D-lactic acidosis is associated with fermentative disturbances and is often marked by elevated levels of D-lactic acid in the blood, ruminal fluid, and synovial fluid in cattle. D-lactic acidosis is linked to various inflammatory manifestations, and although the causative factors have been extensively explored, the exact pathogenesis of the associated inflammation remains elusive. Notably, less attention has been given to D-lactate, a stereoisomer found in the plasma of affected animals, which may lead to D-lactic acidosis.
View Article and Find Full Text PDFDihydroorotate dehydrogenases (DHODs) catalyze the transfer of electrons between dihydroorotate and specific oxidant substrates. Class 1B DHODs (DHODBs) use NAD as the oxidant substrate and have a heterodimeric structure that incorporates two active sites, each with a flavin cofactor. One FeS center lies roughly equidistant between the flavin isoalloxazine rings.
View Article and Find Full Text PDFBackground & Aims: Incidence of obesity and Crohn's disease (CD) is increasing globally. Therefore, understanding any associations between adiposity and disease phenotype is crucial. We aimed explore the relationship between nutritional status measured by body mass index (BMI) and phenotypes of CD using a large national recallable data set.
View Article and Find Full Text PDFBackground: Inflammatory Bowel Disease (IBD) is a long-term condition affecting the digestive tract and is an umbrella term for two main conditions: ulcerative colitis (UC) and Crohn's Disease (CD), which can cause diarrhoea, anaemia, weight loss, rectal bleeding and abdominal pain. Approximately 500,000 people live with IBD in the UK, with half being diagnosed before the age of 35 years (Ferguson, Mahsud-Dornan, and Patterson 2008). IBD increases the risk of pregnancy complications, with symptoms being unpredictable during pregnancy.
View Article and Find Full Text PDFBioinform Biol Insights
September 2024
The advent of biobanks with vast quantities of medical imaging and paired genetic measurements creates huge opportunities for a new generation of genotype-phenotype association studies. However, disentangling biological signals from the many sources of bias and artifacts remains difficult. Using diverse medical images and time-series (ie, magnetic resonance imagings [MRIs], electrocardiograms [ECGs], and dual-energy X-ray absorptiometries [DXAs]), we show how registration, both spatial and temporal, guided by domain knowledge or learned , helps uncover biological information.
View Article and Find Full Text PDFBackground: Evidence is needed to understand factors that influence child development and caregiving experiences, especially in marginalized contexts, to inform the development and implementation of early childhood development (ECD) interventions. This study explores caregiving practices for young children in an urban informal settlement with Kenyans and embedded refugees, and identifies factors shaping these caregiving experiences, to inform the design and development of potentially appropriate ECD interventions.
Methods: A qualitative formative study, which included 14 focus group discussions (n = 125 participants), and 13 key informant interviews was conducted between August and October 2018.
Thioredoxin/glutathione reductase from Schistosoma mansoni (SmTGR) is a multifunctional enzyme that catalyzes the reduction of glutathione (GSSG) and thioredoxin, as well as the deglutathionylation of peptide and non-peptide substrates. SmTGR structurally resembles known glutathione reductases (GR) and thioredoxin reductases (TrxR) but with an appended N-terminal domain that has a typical glutaredoxin (Grx) fold. Despite structural homology with known GRs, the site of GSSG reduction has frequently been reported as the Grx domain, based primarily on aerobic, steady-state kinetic measurements and x-ray crystallography.
View Article and Find Full Text PDFFront Cell Infect Microbiol
September 2024
J Womens Health (Larchmt)
September 2024
To characterize the sociological risk factors for firearm intimate partner violence (IPV) among women in Texas, with a focus on lethal predictors to aid in screening and intervention guidelines. A retrospective medical and forensic chart review was conducted and supplemented by news sources, public police reports, and court records on firearm cases in Houston, TX, from 2018 to 2020. IPV was defined as a cis-gendered female victim of firearm violence from a current or ex-intimate partner.
View Article and Find Full Text PDFBackground & Aims: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals.
View Article and Find Full Text PDFDevelopment of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription.
View Article and Find Full Text PDFInflammasomes are multiprotein complexes that trigger processes through caspase-1 activation, leading to the maturation of proinflammatory cytokines, such as IL-1β and IL-18. The gene encoding the inflammasome stimulatory protein NLRP3 is conserved in canines. Caspase-1/4 homologues have been identified in multiple carnivores, including canines, and caspase-1 activity has been shown in humans.
View Article and Find Full Text PDFWe examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration.
View Article and Find Full Text PDFThis article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations.
View Article and Find Full Text PDFIn 2022, a global mpox outbreak occurred, primarily affecting gay and bisexual men who have sex with men (GBMSM). To screen for mpox's reemergence and investigate potentially unsuspected cases among non-GBMSM, prospective surveillance of patients aged ≥3 months with an mpox-compatible rash (vesicular, pustular, ulcerated, or crusted) was conducted at 13 U.S.
View Article and Find Full Text PDFContinued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the () gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models.
View Article and Find Full Text PDFObjective: The introduction of peer support in mental health teams creates opportunities and challenges for both peer and non-peer staff. However, the majority of research on mental health workers' (MHWs) experiences with peer support comes from high-income countries. Using Peer Support In Developing Empowering Mental Health Services (UPSIDES) is an international multicentre study, which aims at scaling up peer support for people with severe mental illness in Europe, Asia and Africa.
View Article and Find Full Text PDFWith the movement towards recovery-oriented mental health (MH) services, individuals with MH lived-experience are increasingly employed as peer providers (peers). Peers are unique in that they bring knowledge from experience and eye-level connection to service users that enhance the quality of services and humanize MH systems' culture. In Israel, hundreds of peers are employed in various roles and settings across the MH system.
View Article and Find Full Text PDFThe physiological role of dihydroorotate dehydrogenase (DHOD) enzymes is to catalyze the oxidation of dihydroorotate to orotate in pyrimidine biosynthesis. DHOD enzymes are structurally diverse existing as both soluble and membrane-associated forms. The Family 1 enzymes are soluble and act either as conventional single subunit flavin-dependent dehydrogenases known as Class 1A (DHODA) or as unusual heterodimeric enzymes known as Class 1B (DHODB).
View Article and Find Full Text PDFTamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like conditions in horses, revealing specific impacts on the innate immune system.
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