Defining and reporting adverse events of special interest in comparative maternal vaccine studies: a systematic review.

Introduction: The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research.

Critical role for the lung endothelial nonmuscle myosin light-chain kinase isoform in the severity of inflammatory murine lung injury.

Global knockout of the nonmuscle isoform of myosin light-chain kinase (nmMLCK), a primary cellular regulator of cytoskeletal machinery, is strongly protective in preclinical murine models of inflammatory lung injury. The current study was designed to assess the specific contribution of endothelial cell (EC) nmMLCK to the severity of murine inflammatory lung injury produced by lipopolysaccharide (LPS) and mechanical ventilation ventilator-induced lung injury or ventilation (VILI). Responses to combined LPS/VILI exposure were assessed in: (i) wild-type (WT) C57BL/6J mice; (ii) transgenic mice with global deletion of nmMLCK ( ); (iii) transgenic nm mice with overexpression of nmMLCK restricted to the endothelium ( ).

eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling.

Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects.

Indirect effects of COVID-19 on maternal, neonatal, child, sexual and reproductive health services in Kampala, Uganda.

Background: COVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown that restricted individuals' movements in Uganda limited access to services.

Methods: An observational study, using routinely collected data from Electronic Medical Records, was carried out, in Kawempe district, Kampala.

Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody.

Rationale: The severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target.

Methods: Wild-type C57BL/6J or endothelial cell (EC)-c knockout mice (targeted EC deletion) were exposed to either a lipopolysaccharide (LPS)-induced ("one-hit") or a combined LPS/ventilator ("two-hit")-induced acute inflammatory lung injury model.

American Chemical Society - 240th national meeting - chemistry for preventing and combating disease: part 1.

The 240th National Meeting of the American Chemical Society, held in Boston, included topics covering new therapeutic research. This conference report highlights selected presentations on negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5) for the treatment of Parkinson's disease, BACE1 inhibitors and γ-secretase inhibitors for the prevention or treatment of Alzheimer's disease, opioid modulators for the treatment of reward disorders, SGLT2 inhibitors for the treatment of diabetes, backup compounds to the DPP-4 inhibitor sitagliptin (Januvia) for type 2 diabetes, and MCH R1 inhibitors for the treatment of obesity. Investigational drugs discussed include SCH-1359113 and SCH-1682496 (both Merck & Co), NGP-555 (NeuroGenetic Pharmaceuticals), ALKS-33 (Alkermes), dapagliflozin (Bristol-Myers Squibb/AstraZeneca) and GSK-882380 (GlaxoSmithKline).

The parallel synthesis of a disaccharide library using a solid phase, peptide-templated strategy.

A novel strategy for the synthesis of oligosaccharides, involving the use of a solid phase peptide template, has been successfully applied to the construction of a twelve member disaccharide library.