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Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer.
Cereda, E, Tancredi, R, Klersy, C, Lobascio, F, Crotti, S, Masi, S, Cappello, S, Stobäus, N, Tank, M, Cutti, S, et al
Cancer medicine. 2022;(2):308-316
Abstract
BACKGROUND Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. METHODS Data on muscle strength by handgrip (HG) dynamometry and total-body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (<10th percentiles of age and gender-specific normative values) and low total-body SMM according to SMM index cutoffs (<10.75 and <6.75 kg/m2 in men and women, respectively). RESULTS During a median follow-up of 58 months [25th-75th percentile, 37-60], 566 patients had died. Patients presenting low HG in combination or not with low SMM were characterised by shorter median survival (12.7 vs. 27.2 months, respectively; p < 0.001) compared to those with low SMM/normal HG and normal SMM/normal HG (>60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67-1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07-1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27-1.53] (p < 0.001). CONCLUSIONS Muscle weakness was found to be a more powerful predictor of survival than BIA-estimated SMM and should be considered as an additional key feature of sarcopenia in patients with cancer.
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Association of the gut microbiota and fecal short-chain fatty acids with skeletal muscle mass and strength in children.
Chen, F, Li, Q, Chen, Y, Wei, Y, Liang, J, Song, Y, Shi, L, Wang, J, Mao, L, Zhang, B, et al
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022;(1):e22109
Abstract
We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with skeletal muscle mass and strength in healthy Chinese children aged 6-9 years. In this study, 412 children were enrolled. 16S rRNA gene sequencing was used to characterize the gut microbiota compositions. Fecal SCFAs were quantified using high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the total body lean soft tissue mass (TSM), total body fat mass (TBF), appendicular skeletal muscle mass (ASM), and appendicular fat mass (AFM). TSM/height2 (TSMI), ASM/height2 (ASMI), TSM/weight (TSMR), ASM/weight (ASMR), and the ratio of TSM/TBF and ASM/AFM were calculated. Handgrip strength (HGS) was measured using the Jamar® Plus+ Hand Dynamometer. A multiple regression analysis after adjustment for covariates and multiple test correction showed some operational taxonomic units in partial least squares models identified by Multivariate methods with Unbiased Variable selection analysis such as genera of Faecalibacterium, Lachnospira, Lachnospiraceae_ND3007_group, and Lachnospiraceae_UCG-004 were positively correlated with at least one measure of TSM, TSMI, ASM, ASMI, and ASMI Z-score (β: 0.103-0.143, pFDR : .008-.032) but negatively correlated with at least one measure of TSMR, TSM/TBF, ASMR, ASM/AFM, and ASMR Z-score (β: -0.185 to 0.124, pFDR = .008-.045). Children with higher fecal butyric acid, acetic acid, and total SCFA levels exhibited higher TSM, ASM, TSMI, ASMI, and ASMI Z-score and lower TSM/TBF, ASM/AFM, TSMR, ASMR, and ASMR Z-score. However, after additional adjustment for TBF or body mass index, only the associations for Faecalitalea and Pyramidobacter still existed. Mediation analysis suggested that total body fat significantly mediated 66.3%-95.3% of the estimated association of microbiota and SCFAs with TSM, ASM, and ASMI Z-score. Our results suggest that the associations of gut microbiota and SCFAs with skeletal muscle quality in children may largely depend upon on total body fat content.
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Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.
Huang, M, Watso, JC, Belval, LN, Cimino, FA, Fischer, M, Jarrard, CP, Hendrix, JM, Laborde, CH, Crandall, CG
American journal of physiology. Regulatory, integrative and comparative physiology. 2022;(1):R55-R63
Abstract
Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.
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Therapeutic approaches to preserve the musculature in Duchenne Muscular Dystrophy: The importance of the secondary therapies.
Angelini, G, Mura, G, Messina, G
Experimental cell research. 2022;(2):112968
Abstract
Muscular dystrophies (MDs) are heterogeneous diseases, characterized by primary wasting of skeletal muscle, which in severe cases, such as Duchenne Muscular Dystrophy (DMD), leads to wheelchair dependency, respiratory failure, and premature death. Research is ongoing to develop efficacious therapies, particularly for DMD. Most of the efforts, currently focusing on correcting or restoring the primary defect of MDs, are based on gene-addition, exon-skipping, stop codon read-through, and genome-editing. Although promising, most of them revealed several practical limitations. Shared knowledge in the field is that, in order to be really successful, any therapeutic approach has to rely on spared functional muscle tissue, restricting the number of patients eligible for clinical trials to the youngest and less compromised individuals. In line with this, many therapeutic strategies aim to preserve muscle tissue and function. This Review outlines the most interesting and recent studies addressing the secondary outcomes of DMD and how to better deliver the therapeutic agents. In the future, the effective treatment of DMD will likely require combinations of therapies addressing both the primary genetic defect and its consequences.
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A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction.
Jo, D, Yoon, G, Kim, OY, Song, J
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112636
Abstract
Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed in cohort studies. Many researchers suggested that the prevalence of sarcopenia is associated with vascular disorder, such as atherosclerosis and alteration of intracellular mechanisms caused by changes in myokine secretion. We herein review the emerging evidence on the strong link between cognitive impairment and sarcopenia, focusing on myokine secretion and vascular dysfunction, and provide an understanding of the relevant mechanisms and crucial determinants in cognitive decline caused by sarcopenia.
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Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.
