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Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P

Initial definitions of sarcopenia included the age-associated loss of skeletal muscle mass that was presumed to be associated with late-life reduced functional capacity, disability and loss of independence. Because no method for determination of muscle mass was available for large cohort studies of aging men and women, lean body mass determined by dual X-ray absorptiometry or bioelectrical impedance was used as a surrogate measure of muscle mass. The data from these studies showed either no or a poor relationship between LBM and functional capacity and health related outcomes, leading to the conclusion of many that the amount of muscle may not be associated with these age-associated outcomes. It was assumed that some undefined index of muscle quality is the critical contributor. These studies also consistently showed that muscle strength is lost more quickly than lean mass. Total body muscle mass can now be measured directly, accurately and non-invasively using the D3creatine (D3Cr) dilution method. D3Cr muscle mass, but not DXA derived LBM, is strongly associated with functional capacity, falls and insulin resistance in older men and women. In addition, D3Cr muscle mass is associated with risk of disability, hip fracture and mortality. New and emerging data demonstrate that low muscle mass may serve as a diagnostic criterion for sarcopenia.

ABSTRACT Sarcopenia, characterized by an age‐related progressive loss of muscle mass and strength, presents significant health concerns. Recommending dietary nutrition emerges as a viable strategy to counteract muscle deterioration. Vitamin A, indispensable throughout the human life cycle and unattainable through endogenous synthesis, necessitates intake via diet. However, the direct correlation between sarcopenia prevalence and vitamin A intake remains unclear. This study systematically investigated the relationship between sarcopenia prevalence and vitamin A intake, including retinol and some carotenoids, across diverse races and genders utilizing multiple statistical analyses. Mixture analysis revealed significant positive correlations between total vitamin A intake and muscle mass among American adult males (Male: OR: 1.019, 95% CI: 1.010–1.027, p < 0.001). We also observed the gender‐specific results, with retinol playing a more significant role in enhancing muscle mass for males, while certain carotenoids were found to be more influential in females. Moreover, inflammation and oxidative stress mediated the relationship between vitamin A intake and sarcopenia prevalence in both genders. There may be a gender‐ and race‐specific relationship between dietary vitamin A intake and sarcopenia. Further prospective studies are imperative to elucidate the association between vitamin A intake and sarcopenia prevalence. [ABSTRACT FROM AUTHOR]

To analyse the effectiveness of resistance training on secondary sarcopenia, we conducted a meta-analysis to elucidate the effects of resistance training (RT) on muscle strength (handgrip strength [HGS]), muscle mass (Skeletal muscle mass index [SMI]), and physical function (Gait speed [GS]) in patients with secondary sarcopenia. All studies published between 2015 and January 2024 on the effects of resistance training on patients with secondary sarcopenia were retrieved from 6 electronic databases: PubMed, Web of Science Core Collection, Embase, the Cochrane Library, the China National Knowledge Infrastructure (CNKI) Core journals and the Wanfang Database. Two researchers independently extracted and evaluated studies that met the inclusion and exclusion criteria. Finally, 12 randomized controlled trials were included. Pooled analyses of baseline data and results were performed using Review Manager 5.3 with standardized mean variance (SMD) and random effects model. The study included 12 randomized controlled trials involving 639 patients (mean age 57.28 ± 2.66 to 79.6 ± 5.4 years). There are five types of complications among the patients: obesity, type 2 diabetes, Alzheimer's disease, hemodiaysis, and pancreatic cancer. Compared with the control group, RT effectively improved HGS [SMD = 2.47, 95% CI (1.50, 3.43), p < 0.01, I2 = 94%]; SMI [SMD = 0.94, 95% CI (0.52, 1.36), p < 0.01, I2 = 56%]; and GS [SMD = 2.18, 95% CI (-0.01, 4.37), p ≥ 0.05, I2 = 97%]. Further subgroup analysis of the results showed that the intervention effect on grip strength was greater for non-elastic band resistance [SMD = 2.40, 95% CI (1.05, 3.75), p < 0.01, I2 = 94%] than for elastic band resistance (EBRT) [SMD = 1.22, 95% CI (-0.14, 2.58), p < 0.01, I2 = 95%]. The intervention effect of RT on grip strength is more significant in patients with T2D [SMD = 0.59, 95%CI (0.26–0.93, p < 0.01, I2 = 27%] and obesity [SMD = 0.74, 95%CI (0.32–1.15, p < 0.01, I2 = 0%]. For patients with secondary sarcopenia, Resistance training (RT) can effectively enhance muscle strength and muscle mass; however, it does not significantly improve physical function. Different RT intervention methods have different effects on patients, such as elastic band training and non-elastic band training (bounce ball RT; equipment RT, etc.). Different types of complications may influence the effectiveness of RT intervention. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of serum creatinine-cystatin C ratio (Cr/CysC) with long-term all-cause mortality and cause-specific (cardiovascular and cancer) mortality among US general adults. Methods: This nationally representative cohort study included adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Participants were linked to National Death Index data from the survey date through December 31, 2019. Weighted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs), and restricted cubic splines and stratified analyses were also performed. Results: A total of 12,914 participants were included in this study (mean [SD] age, 45.3 [17.3] years; males, 48.9%). During a median follow-up of 17.9 years (maximum follow-up, 20.8 years), 3439 total deaths occurred, including 1098 cardiovascular deaths and 736 cancer deaths. Cumulative incidence curves revealed that increased Cr/CysC ratio had lower risk of all-cause (P < 0.001), cardiovascular (P < 0.001) and cancer (P < 0.001) mortality. Cox regression an Fine-Gray hazards models demonstrated that the multivariable-adjusted hazard ratios comparing the highest vs. lowest quartile of Cr/CysC ratio were 0.40 (95% CI, 0.34–0.47; P < 0.001) for all-cause mortality, 0.68 (95% CI, 0.52–0.88; P < 0.001) for cardiovascular mortality, and 0.51 (95% CI, 0.36–0.71; P < 0.001) for cancer mortality. Nonlinear association was observed for Cr/CysC ratio and all-cause mortality (P = 0.018 for nonlinearity), and linear associations were observed for Cr/CysC ratio and cardiovascular (P = 0.212 for nonlinearity) and cancer (P = 0.550 for nonlinearity) mortality. Besides, a series of sensitivity analyses ensured the robustness of the results. Conclusions: In this cohort of US adults, Cr/CysC ratio was negatively associated with all-cause, cardiovascular, and cancer mortality. Our study suggests that Cr/CysC ratio may serve as a simple and effective predictor of long-term health outcomes. [ABSTRACT FROM AUTHOR]

Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982–0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032–1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045–1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65 years (CCR tertile 1: HR = 1.916, 95% CI: 1.366–2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267–2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS. [ABSTRACT FROM AUTHOR]

Tetrandrine (Tet), a well-known drug of calcium channel blocker, has been broadly applied for anti-inflammatory and anti-fibrogenetic therapy. However, due to the functional diversity of ubiquitous calcium channels, potential side-effects may be expected. Our previous report revealed an inhibitory effect of Tet on myogenesis of skeletal muscle. Here, we found that Tet induced protein degradation resulting in the myofibril atrophy. Upon administration with a relative high dose (40 mg/kg) of Tet for 28 days, the mice displayed significantly reduced muscle mass, strength force, and myosin heavy chain (MyHC) protein levels. The MyHC reduction was further detected in C2C12 myotubes after treating with Tet. Interestingly, the expression of Atrogin-1 and Murf-1, the skeletal muscle specific E3 ligases of protein ubiquitin–proteasome system (UPS), was accordingly up-regulated, and the reduced MyHC was significantly mitigated by MG132, a 26S proteasome inhibitor, indicating a key role of UPS in the protein degradation of muscle cells. Further study showed that Tet induced autophagy also participated in the protein degradation. Mechanistically, Tet treatment caused ROS production in myotubes that in turn targeted on FoxO3/AKT signaling, resulting in the activation of UPS and autophagy processes that were involved in the protein degradation. Our study reveals a potential side-effect of Tet on skeletal muscle atrophy, particularly when the drug dose is relatively high. [ABSTRACT FROM AUTHOR]

Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P < 0.001). Additionally, we also found that lower PA was associated with higher CV risk scores. The PA detected by bioelectrical impedance analysis could predict the risk of PEW and cardiovascular events among patients with MHD. When used in conjunction, PA, ASMI, BCM, and MAC have a high diagnostic efficacy for PEW in patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

This study aims to understand the metabolic mechanisms of unintentional weight loss in older adults. We investigated plasma metabolite associations of subsequent weight change over 2 years in 1536 previously weight stable participants (mean age 74.6 years, 50% women, 35% Black) from the Health, Aging and Body Composition (Health ABC) Study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss with/without an intention and weight gain >3% annually relative to weight stability. The metabolite associations of unintentional weight loss differed from those of intentional weight loss and weight gain. Lower levels of aromatic amino acids, phospholipids, long‐chain poly‐unsaturated triglycerides, and higher levels of amino acid derivatives, poly‐unsaturated fatty acids, and carbohydrates were associated with higher odds of unintentional weight loss after adjusting for age, sex, race, and BMI categories. Prevalent diseases attenuated four and lower mid‐thigh muscle mass and poorer appetite each attenuated 2 of 77 identified metabolite associations by >20%, respectively. Other factors (e.g., energy expenditure, diet, and medication) attenuated all associations by <20%. While 16 metabolite associations were attenuated by 20%–48% when adjusting for all these risk factors, 47 metabolite associations remained significant. Altered amino acid metabolism, impaired mitochondrial fatty acid oxidation, and inflammaging implicated by identified metabolites appear to precede unintentional weight loss in Health ABC older adults. Furthermore, these pathways seem to be associated with prevalent diseases especially diabetes, lower muscle mass, and poorer appetite. [ABSTRACT FROM AUTHOR]

Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in complex with LRPPRC, is a PGC-1α target that regulates mitochondrial structure, respiration, and mtDNA-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracts mitochondrial defects caused by genetically-induced LRPPRC/SLIRP loss, despite sustained low mtDNA-encoded-mRNA pools, by increasing mitoribosome translation capacity and mitochondrial quality control. In humans, exercise training robustly increases muscle SLIRP and LRPPRC protein across exercise modalities and sexes, yet less prominently in individuals with type 2 diabetes. SLIRP muscle loss reduces Drosophila lifespan. Our data points to a mechanism of post-transcriptional mitochondrial regulation in muscle via mitochondrial mRNA stabilization, offering insights into how exercise enhances mitoribosome capacity and mitochondrial quality control to alleviate defects. Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle. [ABSTRACT FROM AUTHOR]

Background: Although pancreaticoduodenectomy (PD) for pancreatic or periampullary cancer is the gold standard treatment regardless of patient age, patients aged 80 years or older have poor postoperative short-term outcomes because of their poor functional status and many medical comorbidities. Postoperative rehabilitation in octogenarians could improve postoperative outcomes; however, its effect remains unclear. Methods: This retrospective study included patients who underwent PD at two institutions between January 2019 and December 2022. All patients were managed using the enhanced recovery after surgery (ERAS) protocol, and elderly patients or those with loss of muscle mass or frailty underwent additional perioperative rehabilitation. Postoperative short-term outcomes were compared between the octogenarians and non-octogenarians. Results: We reviewed 251 patients including 44 octogenarians (17.5%). Octogenarians had higher rates of comorbidity (78.9% vs. 55.1%, P = 0.049) and sarcopenia (31.8% vs. 16.4%, P = 0.018) and a more impaired nutritional status than non-octogenarians and received postoperative rehabilitation more frequently (86.4% vs. 44.0%, P < 0.001, respectively). Under the rehabilitation-enhanced ERAS protocol, the postoperative major complication rate (25.0% vs. 24.6%, P = 0.960), the length of hospital stay (LOS) (P = 0.435), and the length of functional recovery (LOFR) (P = 0.110) did not differ between the two groups. In the multivariate analysis, age ≥ 80 years was not determined as a risk factor for major complications. Conclusions: Despite the poor functional and nutritional status of octogenarians, their postoperative major complication rates, LOS, and LOFR after PD were comparable with those of non-octogenarians under the rehabilitation-enhanced ERAS protocol. [ABSTRACT FROM AUTHOR]

Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric techniques, demonstrating potential limitations with level-based approaches for assessing outcomes. In addition, we identify gene expression signatures in normal kidney that correlate with fat and muscle body composition traits that can be used to predict sex-specific outcomes in renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that the insulin-sensitizing adipokine adiponectin (ADP) is upregulated in cystic fibrosis (CF) related diabetes (CFRD) and underweight adults with CF. We aimed to assess correlations between glucose metabolism, body composition and ADP in CF. Methods: We performed a cross-sectional study among adults with CF at the Copenhagen CF Center. The study included a fasting level of ADP, an oral glucose tolerance test (OGTT), and a dual energy-x-ray absorptiometry scan. Results: In total, 115 patients were included of whom 104 had an OGTT performed. Glucose intolerance was not correlated with ADP in multivariable analysis, while increased hepatic insulin resistance (i.e., HOMA-IR) was correlated with reduced ADP levels. ADP declined by 4% (eβ 0.96, 95% CI: 0.94, 0.98), 5% (eβ 0.95, 95% CI: 0.93, 0.98), 9% (eβ 0.91, 95% CI: 0.87, 0.95), and 83% (eβ 0.17, 95% CI: 0.08, 0.37) for each one unit (kg/m2) increase in body mass index, fat mass index, muscle mass index, and bone mineral content index, respectively. Conclusions: In CF, ADP was negatively correlated with hepatic insulin resistance as well as low fat, muscle, and bone mass, but not with glucose intolerance. This suggests that malnutrition leads to higher ADP levels in CF. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (SCI) results in the disruption of physiological systems below the level of the spinal lesion. Connexin hemichannels (CxHCs) are membrane-bound, non-selective pore proteins that are lost in mature myofibers but reappear de novo on the sarcolemma after peripheral denervation, chronic SCI, diabetes, and severe systemic stress such as sepsis. Cx43 and Cx45 have been implicated as the major CxHCs present in diseased muscle, and muscle-restricted knockout of these genes reduces muscle atrophy after denervation, likely by reducing excess calcium influx with resultant inflammasome activation. A muscle-restricted Cx43/45 conditional knockout (mKO) mouse model was developed and tested to check whether it would improve outcomes following either a complete spinal cord transection at the level of thoracic vertebrae-9 (T9) or a motor-incomplete T9 impact-contusion SCI. mKO had no effect on the body mass after complete T9 transection. There was reduced atrophy of the plantaris 15 days post-SCI that was not associated with molecular markers of inflammation, hypertrophic/atrophic protein signaling, or protein and mRNA expression related to mitochondrial integrity and function. mKO mice had faster and greater locomotor recovery across 28 days after a motor-incomplete contusion SCI with no differences in spared white matter; male mKO mice generally had greater muscle mass than genotype controls post-injury, but muscle sparing was not observed in female mKO mice post-injury. The data establish a new paradigm where muscle Cx43/45 may contribute to the tissue crosstalk that determines the neuromuscular function of sub-lesional musculature after motor-incomplete SCI in a sex-dependent manner. Our novel findings should promote investigation to develop innovative treatment strategies to improve the function and quality of life for persons with SCI. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs), also known as fibro‐adipogenic progenitors, play a critical role in muscle maintenance and sarcopenia development. Although analogous MSCs are present in various tissues, recent single‐cell RNA‐seq studies have revealed the inter‐tissue heterogeneity of MSCs. However, the functional significance of MSC heterogeneity and its role in aging remain unclear. Here, we investigated the properties of MSCs and their age‐related changes in seven mouse tissues through histological, cell culture, and genetic examinations. The tissue of origin had a greater impact on the MSC transcriptome than aging. By first analyzing age‐related changes, we found that Kera is exclusively expressed in muscle MSCs and significantly down‐regulated by aging. Kera knockout mice recapitulated some sarcopenic phenotypes including reduced muscle mass and specific force, revealing the functional importance of Kera in the maintenance of muscle youth. These results suggest that MSCs have tissue‐specific supportive functions and that deterioration in these functions may trigger tissue aging. [ABSTRACT FROM AUTHOR]

