hereditary metabolic disorder resulting from mutations in the gene encoding GLA that lead to accumulation of the substrates globotriaosylceramide and globotriaosylsphingosine, causing heart, kidney, and central nervous system dysfunction. Effects of intravenously administered AAV5-GLA were evaluated in (1) GLA-knockout mice aged 7-8 weeks (early in disease) and 20 weeks (nociception phenotype manifestation) and (2) cynomolgus macaques during an 8-week period.
View Article and Find Full Text PDFThe first outbreaks of coronavirus CoV, SARS-CoV and MERS-CoV have occurred in China and Saudi Arabia over the past decade, respectively. From the end of 2019, a great battle began by the world scientific community against SARS-CoV-2, the virus that caused COVID-19, a pathology that generated devastating consequences on all existing continents. Several mutations have already been detected in the structure of the virus, which have been responsible for the generation of many types of variants since the detection of the first COVID-19 virus identified in China.
View Article and Find Full Text PDFAn increase in global infertility has coincided with the accumulation of microplastics (MPs) in the environment. This trend is particularly troubling because only 10% of male infertility cases can be attributed to identifiable causes, leaving a knowledge gap in our understanding of their underlying factors. To bridge this, it is important to explore the connection between the accumulation of MPs and the observed decline in male fertility.
View Article and Find Full Text PDFClin Transplant
October 2024
Background And Aim: Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC.
View Article and Find Full Text PDFGiven the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown.
View Article and Find Full Text PDFThe human Golgi α-mannosidase, hGMII, removes two mannose residues from GlcNAc-ManGlcNAc to produce GlcNAcManGlcNAc, the precursor of all complex -glycans including tumour-associated ones. The natural product GMII inhibitor, swainsonine, blocks processing of cancer-associated -glycans, but also inhibits the four other human α-mannosidases, rendering it unsuitable for clinical use. Our previous structure-guided screening of iminosugar pyrrolidine and piperidine fragments identified two micromolar hGMII inhibitors occupying the enzyme active pockets in adjacent, partially overlapping sites.
View Article and Find Full Text PDFThis study aimed to evaluate the toxicity of essential oil (PHEO) against 11 Brazilian populations of (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth () of the insect populations were investigated. PHEO toxicity was determined through concentration-mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.
View Article and Find Full Text PDFNeonatal stress affects psychological and physiological development and may be associated with affective disorders. The aim was to examine the effects of double neonatal stress (DNS) - a combination of limited bedding and nesting (LBN) and repeated maternal separation (MS) - on the oestrous cycle and sexual behaviour of adult female rats. LBN was achieved by removing part of the wood shavings from the boxes.
View Article and Find Full Text PDFCalcium phosphate (CaP) scaffolds doping with therapeutic ions are one of the focuses of recent bone tissue engineering research. Among the therapeutic ions, strontium stands out for its role in bone remodeling. This work reports a simple method to produce Sr-doped 3D-printed CaP scaffolds, using Sr-doping to induce partial phase transformation from β-tricalcium phosphate (β-TCP) to hydroxyapatite (HA), resulting in a doped biphasic calcium phosphate (BCP) scaffold.
View Article and Find Full Text PDFObjective: to analyze the moral sensitivity of Brazilian emergency care nurses according to their personal and work characteristics.
Method: this is a quantitative, descriptive, cross-sectional study with a convenience sample. A total of 422 nurses from emergency care services in the five regions of Brazil took part.
Regardless of the containment of the SARS-CoV-2 pandemic, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provides anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms.
View Article and Find Full Text PDFClin Res Hepatol Gastroenterol
October 2024
Objective: Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40 % of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation.
View Article and Find Full Text PDFPurpose: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard.
Material And Methods: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping.
Autoimmune hepatitis is a rare chronic liver disease, associated with a high level of morbidity and high mortality; approximately 40% of patients with severe untreated disease die within 6 months of diagnosis. It should be treated to achieve complete biochemical and histologic resolution of the disease using corticosteroids and immunosuppression to prevent further progression to cirrhosis. The use of invasive liver biopsy is recommended for the staging and assessment of inflammation and fibrosis for treatment decision-making in the face of an unsatisfactory response or clinical remission, including being a determinant for withdrawal of immunosuppression.
View Article and Find Full Text PDFBackground: Chronic excessive use of alcohol is an important risk factor for several health and social conditions.
Methods: A cross-sectional survey, in a sample representative of the Brazilian population,was conducted to evaluate the frequency of consumption of alcoholic beverages and behaviors concerning liver diseases. Participants were prospectively interviewed using a questionnaire regarding alcohol consumption and actions toward liver health.
Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH.
View Article and Find Full Text PDFPresently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection.
View Article and Find Full Text PDFEur J Gastroenterol Hepatol
May 2024
Background: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA.
Methods: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA.
Understanding the mechanical properties and porosity of reproductive tissues is vital for regenerative medicine and tissue engineering. This study investigated the changes in Young's modulus (YM), storage modulus (E'), loss modulus (E"), and porosity of native and decellularized bovine reproductive tissues during the estrous cycle. Testis tunica albuginea had significantly higher YM, E', and E" than the inner testis, indicating greater stiffness and viscoelasticity.
View Article and Find Full Text PDFThe objective of the current study was to evaluate the effects of tannin and monensin supplementation in feedlot diets and breed (Holstein vs. Angus × Holstein) on growth performance, energetic efficiency, and carcass characteristics. Eighty purebred Holstein calves (HOL; initial body weight (BW) = 130 ± 5 kg) and 80 Angus × Holstein calves (AXH; initial BW = 129 ± 6 kg) were blocked by initial BW and randomly assigned to 40 pens.
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