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Background: Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer., Methods: Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m 2 ) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m 2 ). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling., Results: OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day -1 , p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160 Thr642 (p = 0.046) post-HIIT., Conclusions: A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass)., (© 2023. The Author(s).)

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., Results: Resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD + -specific pathways (e.g., de novo NAD + biosynthetic processes) and genes (e.g., NADSYN1 ) were uniquely regulated by NA., Conclusions: NA might be an effective strategy for improving ageing muscle mitochondrial health., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter on behalf of Shangai Jiao Tong University and Guangzhou Sport University.)

We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. (Funded by the National Institute for Health and Care Research and others.)., (Copyright © 2024 Massachusetts Medical Society.)