Sarcopenia, a leading cause for global disability and mortality, is an age‐related muscular disorder, characterized by accelerated muscle mass loss and functional decline. It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating β‐hydroxybutyrate (β‐HB) levels. Whether the elevated β‐HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans and mouse models that an increase of β‐HB reverse myofiber atrophy and improves motor functions at advanced ages. β‐HB‐induced histone lysine β‐hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that β‐HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a state with a progressive and generalized loss of skeletal muscle mass and strength. However, muscle strength and muscle mass are different features, which are usually not studied separately. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in chronic kidney disease (CKD). Methods: The study sample consisted of 84 patients with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS). Muscle quantity was measured with bioimpedance spectroscopy (BIS). Serum creatinine, urea, uric acid (UA), and albumin were measured as well. Results: Appendicular skeletal muscle mass (ASM) significantly and positively correlated with body mass, NH weight (normally hydrated weight), height, body mass index (BMI), lean tissue mass (LTM), lean tissue index (LTI), fat mass (FM), and fat tissue index (FTI), and was negatively associated with hydration status. HGS significantly and positively correlated with body mass, NH weight, height, LTM, LTI, and ASM, and was negatively associated with UA and urea. After adjustment for age, sex, and height, HGS remained significantly and negatively related with UA and hydration status. Conclusions: In CKD patients, ASM is determined by anthropometric parameters, but HGS is determined by both anthropometric and clinical variables specific for CKD. In order to study the determinants of HGS in CKD, relationships with HGS should be adjusted for anthropometric variables. [ABSTRACT FROM AUTHOR]

Aspiration pneumonia exacerbates swallowing and respiratory muscle atrophy. It induces respiratory muscle atrophy through three steps: proinflammatory cytokine production, caspase-3 and calpain, and then ubiquitin–proteasome activations. In addition, autophagy induces swallowing muscle atrophy. Nrf2 is the central detoxifying and antioxidant gene whose function in aspiration pneumonia is unclear. We explored the role of Nrf2 in aspiration pneumonia by examining swallowing and respiratory muscle mass and function using wild-type and Nrf2-knockout mice. Pepsin and lipopolysaccharide aspiration challenges caused aspiration pneumonia. The swallowing (digastric muscles) and respiratory (diaphragm) muscles were isolated. Quantitative RT-PCR and Western blotting were used to assess their proteolysis cascade. Pathological and videofluoroscopic examinations evaluated atrophy and swallowing function, respectively. Nrf2-knockouts showed exacerbated aspiration pneumonia compared with wild-types. Nrf2-knockouts exhibited more persistent and intense proinflammatory cytokine elevation than wild-types. In both mice, the challenge activated calpains and caspase-3 in the diaphragm but not in the digastric muscles. The digastric muscles showed extended autophagy activation in Nrf2-knockouts compared to wild-types. The diaphragms exhibited autophagy activation only in Nrf2-knockouts. Nrf2-knockouts showed worsened muscle atrophies and swallowing function compared with wild-types. Thus, activation of Nrf2 may alleviate inflammation, muscle atrophy, and function in aspiration pneumonia, a major health problem for the aging population, and may become a therapeutic target. [ABSTRACT FROM AUTHOR]

Sarcopenia is a systemic medical disorder characterized by a gradual decline in muscular strength, function, and skeletal muscle mass. Currently, there is no medication specifically approved for the treatment of this condition. Therefore, the identification of new pharmacological targets may offer opportunities for the development of novel therapeutic strategies. The current in silico study investigated the active ingredients and the mode of action of Citri Reticulatae Pericarpium (CRP) in addressing sarcopenia. The active ingredients of CRP and the potential targets of CRP and sarcopenia were determined using various databases. The STRING platform was utilized to construct a protein–protein interaction network, and the key intersecting targets were enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Molecular docking was used to determine the binding interactions of the active ingredients with the hub targets. The binding affinities obtained from molecular docking were subsequently validated through molecular dynamics simulation analyses. Five active ingredients and 45 key intersecting targets between CRP and sarcopenia were identified. AKT1, IL6, TP53, MMP9, ESR1, NFKB1, MTOR, IGF1R, ALB, and NFE2L2 were identified as the hub targets with the highest degree node in the protein–protein interaction network. The results indicated that the targets were mainly enriched in PIK3-AKT, HIF-1, and longevity-regulating pathways. The active ingredients showed a greater interaction affinity with the hub targets, as indicated by the results of molecular docking and molecular dynamics simulations. Our findings suggest that the active ingredients of Citri Reticulatae Pericarpium, particularly Sitosterol and Hesperetin, have the potential to improve sarcopenia by interacting with AKT1 and MTOR proteins through the PI3K-AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy caused by denervation is common in neuromuscular diseases, leading to loss of muscle mass and function. However, a comprehensive understanding of the overall molecular network changes during muscle denervation atrophy is still deficient, hindering the development of effective treatments. Method: In this study, a sciatic nerve transection model was employed in male C57BL/6 J mice to induce muscle denervation atrophy. Gastrocnemius muscles were harvested at 3 days, 2 weeks, and 4 weeks post-denervation for transcriptomic and proteomic analysis. An integrative multi-omics approach was utilized to identify key genes essential for disease progression. Targeted proteomics using PRM was then employed to validate the differential expression of central genes. Combine single-nucleus sequencing results to observe the expression levels of PRM-validated genes in different cell types within muscle tissue.Through upstream regulatory analysis, NRF2 was identified as a potential therapeutic target. The therapeutic potential of the NRF2-targeting drug Omaveloxolone was evaluated in the mouse model. Result: This research examined the temporal alterations in transcripts and proteins during muscle atrophy subsequent to denervation. A comprehensive analysis identified 54,534 transcripts and 3,218 proteins, of which 23,282 transcripts and 1,852 proteins exhibited statistically significant changes at 3 days, 2 weeks, and 4 weeks post-denervation. Utilizing multi-omics approaches, 30 hubgenes were selected, and PRM validation confirmed significant expression variances in 23 genes. The findings highlighted the involvement of mitochondrial dysfunction, oxidative stress, and metabolic disturbances in the pathogenesis of muscle atrophy, with a pronounced impact on type II muscle fibers, particularly type IIb fibers. The potential therapeutic benefits of Omaveloxolone in mitigating oxidative stress and preserving mitochondrial morphology were confirmed, thereby presenting novel strategies for addressing muscle atrophy induced by denervation. GSEA analysis results show that Autophagy, glutathione metabolism, and PPAR signaling pathways are significantly upregulated, while inflammation-related and neurodegenerative disease-related pathways are significantly inhibited in the Omaveloxolone group.GSR expression and the GSH/GSSG ratio were significantly higher in the Omaveloxolone group compared to the control group, while MuSK expression was significantly lower than in the control group. Conclusion: In our study, we revealed the crucial role of oxidative stress, glucose metabolism, and mitochondrial dysfunction in denervation-induced muscle atrophy, identifying NRF2 as a potential therapeutic target. Omaveloxolone was shown to stabilize mitochondrial function, enhance antioxidant capacity, and protect neuromuscular junctions, thereby offering promising therapeutic potential for treating denervation-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: This study's purpose was to evaluate the relationship between dance training volume, body composition, and habitual diet in female collegiate dancers. Methods: Thirty-three female collegiate dancers from three dance programs (20.4 ± 1.05 yrs.; 165.4 ± 11.3 cm, BMI 21.3 ± 3.4 kg/m2) participated in "The Intercollegiate Artistic Athlete Research Assessment (TIAARA)" study. We assessed dance training volume, body composition, and habitual diet. Data were analyzed using descriptive statistics (means ± SD). Two-sample t-tests were conducted to compare reported intake values versus sports nutrition recommendations. Two-tailed Pearson correlations (r) were computed for body composition and dietary intake (p < 0.05). Results: Collegiate dancers were enrolled in 16 ± 2.09 semester credits, with 7.7 ± 3.8 credits as dance movement courses and an additional 3.0 ± 1.5 h/week of rehearsal time. Body composition assessments included fat mass (24.4 ± 6.8%), lean mass (LM) (42.4 ± 10.1 kg), and total body water (32.6 ± 4.6 L). Habitual diets reflected a low-calorie diet (1399 ± 648 kcal/d), with ~20% of dancers consuming a very low-calorie diet (≤1000 kcal/d). Dancers reported under-consuming dietary protein (54.3 ± 26.2 g) and carbohydrate (171.8 ± 77.8 g). LM was positively correlated with daily total energy (r = 0.333), fat (r = 0.37), protein (r = 0.349), and leucine intake (r = 0.352). Conclusions: Our findings emphasize the positive effect of adequate nutritional quantity and quality on body composition in female collegiate dancers. [ABSTRACT FROM AUTHOR]

