The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal-cord injured athletes

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to β-alanine supplementation in spinal-cord injured athletes, sixteen male athletes with paraplegia were randomized (2:1 ratio) to receive β-alanine (n=11) or placebo (PL, n=5). They consumed 6.4 g‧d-1 of β-alanine or PL for 28 days. Muscle biopsies of the active deltoid and the inactive vastus lateralis (VL) were taken before and after supplementation. MCarn in the VL was also compared with the VL of a group of individuals without paraplegia (n=15). MCarn was quantified in whole muscle and in pools of individual fibers by High-performance Liquid Chromatography. MCarn was higher in chronically inactive VL vs. well-trained deltoid (32.0±12.0 vs. 20.5±6.1 mmol‧kg-1 DM; p=0.018). MCarn was higher in inactive vs. active VL (32.0±12.0 vs. 21.2±7.5 mmol‧kg-1 DM; p=0.011). In type-I fibers, MCarn was significantly higher in the inactive VL than in the active deltoid (38.3±4.7 vs. 27.3±11.8 mmol‧kg-1 DM, p=0.014). MCarn increased similarly between inactive VL and active deltoid in the β-alanine group (VL: 68.9±55.1%, p=0.0002; deltoid: 90.5±51.4%, p<0.0001), with no changes in the PL group. MCarn content was higher in the inactive VL than in the active deltoid and the active VL, but this is probably a consequence of fiber type shift (type I to type II) that occurs with chronic inactivity. Chronically inactive muscle showed an increase in MCarn after BA supplementation equally to the active muscle, suggesting that carnosine accretion following β-alanine supplementation is not influenced by muscle inactivity

Vision in high-level football officials

YesOfficiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R) and assistant referees (AR) participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9%) and ten of the 49 ARs (20.4%) were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS) and the Quality-of-Vision (QoV) questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis) were gathered in a subset (n = 44, 62%) of the participants. Data were analysed according to the type (R/AR) and level (international/national) of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of p<0.01, PVVS scores did not differ between R and AR (p = 0.88), or between national- and international-level officials (p = 0.66). Similarly, QoV scores did not differ between R and AR in frequency (p = 0.50), severity (p = 0.71) or bothersomeness (p = 0.81) of symptoms, or between international-level vs national-level officials for frequency (p = 0.03) or bothersomeness (p = 0.07) of symptoms. However, international-level officials reported less severe symptoms than their national-level counterparts (p<0.01). Overall, 18.3% of officials had either never had an eye examination or if they had, it was more than 3 years previously. Regarding refractive correction, 4.2% had undergone refractive surgery and 23.9% wear contact lenses when officiating. Clinical vision measures in the football officials were similar to published normative values for young, adult populations and similar between R and AR. Clinically-measured vision did not differ according to officiating level. Visual acuity measured with and without a pinhole disc indicated that around one quarter of participants may be capable of better vision when officiating, as evidenced by better acuity (≥1 line of letters) using the pinhole. Amongst the clinical visual tests we used, we did not find evidence for above-average performance in elite-level football officials. Although the impact of uncorrected mild to moderate refractive error upon officiating performance is unknown, with a greater uptake of eye examinations, visual acuity may be improved in around a quarter of officials.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.This project has been funded by Abbott Nutrition R&D

Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis

Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure of M. tuberculosis strains to the critical concentration of isoniazid employed for determination of drug susceptibility testing in clinical isolates. Results show that susceptible and rifampicin monoresistant strains exposed to this concentration become resistant to isoniazid after three weeks; and that resistance observed for the majority of these strains could be reduced by means of efflux pumps inhibitors. RT-qPCR assessment of efflux pump genes expression showed overexpression of all tested genes. Enhanced real-time efflux of ethidium bromide, a common efflux pump substrate, was also observed, showing a clear relation between overexpression of the genes and increased efflux pump function. Further exposure to isoniazid resulted in the selection and stabilization of spontaneous mutations and deletions in the katG gene along with sustained increased efflux activity. Together, results demonstrate the relevance of efflux pumps as one of the factors of isoniazid resistance in M. tuberculosis. These results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient from which isoniazid genetically resistant mutants emerge. Therefore, the use of inhibitors of efflux should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment

Quality of life in sarcopenia measured with the SarQoL questionnaire: A meta-analysis of individual patient data.

peer reviewedAge-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = -12.32; 95 % CI = [-15.27; -9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL

The effects of acute leucine or leucine–glutamine co-ingestion on recovery from eccentrically biased exercise

This study investigated the effects of leucine or leucine + glutamine supplementation on recovery from eccentric exercise. In a double-blind independent groups design, 23 men were randomly assigned to a leucine (0.087 g/kg; n = 8), leucine + glutamine (0.087 g/kg + glutamine 0.3 g/kg; n = 8) or placebo (0.3 g/kg maltodextrin; n = 7) group. Participants performed 5 sets of drop jumps, with each set comprising 20 repetitions. Isometric knee-extensor strength, counter-movement jump (CMJ) height, delayed-onset muscle soreness (DOMS) and creatine kinase (CK) were measured at baseline, 1, 24, 48 h and 72 h post-exercise. There was a time × group interaction for isometric strength, CMJ and CK (P < 0.05), with differences between the leucine + glutamine and placebo group at 48 h and 72 h for strength (P = 0.013; d = 1.43 and P < 0.001; d = 2.06), CMJ (P = 0.008; d = 0.87 and P = 0.019; d = 1.17) and CK at 24 h (P = 0.012; d = 0.54) and 48 h (P = 0.010; d = 1.37). The leucine group produced higher strength at 72 h compared to placebo (P = 0.007; d = 1.65) and lower CK at 24 h (P = 0.039; d = 0.63) and 48 h (P = 0.022; d = 1.03). Oral leucine or leucine + glutamine increased the rate of recovery compared to placebo after eccentric exercise. These findings highlight potential benefits of co-ingesting these amino acids to ameliorate recovery

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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