Epithelial neutrophil localization and tight junction Claudin-2 expression are innovative outcome predictors in inflammatory bowel disease.

Background: Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted.

CRISPR screen for rAAV production implicates genes associated with infection.

Recombinant adeno-associated virus (rAAV) vectors are an effective and well-established tool in the growing gene therapy field, with five FDA-approved AAV-mediated gene therapies already on the market and numerous more in clinical trials. However, manufacturing rAAV vectors is an expensive, timely, and labor-intensive process that limits the commercial use of AAV-mediated gene therapies. To address this limitation, we screened producer cells for genes that could be targeted to increase rAAV yield.

Perspectives of People with Stroke, Caregivers and Healthcare Professionals on an Adaptive mHealth Intervention for Physical Activity in the Prevention of Secondary Stroke: A Qualitative Study.

Introduction: Engaging in regular physical activity (PA) is associated with lower mortality following stroke, and PA reduces the chance of recurrent stroke. Despite recent guidelines to optimise PA following stroke, people with stroke are known to be less active than their age-matched counterparts. Given the heterogenous nature of stroke, adaptive PA interventions are recommended for people with stroke.

Role of Epithelial-to-Mesenchymal Transition of Retinal Pigment Epithelial Cells in Glaucoma Cupping.

Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of retinal pigment epithelium (RPE) adjacent to the ONH. Under pro-fibrotic conditions, epithelial cells throughout the body can differentiate into fibroblast-like cells through epithelial-to-mesenchymal transition (EMT) and contribute to ECM fibrosis.

Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins.

Background: Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development and plasticity. Most MHCI are transmembrane proteins. The extracellular domain of MHCI interacts with immunoreceptors, peptides, and co-receptors to mediate immune signaling.

Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with type 2 diabetes mellitus.

Sergliflozin, the active entity of sergliflozin etabonate, is a selective inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The pharmacokinetics and pharmacodynamics of sergliflozin were evaluated following single oral dose administration of sergliflozin etabonate (5-500 mg) in healthy volunteers (n = 22) and patients with type 2 diabetes mellitus (n = 8). The prodrug was rapidly and extensively converted to sergliflozin; the latter displayed linear kinetics, reached maximum plasma concentrations at approximately 30 to 45 minutes postdose (t(max)), and had a plasma elimination half-life (t(1/2)) of approximately 0.

L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model.

l-2-hydroxyglutaric aciduria (l-2-HGA) is a neurometabolic disorder that produces a variety of clinical neurological deficits, including psychomotor retardation, seizures and ataxia. The biochemical hallmark of l-2-HGA is the accumulation of l-2-hydroxyglutaric acid (l-2-HG) in cerebrospinal fluid, plasma and urine. Mutations within the gene L2HGDH (Entrez Gene ID 79944) on chromosome 14q22 encoding L-2-hydroxyglutaric acid dehydrogenase have recently been shown to cause l-2-HGA in humans.

Monitoring enzyme replacement therapy in Fabry disease--role of urine globotriaosylceramide.

Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme. Enzyme replacement therapy (ERT) offers a specific treatment for patients with Fabry disease, though monitoring of treatment is hampered by a lack of surrogate markers of response. In this study, the efficacy of long-term ERT in six Fabry hemizygotes and two symptomatic heterozygotes has been evaluated.

Strategic planning in medical education: enhancing the learning environment for students in clinical settings.

Background: The 1999 Cambridge Conference was held in Northern Queensland, Australia, on the theme of clinical teaching and learning. It provided an opportunity for groups of academic medical educators to consider some of the challenges posed by recent changes to health care delivery and medical education across a number of countries.

Purpose: This paper describes the issues raised by the practical challenges posed by the current environment and how they might be addressed in ways that could promote more effective learning in clinical settings.

Syntheses of 1,2-diamino and 1,2-aminoalcohol derivatives in the piperidine and pyrrolidine series as anti-amnesic agents.

Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine has been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research is a continuation of our efforts in the area of 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) (cf.

Syntheses of benzoquinolizidine and benzoindolizidine derivatives as anti-amnesic agents.

Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine have been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research was undertaken to produce an acetylcholinesterase inhibitor by employing 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) as templates.

Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at a hydrophobic centre.

Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid, we synthesized a series of analogues with n-alkyl side chains of increasing length and correlated their potential to induce neural tube defects and to inhibit proliferation and induce differentiation in cells of neural origin, the latter being crucial to the orderly structuring of the embryo. All analogues significantly increased the incidence of neural tube defects in the embryos of dams exposed to a single dose of 1.

Valproic acid suppresses G1 phase-dependent sialylation of a 65kDa glycoprotein in the C6 glioma cell cycle.

The influence of valproate on in vitro glycosylation events in C6 glioma has been investigated, as this major human teratogen restricts proliferation in the mid-G1 phase of the cycle and alters the prevalence and/or glycosylation state of cell surface glycoproteins with the potential to mediate cell-cell and cell matrix interactions critical to development. C6 glioma cultured continuously in the presence of 1 mM valproate exhibited a significant depression of exponential growth but attained confluency one day later, when the majority of cells entered the G1 phase of the cycle. Glycoprotein sialyltransferase, which exhibited a four-fold increase during exponential growth and a small decrease at confluency, was markedly attenuated in valproate-exposed cells in a manner which was indirect.