Background/Objectives: The loss of muscle mass is common in critically ill patients and is associated with poor prognosis, and efforts have been made to mitigate muscle loss through rehabilitation. This study aimed to evaluate changes in muscle mass in critically ill patients following rehabilitation. Methods: We enrolled 53 patients expected to stay in the ICU for more than 7 days, dividing them into rehabilitation (15 patients) and no rehabilitation groups (38 patients). Muscle mass was measured using ultrasound and bioelectrical impedance analysis (BIA). Results: Baseline characteristics and comorbidities showed no statistical differences between the two groups. Initial measurements of muscles showed no significant differences between the groups in rectus femoris thickness, total anterior thigh muscle thickness, cross-sectional area, echogenicity, or in-body skeletal muscle mass at baseline and 7 days. However, at 14 days, significant differences emerged. The rehabilitation group had greater rectus femoris thickness (1.42 cm vs. 0.81 cm, p = 0.007) and total anterior thigh muscle thickness (3.79 cm vs. 2.32 cm, p = 0.007) compared to the no rehabilitation group. Additionally, the rehabilitation group experienced a significantly smaller reduction in rectus femoris cross-sectional area (−4.6% vs. −22.8%, p = 0.021). Although survival rates were higher in the rehabilitation group (73.3% vs. 52.6%), this difference was not statistically significant (p = 0.096). Conclusions: Our findings suggest that rehabilitation in critically ill patients is associated with a slower rate of muscle loss, particularly in the cross-sectional area of the rectus femoris muscle, which may be beneficial for patient recovery. [ABSTRACT FROM AUTHOR]

This systematic review investigates the potential of bergamot, a polyphenol-rich citrus fruit, in improving osteosarcopenic obesity, a condition characterized by the simultaneous presence of osteoporosis, obesity, and sarcopenia. Bergamot extracts have been suggested to possess several pharmacological properties, including anti-inflammatory and antioxidant effects, which could be useful in the management of age-related diseases and neuromuscular health. The review highlights the promising effects of bergamot extracts on skeletal muscle mass and function, particularly in the context of obesity, metabolic syndrome, osteosarcopenic obesity, and osteoporosis. Furthermore, some studies have shown that bergamot extracts can improve the metabolic balance, endothelial function, and maximal oxygen uptake in athletes, highlighting their potential benefits for skeletal muscle health. Taken together, these results suggest that bergamot extracts, especially those rich in polyphenols, may be a valuable adjunct in the management of osteosarcopenic obesity and other associated clinical conditions involving pro-inflammatory effects on organs and tissues. [ABSTRACT FROM AUTHOR]

Background: Hepatic resection of Klatskin tumors usually requires postoperative intensive care unit (ICU) admission because of its high morbidity and mortality. Identifying surgical patients who will benefit most from ICU admission is important because of scarce resources but remains difficult. Sarcopenia is characterised by the loss of skeletal muscle mass and is associated with poor surgical outcomes. Methods: We retrospectively analysed the relationship between preoperative sarcopenia and postoperative ICU admission and length of ICU stay (LOS-I) in patients who underwent hepatic resection for Klatskin tumors. Using preoperative computed tomography scans, the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra was measured and normalised to the patient's height. Using these values, the optimal cut-off for diagnosing sarcopenia was determined using receiver operating characteristic curve analysis for each sex. Results: Of 330 patients, 150 (45.5%) were diagnosed with sarcopenia. Patients with preoperative sarcopenia presented significantly more frequently to the ICU (77.3% vs. 47.9%, p < 0.001) and had longer total LOS-I (2.45 vs 0.89 days, p < 0.001). Moreover, patients with sarcopenia showed a significantly higher postoperative length of hospital stay, severe complication rate, and in-hospital mortality. Conclusions: Sarcopenia correlated with poor postoperative outcomes, especially with the increased requirement of postoperative ICU admission and prolonged LOS-I after hepatic resection in patients with Klatskin tumors. [ABSTRACT FROM AUTHOR]

Background: A newly developed technique, the Triglyceride-glucose (TyG) index, supplies a more straightforward method to identify IR than the HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). Yet no methodical analysis has looked into the link involving the TyG index and low muscle mass (LMM), low muscle strength (LMS), and sarcopenia within the US. Thus, this study intended to find any connection concerning the TyG index and LMM, LMS, and sarcopenia. Methods: Between 2011 to 2014, data from the NHANES were used to conduct a nationally representative study involving 2,504 participants. LMM, LMS, and sarcopenia were the outcome variables. Moreover, this positive correlation persists irrespective of age and gender. Results: The TyG index revealed a significant correlation with the prevalence of developing LMM (OR = 1.63(1.26–2.11), p=0.001), LMS (OR = 1.61(1.36–1.91), p<0.001) and sarcopenia (OR = 1.59 (1.23–2.07), p<0.001), after correcting for all variables. Utilizing smooth curve fitting alongside two-piecewise linear regression models, an inverted U-shaped correlation between the TyG index and the prevalence of LMM, LMS, and sarcopenia. Finally, subgroup analysis revealed that the association between the TyG index and LMM, LMS, and sarcopenia was particularly evident in all gender, age subgroups, and individuals with a normal BMI of 25. Conclusion: Sarcopenia and the TyG index reveal an essential positive link. It highlights the potential utility of the TyG index as a screening tool for identifying individuals at risk of sarcopenia earlier. [ABSTRACT FROM AUTHOR]

