Chemical cyclization of tyrosine-containing peptides via in situ generated triazolinedione peptides.

Tyr-derived cyclic peptide natural products are formed by enzymatic manifolds that oxidatively cross-link embedded phenolic side chains of tyrosine (Tyr) and 4-hydroxyphenylglycine residues during their controlled production. Bioactive Tyr-derived cyclic peptides, such as the arylomycins and vancomycins, continue to motivate the development of enzymatic and chemical strategies for their de novo assembly and modification. However, chemical access to these structurally diverse natural cycles can be challenging and step intensive.

Herbal supplement Spirulina stimulates inflammatory cytokine production in patients with dermatomyositis .

Spirulina, an herbal supplement and popular ingredient in health foods, is a potent stimulant of the immune system. Spirulina use is temporally associated with the onset or exacerbation of Dermatomyositis (DM), an autoimmune connective tissue disease that frequently affects the skin and muscle. In this study, we investigated the effect of Spirulina on peripheral blood mononuclear cells (PBMCs) in DM and Healthy Controls (HCs), showing that Spirulina stimulates Interferon β (IFNβ), Tumor necrosis factor α (TNFα), and Interferon γ (IFNγ) production of DM PBMCs primarily via Toll-Like Receptor 4 (TLR4) activation using ELISA (enzyme linked immunosorbent assay) and flow cytometry.

Chemoselective, Oxidation-Induced Macrocyclization of Tyrosine-Containing Peptides.

Inspired by nature's wide range of oxidation-induced modifications to install cross-links and cycles at tyrosine (Tyr) and other phenol-containing residue side chains, we report a Tyr-selective strategy for the preparation of Tyr-linked cyclic peptides. This approach leverages N4-substituted 1,2,4-triazoline-3,5-diones (TADs) as azo electrophiles that react chemoselectively with the phenolic side chain of Tyr residues to form stable C-N1-linked cyclic peptides. In the developed method, a precursor 1,2,4-triazolidine-3,5-dione moiety, also known as urazole, is readily constructed at any free amine revealed on a solid-supported peptide.

Clinical, logistic, and geographic factors in ensuring adequate access to implant removals: A cross-sectional survey of public facilities and GIS modeling of geographic access in two districts of Senegal.

Introduction: Ensuring adequate access to contraceptive implant removal services requires an understanding of potential clinical, logistical, and geographic challenges.

Methods: We conducted a cross-sectional survey of 39 public health facilities in two districts of Senegal. To assess facility readiness, we reported the proportion of facilities meeting all minimum conditions for regular and difficult implant removals.

Effects of the COVID-19 pandemic on maternal and perinatal health service utilisation and outcomes in Mozambique: an interrupted time series analysis.

Objectives: To measure the effects of the COVID-19 pandemic on maternal and perinatal health services and outcomes in Mozambique.

Design: This is an observational study analysing routine service delivery data using interrupted time series analysis. We used 43 months of district-level panel data with April 2020 as the point of interruption, adjusting for seasonality and population growth to analyse service utilisation outcomes.

Autoimmune Skin Disease Exacerbations Following COVID-19 Vaccination.

Background: Vaccination against COVID-19 reduces the risk of severe COVID-19 disease and death. However, few studies have examined the safety of the COVID-19 vaccine in patients with autoimmune skin disease.

Objectives: We sought to determine the incidence of disease exacerbation in this population following COVID-19 vaccination as well as the associated factors.

Multidimensional Immune Profiling of Cutaneous Lupus Erythematosus In Vivo Stratified by Patient Response to Antimalarials.

Objective: The pathogenesis of cutaneous lupus erythematosus (CLE) is multifactorial, and CLE is difficult to treat due to the heterogeneity of inflammatory processes among patients. Antimalarials such as hydroxychloroquine (HCQ) and quinacrine (QC) have long been used as first-line systemic therapy; however, many patients do not respond to treatment with antimalarials and require systemic immunosuppressants that produce undesirable side effects. Given the complexity and the unpredictability of responses to antimalarial treatments in CLE patients, we sought to characterize the immunologic profile of patients with CLE stratified by subsequent treatment outcomes to identify potential biomarkers of inducible response.

Keeping essential reproductive, maternal and child health services available during COVID-19 in Kenya, Mozambique, Uganda and Zimbabwe: analysis of early-pandemic policy guidelines.

Background: The COVID-19 pandemic has disrupted the provision of essential reproductive, maternal, newborn, and child health (RMNCH) services in sub-Saharan Africa to varying degrees. Original models estimated as many as 1,157,000 additional child and 56,700 maternal deaths globally due to health service interruptions. To reduce potential impacts to populations related to RMNCH service delivery, national governments in Kenya, Mozambique, Uganda, and Zimbabwe swiftly issued policy guidelines related to essential RMNCH services during COVID-19.

Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications.

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes.

Assessment and management of the heightened risk for atherosclerotic cardiovascular events in patients with lupus erythematosus or dermatomyositis.

For patients with lupus erythematosus (LE) or dermatomyositis (DM), there is an urgent need to address a heightened risk of clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). Patients with LE or DM frequently exhibit high levels of conventional risk factors for ASCVD events, particularly dyslipoproteinemia and hypertension; an amplified burden of atherosclerotic plaques; and increased age- and sex-adjusted rates of ASCVD events compared with the general population. The rate of ASCVD events exceeds what would be expected from conventional risk factors, suggesting that disease-specific autoimmune processes exacerbate specific, known pathogenic steps in atherosclerosis.

Increased Colorectal Cancer Screening Sustained with Mailed Fecal Immunochemical Test Outreach.

Background & Aims: Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics.

Methods: A total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care.

Photosensitized Oxidative Dimerization at Tyrosine by a Water-Soluble 4-Amino-1,8-naphthalimide.

The oxidation of proteins generates reactive amino acid (AA) residue intermediates, leading to protein modification and cross-linking. Aerobic studies with peptides and photosensitizers allow for the controlled generation of reactive oxygen species (ROS) and reactive AA residue intermediates, providing mechanistic insights as to how natural protein modifications form. Such studies have inspired the development of abiotic methods for protein modification and crosslinking, including applications of biomedical importance.

Practical Implications of Policy Guidelines: A GIS Model of the Deployment of Community Health Volunteers in Madagascar.

Background: With increasing interest in strengthening community health programs nationally comes a need for operationalizing them in a realistic and achievable way. Limited information is available to help program managers establish appropriate parameters for their context. We examined aspects of program implementation related to deployment patterns of community health workers, called agents communautaires or ACs, in 2 districts of Madagascar.