Sarabhai, T, Koliaki, C, Mastrototaro, L, Kahl, S, Pesta, D, Apostolopoulou, M, Wolkersdorfer, M, Bönner, AC, Bobrov, P, Markgraf, DF, et al
Diabetologia. 2022;(2):301-314
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Abstract
AIMS/HYPOTHESIS Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION ClinicalTrials.gov .NCT01736202. FUNDING German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.
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Fasting-Mimicking-Diet does not reduce skeletal muscle function in healthy young adults: a randomized control trial.
Nardon, M, Venturelli, M, Ruzzante, F, Longo, VD, Bertucco, M
European journal of applied physiology. 2022;(3):651-661
Abstract
PURPOSE The aim of this study was to evaluate the short- and long-term effects of the Fasting-Mimicking-Diet (FMD) intervention on neuromuscular parameters of force production in healthy young men. METHODS Twenty-four physically active men completed the study. Participants were randomly assigned to Fasting-Mimicking (FMD) or Normal Diet (ND) and asked to follow three cycles of dietary intervention. Neuromuscular parameters of force production during maximal voluntary isometric contractions (MVCs) with the leg extensors muscles and anthropometrics were measured at baseline (T0), at the end of the first cycle (T1), and 7-10 days after the 3rd cycle of the nutritional intervention (T2). The study was registered on Clinicaltrials.gov (No. NCT04476615). RESULTS There was a significant decrease in body mass at T1 for FMD (- 2.6 kg, ∆ from baseline, on average; p < 0.05) but not in ND (- 0.1 kg;). Neuromuscular parameters of force production, muscle volume, and MVC torque did not change or differ between groups across visits. Results were similar even when parameters were normalized by muscle volume. CONCLUSION The consumption of FMD in a group of young healthy male subjects showed to be feasible, and it did not affect neuromuscular parameters of force production. The results suggest that FMD could be safely adopted by strength athletes without detrimental effects on force and muscle volume. Further research in clinical population at risk of muscle mass loss, such as elderly and obese subjects with sarcopenia, is warranted.
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Acute Whole-Body Vibration Exercise Promotes Favorable Handgrip Neuromuscular Modifications in Rheumatoid Arthritis: A Cross-Over Randomized Clinical.
Coelho-Oliveira, AC, Lacerda, ACR, de Souza, ALC, Santos, LMM, da Fonseca, SF, Dos Santos, JM, Ribeiro, VGC, Leite, HR, Figueiredo, PHS, Fernandes, JSC, et al
BioMed research international. 2021;:9774980
Abstract
OBJECTIVE Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).
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Rationale and Design for a Higher (Dairy) Protein Weight Loss Intervention That Promotes Muscle Quality and Bone Health in Older Adults with Obesity: A Randomized, Controlled Pilot Study.
Miller, MG, Porter Starr, KN, Rincker, J, Orenduff, MC, McDonald, SR, Pieper, CF, Fruik, AR, Lyles, KW, Bales, CW
Journal of nutrition in gerontology and geriatrics. 2021;(2-3):150-170
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Abstract
In contrast to recommendations for young and middle-aged adults, intentional weight loss among older adults remains controversial and is inconsistently advised. Recent research suggests that a higher protein diet can mitigate loss of lean mass during periods of intentional weight loss among older adults with obesity; however, the effects of intentional weight loss on skeletal muscle and bone are not fully understood. The Dairy in the Diet Yields New Approaches for Muscle Optimization (DDYNAMO) trial is a 6-month, randomized, controlled pilot study assessing the effects of combining regular, generous intakes of high quality protein (30 g/meal; primarily from dairy) with caloric restriction (-500kcal/d) and low-intensity resistance exercise (30 min/3 times per week) on muscle quality, muscle composition, bone mineral density in men and women aged ≥60 years with obesity and mild to moderate functional impairment (Short Physical Performance Battery [SPPB] score ≥4 to ≤10). Participants will be re-assessed at 18 months to evaluate weight maintenance, bone mineral density, physical function, and other secondary measures. ClinicalTrials.gov Identifier: NCT02437643.
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Influence of upper limb training and analyzed muscles on estimate of physical activity during cereal grinding using saddle quern and rotary quern.
Struška, M, Hora, M, Rocek, TR, Sládek, V
PloS one. 2021;(8):e0243669
Abstract
Experimental grinding has been used to study the relationship between human humeral robusticity and cereal grinding in the early Holocene. However, such replication studies raise two questions regarding the robusticity of the results: whether female nonathletes used in previous research are sufficiently comparable to early agricultural females, and whether previous analysis of muscle activation of only four upper limb muscles is sufficient to capture the stress of cereal grinding on upper limb bones. We test the influence of both of these factors. Electromyographic activity of eight upper limb muscles was recorded during cereal grinding in an athletic sample of 10 female rowers and in 25 female nonathletes and analyzed using both an eight- and four-muscle model. Athletes had lower activation than nonathletes in the majority of measured muscles, but except for posterior deltoid these differences were non-significant. Furthermore, both athletes and nonathletes had lower muscle activation during saddle quern grinding than rotary quern grinding suggesting that the nonathletes can be used to model early agricultural females during saddle and rotary quern grinding. Similarly, in both eight- and four-muscle models, upper limb loading was lower during saddle quern grinding than during rotary quern grinding, suggesting that the upper limb muscles may be reduced to the previously used four-muscle model for evaluation of the upper limb loading during cereal grinding. Another implication of our measurements is to question the assumption that skeletal indicators of high involvement of the biceps brachii muscle can be interpreted as specifically indicative of saddle quern grinding.