Aim: Dysphagia often develops after esophagectomy. The geniohyoid muscle is involved in swallowing movements, but its significance in esophagectomy patients remains unclear. We investigated the relationship of preoperative geniohyoid muscle mass with post‐esophagectomy swallowing function. Method s : We retrospectively analyzed 114 patients who underwent esophagectomy and gastric conduit reconstruction for esophageal malignancy. We evaluated preoperative geniohyoid muscle sagittal cross‐sectional areas (cm2) using computed tomography. Median values for each sex were considered as cutoff values. Dysphagia severity was assessed using the Penetration–Aspiration Scale (PAS) during video‐fluoroscopic swallowing studies performed 7–10 days postoperatively. Results: The cross‐sectional area was significantly larger in males than in females (3.2 ± 0.7 vs. 2.4 ± 0.5, p < 0.01: median in males: 3.2 cm2, and in females: 2.3 cm2). These values were used to define high and low cross‐sectional area groups. The cross‐sectional area correlated positively with grip strength (correlation coefficient (CC) = 0.530) and skeletal muscle index (CC = 0.541). Transthyretin levels (22.4 ± 6.8 vs. 25.4 ± 5.5, p = 0.03) and cross‐sectional area (2.6 ± 0.7 vs. 3.2 ± 0.8, p < 0.01) were significantly lower in patients with (PAS score ≥6; 20%) than in those without aspiration during fluoroscopic swallowing studies. Recurrent laryngeal nerve palsy was significantly more frequent in those with than in those without aspiration during fluoroscopic studies (22% vs. 5%, p = 0.03). In the multivariate analysis, low cross‐sectional area and recurrent laryngeal nerve palsy were both independent risk factors for aspiration during swallowing studies (odds ratio = 3.6, p = 0.03 and odds ratio = 6.6, p = 0.02, respectively). Conclusion: Preoperative geniohyoid muscle mass, evaluated using neck computed tomography, can predict dysphagia after esophagectomy. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength. Transitioning from pediatric to adult care presents challenges, including accurately identifying candidates for continued GH therapy, reevaluating persistent GHD, and preventing treatment discontinuation. Assessing readiness for transition and self-management skills is crucial. This Policy and Practice Review provides a comprehensive overview of current policies, regulations, and guidelines pertinent to managing GHD transition in Belgium. We integrate perspectives from national academic and nonacademic clinical stakeholders in pediatric and adult endocrine care to provide an updated policy framework. This framework underscores the importance of sustained GH therapy during transition, particularly for individuals with persistent GHD, with the goal of optimizing practices and improving outcomes during this critical period. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, affects 20-25% of the global population. The creatinine-to-cystatin C ratio (CCR) is an indicator of skeletal muscle mass. While CCR may play a role in MetS development, sex differences in these associations are not fully understood. Therefore, this study aimed to investigate how CCR levels are associated with MetS in a Chinese adult population, focusing on possible sex disparities. Method: We conducted a retrospective cross-sectional analysis of 9,376 adults from Xiamen Chang Gung Hospital between 2014 to 2016. We examined the relationship between CCR and MetS, adjusting for cardiometabolic risk factors. Results: The prevalence of MetS was 24.7% in males and 18.0% in females. Interestingly, we observed significant sex differences in the association between CCR quartiles and MetS. Females in the lowest CCR quartile had a significantly higher risk of MetS (odds ratio=1.84). Receiver operating characteristic curve analysis revealed acceptable diagnostic power of CCR for MetS in females (area under the curve=0.65) but not in males. Conclusion: Our findings suggest that CCR is an independent risk factor for MetS in females, highlighting the importance of sex-specific assessments when evaluating MetS risk. [ABSTRACT FROM AUTHOR]

Background: In recent years, the African spiny mouse Acomys cahirinus has been shown to regenerate a remarkable array of severe internal and external injuries in the absence of a fibrotic response, including the ability to regenerate full-thickness skin excisions, ear punches, severe kidney injuries, and complete transection of the spinal cord. While skeletal muscle is highly regenerative in adult mammals, Acomys displays superior muscle regeneration properties compared with standard laboratory mice following several injuries, including serial cardiotoxin injections of skeletal muscle and volumetric muscle loss (VML) of the panniculus carnosus muscle following full-thickness excision injuries. VML is an extreme muscle injury defined as the irrecoverable ablation of muscle mass, most commonly resulting from combat injuries or surgical debridement. Barriers to the treatment of VML injury include early and prolonged inflammatory responses that promote fibrotic repair and the loss of structural and mechanical cues that promote muscle regeneration. While the regeneration of the panniculus carnosus in Acomys is impressive, its direct relevance to the study of VML in patients is less clear as this muscle has largely been lost in humans, and, while striated, is not a true skeletal muscle. We therefore sought to test the ability of Acomys to regenerate a skeletal muscle more commonly used in VML injury models. Methods: We performed two different VML injuries of the Acomys tibialis anterior muscle and compared the regenerative response to a standard laboratory mouse strain, Mus C57BL6/J. Results: Neither Acomys nor Mus recovered lost muscle mass or myofiber number within three months following VML injury, and Acomys also failed to recover force production better than Mus. In contrast, Acomys continued to express eMHC within the injured area even three months following injury, whereas Mus ceased expressing eMHC less than one-month post-injury, suggesting that Acomys muscle was primed, but failed, to regenerate. Conclusions: While the panniculus carnosus muscle in Acomys regenerates following VML injury in the context of full-thickness skin excision, this regenerative ability does not translate to regenerative repair of a skeletal muscle. [ABSTRACT FROM AUTHOR]

Aging has made stroke a top killer and disabler, with post-stroke sarcopenia worsening disability and quality of life. While resistance training benefits the elderly, its impact on stroke patients is understudied. This study evaluates the potential of a 4-week unilateral resistance training (URT) program to prevent sarcopenia in stroke patients. It assesses the impact of URT on hand grip strength (HG), muscle thickness (MT), upper limb functionality, and the psychological status of the patients. The study aims to quantitatively analyze these indicators to inform evidence-based post-stroke rehabilitation practices. This study employed a randomized controlled trial (RCT) involving 77 eligible stroke survivors, equally allocated into a control group (n = 39) and an intervention group (n = 38). The control group received standard rehabilitation, while the intervention group additionally underwent a 4-week URT program. The primary outcomes were unaffected side HG and MT, measuring muscle mass and function. Secondary outcomes included the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) for upper limb functionality and the Hamilton Depression Rating Scale (HAMD) for psychological well-being changes. Statistical analysis showed significant differences (p < 0. 05) in all measured parameters between the intervention and control groups after the 4-week period. Intra-group comparisons also indicated substantial improvements (p < 0. 05). Unilateral resistance training significantly mitigates muscle atrophy in stroke patients, preventing sarcopenia and enhancing upper limb function. It also ameliorates depressive symptoms, improving rehabilitation outcomes and overall quality of life. [ABSTRACT FROM AUTHOR]

