Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males.

Objectives: To examine the effect of the NAD precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.

Methods: In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.

Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).

Structural and functional sex differences in medial temporal lobe subregions at midlife.

Background: Research has increasingly recognized sex differences in aging and Alzheimer's Disease (AD) susceptibility. However, sex effects on the medial temporal lobe (MTL), a crucial region affected by aging and AD, remain poorly understood when it comes to the intricacies of morphology and functional connectivity. This study aimed to systematically analyze structural and functional connectivity among MTL subregions, which are known to exhibit documented morphological sex differences, during midlife, occurring before the putative pivotal age of cerebral decline.

Association between large neutral amino acids and white matter hyperintensities in middle-aged adults at varying metabolic risk.

This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, these relationships often reverse later in life. Our study hypothesized an earlier reversal of these benefits in middle-aged adults with MetS, potentially signaling premature brain aging.

Defining non-inferiority margins in randomised controlled surgical trials: a protocol for a systematic review.

Background: The reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial.