Preferences for Delivery of HIV Prevention Services Among Healthcare Users in South Africa: A Discrete Choice Experiment.

Progress has been made to scale oral pre-exposure prophylaxis (PrEP) as part of combination HIV prevention, with the WHO recommending differentiated, simplified and demedicalized approaches. This study explored user preferences for components of a PrEP service delivery package, through a discrete choice experiment (DCE) among 307 people accessing primary healthcare services in South Africa between November 2022 and February 2023. Attributes included were: Source of information about HIV prevention and PrEP; Site for PrEP initiation and follow-up; Frequency of follow-up; PrEP pick-up point; HIV testing whilst using PrEP; Contact between appointments.

Potential Metabolite Biomarkers of Multiple Sclerosis from Multiple Biofluids.

Multiple sclerosis (MS) is a chronic and progressive neurological disorder without a cure, but early intervention can slow disease progression and improve the quality of life for MS patients. Obtaining an accurate diagnosis for MS is an arduous and error-prone task that requires a combination of a detailed medical history, a comprehensive neurological exam, clinical tests such as magnetic resonance imaging, and the exclusion of other possible diseases. A simple and definitive biofluid test for MS does not exist, but is highly desirable.

Interferons in the Treatment of Multiple Sclerosis: A Clinical Efficacy, Safety, and Tolerability Update.

Interferon beta (IFNβ) was the first disease-modifying therapy available to treat multiple sclerosis (MS), providing patients with a treatment that resulted in reduced relapse rates and delays in the onset of disability. Four IFNβ drugs are currently approved to treat relapsing forms of MS: subcutaneous (SC) IFNβ-1b, SC IFNβ-1a, intramuscular IFNβ-1a, and, most recently, SC peginterferon beta-1a. Peginterferon beta-1a has an extended half-life and requires less frequent administration than other available treatments (once every 2 weeks vs every other day, 3 times per week, or weekly).

The role of PERK and GCN2 in basal and hydrogen peroxide-regulated translation from the hepatitis C virus internal ribosome entry site.

We have previously shown that translation from the HCV IRES is up-regulated by patho/physiological doses of H(2)O(2) but is still sensitive to the inhibitory effect of phospho-eIF2α in hepatocytes. In this study using wild type and 'knockout' mouse embryonic fibroblasts (MEFs), we showed that two of the eIF2α kinases, PERK and GCN2, were not responsible for translational regulation under physiological and a higher apoptotic doses of H(2)O(2) (100 μM). However, a differential translational response was observed at a lower apoptotic dose of H(2)O(2) (50 μM) between Perk+/+ and Perk-/- MEFs but not that between Gcn2+/+ and Gcn2-/- MEFs, suggesting that PERK may play a role in translational up-regulation under oxidative stress.

Cap-dependent and hepatitis C virus internal ribosome entry site-mediated translation are modulated by phosphorylation of eIF2alpha under oxidative stress.

Chronic hepatitis C is often associated with oxidative stress. Hepatitis C virus (HCV) utilizes an internal ribosome entry site (IRES) element for translation, in contrast to cap-dependent translation of the majority of cellular proteins. To understand how virus translation is modulated under oxidative stress, HCV IRES-mediated translation was compared with cap-dependent translation using a bicistronic reporter construct and hydrogen peroxide (H2O2) as a stress inducer.

Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors.

The natural product willardiine (8) is an AMPA receptor agonist while 5-iodowillardiine (10) is a selective kainate receptor agonist. In an attempt to produce antagonists of kainate and AMPA receptors analogues of willardiine with substituents at the N3 position of the uracil ring were synthesized. The N3-4-carboxybenzyl substituted analogue (38c) was found to be equipotent at AMPA and GLUK5-containing kainate receptors in the neonatal rat spinal cord.