Sarcopenia, defined as age-associated loss of skeletal muscle function and muscle mass, is a negative prognostic marker for survival in several tumor entities. However, data evaluating the impact of sarcopenia and fat distribution on penile cancer are rarely described. We performed a retrospective study including 38 patients who were diagnosed with squamous cell carcinoma of the penis. By measuring skeletal muscle mass and fat distribution at axial abdominal computed tomography images at the third lumbar vertebra several body composition parameters including skeletal muscle index (SMI), psoas muscle index (PMI), visceral obesity and visceral-to-subcutaneous fat ratio were determined. Among 38 patients, 26% (n = 10) of the patients with penile cancer were identified as sarcopenic. SMI, age, lymph node metastases, distant metastases and penile cancer of the shaft were identified as significant risk factors for overall survival. PMI and distant metastases were significantly associated with cancer specific survival. None of the analysed adipose tissue parameters could be identified as risk factors for survival in this study. We showed that sarcopenia occurs in a relevant part of patients with penile cancer and is a significant risk factor for overall survival (p = 0.032) and cancer specific survival (p = 0.034) for patients with penile cancer. Regarding fat distribution further studies are needed to evaluate its impact on sarcopenia and survival. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, the progressive loss of muscle mass and strength, is common among patients with chronic kidney disease, especially those on maintenance hemodialysis. This condition often arises from factors like reduced physical activity and metabolic changes associated with chronic kidney disease. This study aims to assess the prevalence and severity of sarcopenia in patients on maintenance hemodialysis (MHD), focusing on probable sarcopenia and its correlations with physical activity, body mass index, and inorganic phosphorus levels. Methods: This cross-sectional study involved 220 patients on MHD who visited to West China Hospital of Sichuan University between February and April 2023. The demographic data, body measurements, and laboratory results were retrospectively collected. Sarcopenia was assessed using the 2019 criteria from the Asian Working Group and the European Working Group on Sarcopenia in Older People, and physical activity was measured via the International Physical Activity Questionnaire. Results: Of the study participants, 141 (64.1%) were diagnosed with probable [110 (50.0%) or confirmed sarcopenia [31 (14.1%)], including 22 (10%) with severe sarcopenia. Multivariable logistic regression analysis revealed that physical activity (International Physical Activity Questionnaire score, OR = 0.998, 95% CI: 0.998–0.999, P < 0.001), body mass index (OR = 0.868, 95% CI: 0.788–0.957, P = 0.004), and inorganic phosphorus levels (OR = 0.513, 95% CI: 0.270–0.975, P = 0.042) independently influenced the likelihood of sarcopenia. Within the sarcopenic group, physical activity and BMI significantly correlated with the condition's severity. Conclusion: The prevalence of probable or confirmed sarcopenia in patients on MHD is significant. Factors such as physical activity, body mass index, and inorganic phosphorus levels are independently associated the presence and severity of sarcopenia in this population. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100051111), registered on 2021–09–13. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia has been shown to be an important condition with the ability to predict negative health outcomes, especially in hospitalized older adults; hence, its accurate identification has an important role in the prognosis of older patients. Aim: The prevalence of sarcopenia among hospitalized older adults was assessed by employing three distinct diagnostic methods. Methods: Older adults who were hospitalized were recruited. Bioelectrical impedance analysis was used to assess muscle mass and body composition. Sarcopenia was diagnosed via the European and Asian criteria and via a modified approach in which the Colombian cutoff points for handgrip and gait speed were used. Finally, a cluster analysis was performed to classify the population. Results: The prevalence rates of sarcopenia and severe sarcopenia ranged from 7.3 to 31.6%. The agreement between approaches revealed substantial or almost perfect agreement in 30% of the sarcopenia comparisons and 46.6% of the severe sarcopenia comparisons. The cluster analysis defined three different clusters. The first cluster was associated with increased age, BMI and body fat and poorer functional status and muscle. The second cluster was the healthiest, with high functional status and muscle mass. The third cluster had intermediate characteristics. Discussion: This study highlights the requirements for standardized diagnostic criteria and precise body composition assessment tools in acute geriatric units and highlights the heterogeneity of older adults. Accurate assessment and well-defined diagnostic criteria will facilitate the implementation of appropriate management and interventions. Conclusion: Sarcopenia is highly prevalent in hospitalized older adults, but the adjusted criteria and the inclusion of other parameters must be considered in the assessment. [ABSTRACT FROM AUTHOR]

The gold standard to estimate muscle mass and quality is computed tomography (CT) scan. Lower mass and density (intramuscular fat infiltration) of skeletal muscles are markers of sarcopenia, associated with increased mortality risk, impaired physical function, and poorer prognosis across various populations and medical conditions. We aimed to describe standard reference values in healthy population, prospective kidney donors, and correlate clinical parameters to muscle mass and density. Included in the cohort 384 consecutive kidney donors. Mean age was 44.6 ± 11.5 (range 18.4–74.2), 46% were female and mean BMI was 25.6 ± 3.8 kg/m2. Our quantified reference values for psoas cross -sectional area (CSA) index at L3 level (males/females respectively) were 6.3 ± 1.8 and 4.8 ± 1.9 cm2 /m2, and density was 46.1 ± 5 and 41 ± 5 HU at that level. Older age (standardized beta coefficient − 0.12, p = 0.04), sex (− 0.32, p < 0.001) and BMI (0.17, p = 0.002) were significantly associated with CSA index of psoas at L3. Density, however, was associated with triglycerides level (− 0.21, p < 0.001), in addition to age (− 0.22, p < 0.0001), sex (− 0.27, p < 0.001) and BMI (− 0.1, p = 0.05). Our study validates the normative values of psoas muscle mass and density in healthy individuals and suggests correlations with clinical parameters. We demonstrate the significance of measuring not only the mass of the muscle, but also its density, as it has a valid association with metabolic parameters, including BMI and lipid level, even in healthy individuals and in the normal range of the tests. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a common condition in women with breast cancer, however still presents limitations for an effective diagnosis. This study aimed to evaluate the agreement and diagnostic accuracy of an anthropometric equation in diagnosing sarcopenia in women with breast cancer based on different constructs. Methods: Cross-sectional study carried out with women with breast cancer aged ≥ 20 years. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was obtained by the handgrip strength test (HGS) and muscle mass (MM) by dual-energy x-ray absorptiometry (DXA) and by the anthropometric predictive equation. For the diagnosis of sarcopenia, eight constructs were proposed based on the MM assessment method (equation or DXA) and different cutoff points. Agreement analyses using Cohen's Kappa test and diagnostic performance measures were performed. The significance level for all tests was 5%. Results: A total of 122 women, with a mean age of 55.3 ± 11.4 years, were evaluated. There was a predominance of brown participants (50.8%), insufficiently active (57.4%), with diagnosis time ≤ 3 months (54.1%), and with invasive breast carcinoma (69.7%). The prevalence of sarcopenia ranged from 3.3 to 8.2%, depending on the construct used. The constructs determined from the cutoff points < 16.0 kg/< 7.58 m² and < 23.0 kg/< 7.58 m² were the ones that showed the best ability to detect sarcopenia. Conclusion: The anthropometric equation showed sufficient diagnostic capacity to be used as an alternative in identifying sarcopenia in women with breast cancer. [ABSTRACT FROM AUTHOR]

