Effect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.

Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination.

Identifying barriers and potential solutions to improve equitable access to community eye services: an exploratory sequential mixed methods study protocol.

Introduction: Access to care varies by sociodemographic group, with some groups facing higher barriers to care than others. This study will use novel methods to explore barriers and potential solutions as perceived by members of the population groups who are least able to access care. We aim to use rapid yet robust mixed methods that allow us to identify generalisable findings within each programme and testable service modifications to improve equitable access to care; delivering non-tokenistic findings within a matter of weeks.

Evaluating Metabolic Profiling of Human Milk Using Biocrates MxP QUANT 500 Assay.

Metabolic profiling of human milk (HM) is indispensable for elucidating mother-milk-infant relationships. We evaluated the Biocrates MxP Quant 500 assay for HM-targeted metabolomics (106 small molecules, 524 lipids) and analyzed in a feasibility test HM from apparently healthy Brazilian mothers (A: 2-8, B: 28-50, C: 88-119 days postpartum, n = 25). Of the 630 possible signatures detectable with this assay, 506 were above the limits of detection in an HM-pool (10 µL) used for assay evaluation, 12 of them above the upper limit of quantitation.

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

Chronic muscle fatigue is a condition characterized by debilitating muscle weakness and pain. Based on our recent finding to study the potential effect of mTOR on ATG13 inactivation in chronic muscle fatigue, we report that biweekly oral administration with MHY1485, a potent inducer of mTOR, develops chronic illness in mice resulting in severe muscle weakness. As a mechanism, we observed that MHY1485 feeding impaired ATG13-dependent autophagy, caused the infiltration of inflammatory M1 macrophages (Mφ), upregulated IL6 and RANTES by STAT3 activation, and augmented demyelination in muscle-serving nerve fibers.

Effects of the pan-caspase inhibitor Q-VD-OPh on human neutrophil lifespan and function.

Human neutrophils are abundant, short-lived leukocytes that turn over at a rate of approximately 1011 cells/day via a constitutive apoptosis program. Certain growth factors, inflammatory mediators and infectious agents can delay apoptosis or induce neutrophils to die by other mechanisms. Nonetheless, a large body of data demonstrates that apoptosis of untreated neutrophils typically ensues within 24 hours of cell isolation and in vitro culture.