Food fortification (i.e., industrial fortification and biofortification) increases the micronutrient content of foods to improve population nutrition.
View Article and Find Full Text PDFChikungunya virus (CHIKV) is an arthritogenic alphavirus that has re-emerged to cause large outbreaks of human infections worldwide. There are currently no approved antivirals for treatment of CHIKV infection. Recently, we reported that the ribonucleoside analog 4'-fluorouridine (4'-FlU) is a highly potent inhibitor of CHIKV replication, and targets the viral nsP4 RNA dependent RNA polymerase.
View Article and Find Full Text PDFImportance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.
Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.
Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens. Here, we address questions of how LECs achieve durable antigen archiving and whether LECs with high levels of antigen express unique transcriptional programs. We used single cell sequencing in dissociated LN tissue and spatial transcriptomics to quantify antigen levels in LEC subsets and dendritic cell populations at multiple time points after immunization and determined that ceiling and floor LECs archive antigen for the longest duration.
View Article and Find Full Text PDFThe alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies.
View Article and Find Full Text PDFAs outbreaks of chikungunya virus (CHIKV), a mosquito-borne alphavirus, continue to present public health challenges, additional research is needed to generate protective and safe vaccines and effective therapeutics. Prior research has established a role for antibodies in mediating protection against CHIKV infection, and the early appearance of CHIKV-specific IgG or IgG neutralizing antibodies protects against progression to chronic CHIKV disease in humans. However, the importance of epitope specificity for these protective antibodies and how skewed responses contribute to development of acute and chronic CHIKV-associated joint disease remains poorly understood.
View Article and Find Full Text PDFDuring viral infection, phagocytic cells participate in numerous immunological processes. A common approach to elucidate the specific contributions of phagocytic cells is through direct comparison of viral pathogenesis of phagocyte-depleted and phagocyte-intact animals. Clodronate liposomes are a versatile and simple means of depleting phagocytes in any animal model.
View Article and Find Full Text PDF2-(Methylthio)--(4-(naphthalen-2-yl)thiazol-2-yl)nicotinamide was identified as an inhibitor against Chikungunya virus (CHIKV) with good antiviral activity [EC = 0.6 μM; EC = 0.93 μM and viral titer reduction (VTR) of 6.
View Article and Find Full Text PDFRA-0003022 () was identified as a high-quality covalent chemical probe for nsP2 cysteine protease (nsP2pro). Isoxazole covalently captured the active site C478 and inactivated the enzyme with a / ratio of 6000 Ms. A negative control analog RA-0025453 () retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition.
View Article and Find Full Text PDFRoss River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8 T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8 T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8 T cells. After footpad injection, we detected fewer gp33-specific CD8 T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot.
View Article and Find Full Text PDFAim: Despite advancements in therapeutic options for Crohn's disease (CD), strictureplasty is a mainstay bowel-preserving technique for small bowel CD. We sought to audit international practice across three high-volume centres since the widespread use of biologic medication.
Methods: A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15-year period (2006-2021), in three high-volume centres in the United Kingdom and Italy.
Motivation: Conditional testing via the knockoff framework allows one to identify-among a large number of possible explanatory variables-those that carry unique information about an outcome of interest and also provides a false discovery rate guarantee on the selection. This approach is particularly well suited to the analysis of genome-wide association studies (GWAS), which have the goal of identifying genetic variants that influence traits of medical relevance.
Results: While conditional testing can be both more powerful and precise than traditional GWAS analysis methods, its vanilla implementation encounters a difficulty common to all multivariate analysis methods: it is challenging to distinguish among multiple, highly correlated regressors.
Given the psychological aspects of sports nutrition, understanding one's athletic identity (AI) may improve targeted nutrition education. Therefore, the purpose of this study was to examine nutrition habits and AI among uninjured youth athletes. Athletic Identity Measurement Scale (AIMS) and custom Sports Nutrition Assessment for Consultation (SNAC) scores collected prospectively at local sporting events were retrospectively assessed via Mann-Whitney, Kruskal-Wallis, logistic regression, and ANCOVA tests (95% CI).
View Article and Find Full Text PDFBackground: Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated.
View Article and Find Full Text PDFAnti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice.
View Article and Find Full Text PDFDespite increased scholarly attention being paid to minority stress and sexual satisfaction among sexual minorities, to our knowledge, no researchers have attempted to systematically synthesize this literature. To address this omission, we conducted a meta-analytic review of the association between sexual minority stress (i.e.
View Article and Find Full Text PDFSystematic detection of risky nutrition behaviors after sports surgery may better promote healing for return-to-sport. The purpose of this study was to assess nutritional behavior differences between patients following anterior cruciate ligament reconstruction (ACLR) and following other lower-extremity orthopedic surgeries. One pediatric sports medicine center was reviewed for a custom Sports Nutrition Assessment for Consultation, which investigates nutrition-related risk factors for youth athletes at their first post-operative visit.
View Article and Find Full Text PDFIn this primer, following best practice recommendations and drawing upon their own expertise in psychometrics, the authors provide a step-by-step guide for developing measures relevant to sexual- and gender-marginalized persons (SGMPs). To ensure that readers operate from a uniform understanding, definitions for central elements of psychometric testing (e.g.
View Article and Find Full Text PDFWe previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination.
View Article and Find Full Text PDFThis study investigated trends within a custom Sports Nutrition Assessment for Consultation (SNAC) survey designed to identify nutrition-related risk factors among post-operative lower-extremity youth athletes. Athletes aged 8-18 years who completed the SNAC at a sports medicine institution after lower-extremity surgery were reviewed for associations between SNAC questions and age/sex differences. Of 477 patients (15.
View Article and Find Full Text PDFWhen combined with healthcare pressures, the exponential growth of robotic-assisted surgery (RAS) has impacted UK-based training outcomes, including the learning curve to competency. Aim: To ascertain the current provision of RAS and investigate differences in access to minimal access surgical (MAS) facilities and training across the UK. A two-armed electronic survey was conducted.
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