Aim: Patients with osteoporosis who also have sarcopenia are at a high risk for falls and fractures. Early detection of sarcopenia is crucial for these patients. This study aimed to compare the effectiveness of SARC-F, SARC-CalF, and calf circumference (CC) as screening tools for sarcopenia in patients with osteoporosis. Methods: This cross-sectional study was retrospectively conducted on patients who attended the outpatient clinic for Osteoporosis and Sarcopenia at Kyoto Medical Center. Sarcopenia was determined based on low skeletal muscle mass and weak handgrip strength. Sensitivity and specificity analyses were conducted on SARC-F, SARC-CalF, and CC. The diagnostic utility of these three tools was compared using the receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results: A total of 225 patients (men/women: 33/192) with a median age of 69.0 years (interquartile range: 61.0‒75.0) were enrolled. The prevalence of sarcopenia was found to be 11.6%. CC had the highest sensitivity (80.8%), while SARC-F had the highest specificity (93.0%) for detecting sarcopenia. ROC analysis revealed that all three tools had significant potential for sarcopenia diagnosis, with SARC-CalF having the highest AUC compared to SARC-F and CC (0.753 vs. 0.619 and 0.700). A multivariate logistic regression, incorporating other confounders as explanatory variables, revealed that SARC-CalF was independently related to sarcopenia (odds ratio: 14.80, 95% confidence interval: 3.83–57.30, p < 0.001). Conclusion: In patients with osteoporosis, SARC-CalF is more effective in the early detection of sarcopenia than SARC-F and CC. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) knee is one of the most common chronic degenerative conditions that imposes clinical and economic burdens on individuals and societies worldwide. Previous studies showed vitamin D levels correlated positively with lean muscle mass and grip strength, implying that vitamin D supplementation may improve muscle health in knee OA subjects. This randomized controlled trial (RCT) aims to compare the effects of vitamin D supplementation on knee muscle strength, physical function, pain, and sarcopenia status in patients with end-stage knee OA. Patients and outcome assessors will be blinded to group allocation. Fifty-six end-stage knee OA patients with vitamin D insufficiency fulfilling our inclusion criteria will be invited to participate in this study. Patients will be randomly assigned to take vitamin D supplementation (4,000 IU capsule daily) or placebo for six months. Measurements will be taken at baseline, three and six-month after the commencement of the vitamin D supplement, and 6-month after the interventional period. The primary outcome includes the isometric quadriceps and hamstring muscle strength measured by a hand-held dynamometer. Secondary outcomes include pain, performance-based and self-reported physical function and sarcopenia status. The success of this study will provide scientific evidence of whether the relatively cheap and well-tolerated vitamin D supplement can improve quadriceps muscle strength, physical function, pain symptoms, and sarcopenia status of this increasingly large population for end-stage knee OA patients. The study has great clinical significance given Hong Kong's lengthy and growing waiting list for complete knee replacement procedures. Trial registration: The trial was registered on clinicaltrials.gov (NCT05981534) on 31st July 2023. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, characterized by the loss of skeletal muscle, is assessed using appendicular skeletal muscle mass indices (ASMI). Various international groups propose different ASMI thresholds for assessing sarcopenia. However, the optimal ASMI that correlates best with physical performance measures in older Turkish adults remains unexplored. This study aims to determine which ASMI is most closely associated with physical performance measures, particularly low handgrip strength (dynapenia), in Turkish older adults. Methods: The study included 326 individuals aged 60 and above. Comprehensive geriatric assessments were conducted on all participants, along with anthropometric evaluations and body composition analyses. ASMI was calculated by adjusting height squared, weight, and body mass index (BMI). Physical performance was assessed through handgrip strength, gait speed, and the chair stand test. Results: The mean age of the participants was 74 ± 5.77 years, with 59.8% being women and 37.5% having dynapenia. Height-squared adjusted ASMI was not significantly associated with gait speed or the chair stand test. Weight-adjusted ASMI correlated with handgrip strength and gait speed but not with the chair stand test. Both height and weight-adjusted ASMI did not differ significantly between participants with and without dynapenia (p > 0.05). BMI-adjusted ASMI significantly correlated with all physical performance parameters (p < 0.05). Furthermore, in multivariate regression analysis, BMI-adjusted ASMI (OR = 0.028, 95% CI = 0.01–0.31, p = 0.006) was independently associated with dynapenia. Conclusion: The study indicates that ASMI adjusted for BMI shows stronger correlations with all physical performance parameters and is independently associated with dynapenia. Utilizing ASMI adjusted for BMI may improve sarcopenia diagnosis in Turkish older adults. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a geriatric disease characterized by loss of muscle mass and strength. Although combined exercise and nutrition intervention are known to be effective for sarcopenia, clinical trials involving outpatients with sarcopenia in primary care are scarce. We describe a protocol for a trial to examine the effects of a 12-week combined exercise and nutrition intervention in Korean older adults with possible sarcopenia in community-based primary care. Methods: This multicenter, randomized, controlled trial will include 94 community-dwelling older outpatients aged 65–85 years with possible sarcopenia (47 participants in the intervention and control groups each). Resistance exercises, which incorporate concentric and eccentric exercises, will consist of an introductory phase (3 weeks: twice-weekly supervised exercise sessions and once-weekly home exercises; contraction exercises), an expanded phase (3 weeks: twice-weekly supervised exercise sessions and once-weekly home exercises; eccentric exercises), and a maintenance phase (6 weeks: once-weekly supervised exercise sessions and twice-weekly home exercises; power/eccentric exercises). Nutritional supplementation will be provided according to the nutritional status of the participants using a Mini-Nutritional Assessment. Participants will be assessed at baseline, 12 and 24 weeks, and the primary outcome will be the 5-times chair stand test results. Discussion: To the best of our knowledge, this will be the first clinical trial to evaluate the efficacy of a combined exercise and nutritional supplementation intervention in older outpatients with possible sarcopenia in community-based primary care clinics. These findings will provide new insights to clinicians regarding the long-term usability for doctors and outpatients with possible sarcopenia in community-based primary care. Trial registration: This trial was prospectively registered at ClinicalTrials.gov on September 16, 2023 (registration number: NCT06049914). [ABSTRACT FROM AUTHOR]

Background: Adults with cerebral palsy (CP) have a high risk of cardiometabolic diseases. It is unknown whether this risk is elevated in young people with CP and whether exercise can reduce this risk. Therefore, we investigated the effects of the EXErcise for Cerebral Palsy (EXECP) intervention on cardiometabolic risk in children and young adults with CP and compared this risk to typically developing children and young adults (TDs). Methods: Ambulatory male and female participants with spastic CP, aged 9–24 years, and age- and sex-matched TDs without musculoskeletal disorders were recruited. Participants with CP were measured at baseline, after a three-month control period manifesting normal development, and after the three-month strength, gait, and flexibility training intervention. TDs were measured at baseline and after the control period. They did not attend the intervention. Cardiometabolic risk factors included body weight, body fat percentage, and skeletal muscle mass index assessed with bioimpedance; resting systolic and diastolic blood pressure and aortic pulse wave velocity assessed with a non-invasive oscillometric device; fasting plasma high-density and low-density lipoprotein cholesterol, triglyceride, and glucose levels. Data were analyzed with independent samples t-tests and linear mixed-effects models adjusted for sex and age. Results: The study involved 18 participants with CP (13 males, 9–22 year, mean 14.2 ± 4.4) and 17 TDs (12 males, 9–22 year, mean 14.6 ± 4.3). At baseline, participants with CP had a 1.0 (95% confidence interval (CI) [-2.0, -0.0]) kg/m2 lower skeletal muscle mass index than TDs. During the control period, no statistically significant between-group differences were observed in the change of any outcome. In the CP group, body weight (β = 1.87, 95% CI [1.04, 2.70]), fat percentage (β = 1.22 [0.07, 2.37], and blood glucose (β = 0.19, 95% CI [0.01, 0.37]) increased, while diastolic blood pressure (β=-2.31, 95% CI [-4.55, -0.06]) and pulse wave velocity (β=-0.44, 95% CI [-0.73, -0.16]) decreased. In the TD group, only body weight increased (β = 0.85, 95% CI [0.01, 1.68]) statistically significantly. In the CP group, no changes were observed during the intervention. Conclusions: Young people with and without CP do not exhibit significant differences in most cardiometabolic risk factors. EXECP intervention may attenuate some adverse development trajectories occurring without the intervention but greater volume and intensity of aerobic exercise may be needed to reduce cardiometabolic risk. Trial registration: ISRCTN69044459; Registration date 21/04/2017. [ABSTRACT FROM AUTHOR]

Background: Individuals with class II/III obesity have a high percentage of body fat. Assessing body composition in cases of severe obesity can be difficult and controversial both in clinical practice and scientific research. Thus, it is essential to explore the different aspects of evaluating body composition and to discuss the available methods to assess it in this population. Aims: To summarise and discuss the methods used to measure body composition in adults with class II/III obesity and their potential in clinical practice and scientific research. Methods: This is a narrative review using data from PubMed, Scielo, and Lilacs databases. Original articles on body composition analysis in adults with class II/III obesity i.e., a BMI ≥ 35 kg/m2 were eligible. Body composition assessment methods were analysed and described. Results: Some imaging methods produced significantly accurate results. Dual-energy X-ray absorptiometry (DXA) significantly produces accurate results and has been used in clinical studies. However, due to its high cost, it is not applicable in clinical practice. Multifrequency bioelectrical impedance analysis (BIA) has good accuracy and is more appropriate for clinical practice than other methods. We have highlighted several aspects of the importance and applicability of performing body composition analysis in individuals with class II/III obesity. Conclusion: DXA has been considered the most adequate method for clinical research. Multifrequency BIA may be a viable alternative to DXA for use in clinical practice. Assessing body composition and its components is important for people with class II/III obesity. It can help improve the effectiveness of interventions and clinical treatments, especially in reducing the risk of losing muscle mass. Muscle loss can cause sarcopenic obesity and other clinical complications, so understanding body composition is crucial. Assessing body composition can also help understand the impact of interventions on bones and avoid clinical complications. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer, is a deadly cancer, often diagnosed late and resistant to current therapies. PDAC patients are frequently affected by cachexia characterized by muscle mass and strength loss (sarcopenia) contributing to patient frailty and poor therapeutic response. This study assesses the mechanisms underlying mitochondrial remodeling in the cachectic skeletal muscle, through an integrative exploration combining functional, morphological, and omics-based evaluation of gastrocnemius muscle from KIC genetically engineered mice developing autochthonous pancreatic tumor and cachexia. Cachectic PDAC KIC mice exhibit severe sarcopenia with loss of muscle mass and strength associated with reduced muscle fiber's size and induction of protein degradation processes. Mitochondria in PDAC atrophied muscles show reduced respiratory capacities and structural alterations, associated with deregulation of oxidative phosphorylation and mitochondrial dynamics pathways. Beyond the metabolic pathways known to be altered in sarcopenic muscle (carbohydrates, proteins, and redox), lipid and nucleic acid metabolisms are also affected. Although the number of mitochondria per cell is not altered, mitochondrial mass shows a twofold decrease and the mitochondrial DNA threefold, suggesting a defect in mitochondrial genome homeostasis. In conclusion, this work provides a framework to guide toward the most relevant targets in the clinic to limit PDAC-induced cachexia. [ABSTRACT FROM AUTHOR]

Background/Objectives: Body composition (BC) affects the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN). Currently, dual-energy X-ray absorptiometry (DEXA) is considered the gold standard for assessing BC, even though it has some limitations, including immobility, ionizing radiation, and patient weight restrictions. The aim of the study was to evaluate the correlations of BC parameters measured by bioelectrical impedance analysis (BIA) with those measured by DEXA in patients with MASLD and HTN. Methods: Overall, 78 patients with MASLD and HTN underwent the following study procedures: compilation of an anamnesis, physical examination of a patient, laboratory tests, abdominal ultrasound, BIA, DEXA, and anthropometric measurements. Results: The agreement between BIA and DEXA in diagnosing reduced skeletal muscle mass (SMM) in patients with MASLD and HTN was moderate (kappa values were 0.440 and 0.404 in males and females, respectively). Significant strong direct correlations were found between fat mass (FM) and body fat percentage measured by BIA with corresponding measurements by DEXA (p < 0.001 for both). The area under the receiver operating characteristic curves (AUC) of SMM to body weight ratios calculated using BIA data were 0.834 and 0.929 for reduced appendicular SMM determined by DEXA in males and females with MASLD and HTN, respectively. Conclusions: In conclusion, BIA is an easy-to-use and widely available tool for assessing SMM and FM in patients with MASLD and HTN, demonstrating reliable agreement with DEXA measurement results and completely free of its limitations. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, characterized by the loss of skeletal muscle mass, is an emerging comorbidity associated with poor outcomes in cardiovascular surgery. Its impact on mortality in patients undergoing valve surgery for infective endocarditis (IE) remains underexplored. This study investigates the relationship between sarcopenia, measured by the Psoas muscle area index (PMAi), and mortality in patients with IE undergoing valve surgery. Materials and Methods: We retrospectively analyzed 68 patients with IE who underwent valve surgery at a tertiary care center from 2013 to 2021. Sarcopenia was defined as being in the lowest quartile of PMAi, measured via preoperative computed tomography (CT). Baseline characteristics, survival outcomes, and factors influencing mortality were analyzed using Kaplan–Meier survival curves and Cox proportional hazards regression. The predictive value of PMAi for 1-year and 3-year mortality was assessed via receiver operating characteristic (ROC) curves. Results: Sarcopenia was strongly associated with increased mortality at both 1-year (HR: 0.378, p = 0.010) and 3-year follow-ups (HR: 0.457, p = 0.012). Female sex (OR: 275.748, p < 0.001) and older age (OR: 9.995, p = 0.003) were significant predictors of sarcopenia. Chronic kidney insufficiency (CKI) and the use of heart failure medication therapy also significantly impacted survival outcomes. Conclusions: Sarcopenia is a strong independent predictor of short- and mid-term mortality in patients undergoing valve surgery for IE. Routine radiological assessment of sarcopenia using PMAi could improve risk stratification and guide preoperative interventions. Tailored management strategies, especially in older women and patients with CKI, may enhance outcomes in this high-risk population. [ABSTRACT FROM AUTHOR]

In individuals with a spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre- and post-intervention. The results suggest a potential preservation of muscle CSA in the Comb-NMES group compared to a control group. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI may attenuate inflammatory pathways linked to muscle atrophy and promote muscle repair. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population. [ABSTRACT FROM AUTHOR]

As we age, we lose muscle strength and power, a condition commonly referred to as sarcopenia (ICD-10-CM code (M62.84)). The prevalence of sarcopenia is about 5–10% of the elderly population, resulting in varying degrees of disability. In this review we emphasise that sarcopenia does not occur suddenly. It is an aging-induced deterioration that occurs over time and is only recognised as a disease when it manifests clinically in the 6th–7th decade of life. Evidence from animal studies, elite athletes and longitudinal population studies all confirms that the underlying process has been ongoing for decades once sarcopenia has manifested. We present hypotheses about the mechanism(s) underlying this process and their supporting evidence. We briefly review various proposals to impede sarcopenia, including cell therapy, reducing senescent cells and their secretome, utilising targets revealed by the skeletal muscle secretome, and muscle innervation. We conclude that although there are potential candidates and ongoing preclinical and clinical trials with drug treatments, the only evidence-based intervention today for humans is exercise. We present different exercise programmes and discuss to what extent the interindividual susceptibility to developing sarcopenia is due to our genetic predisposition or lifestyle factors. [ABSTRACT FROM AUTHOR]

Data in terms of how active vitamin D supplementation affects muscle mass and function in end-stage renal disease (ESRD) patients has led to inconclusive results. The main goal of this research was to examine the association of active vitamin D supplementation and risk of the deterioration of muscle mass and function among ESRD patients on peritoneal dialysis (PD). Eligible ESRD patients on PD were prospectively included, and followed up at 3-month intervals in the tertiary care center. Based on the medications during the 12-month follow-up period, the patients were divided into two groups (vitamin D users and non-users). The deterioration of muscle mass and function was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 (AWGS 2019). Primary outcome was defined as the deterioration of muscle mass and function at the end of the 12-month follow-up. The absolute diffecence and 95% confidence interval (CI) of the incidence of deterioration between vitamin D users and non-users was estimated. The association of vitamin D supplementation with risk of the deterioration of muscle mass and function during the 12-month follow-up period, was examined by employing multivariate logistic regression models. A total of 229 incident PD patients (6 of whom were lost in follow-up) were included. During the entire study period, 54.7% (122/223) of the remaining patients were considered users of oral active vitamin D. The incidence of deterioration in muscle mass and function was 30.5% (68/223) throughout the entire follow-up. In this regard, the rate was 23.0% (28/122) that received oral active vitamin D, while it was 39.6% (40/101) in the group that did not receive it, with an absolute diffecence of -16.6% (95% CI − 4.5, − 28.7) and an estimated relative risk (RR) of 0.784 (95% CI 0.651–0.943). After adjustment for potential confounding factors in logistic regression model, vitamin D users group was still associated with decreased risk of the deterioration of muscle mass and function (OR 0.330, 95% CI 0.159–0.683, P = 0.003). In secondary analysis, the relationship between oral active vitamin D and the deterioration of muscle mass and function remained consistent (≤ 0.25 µg per day vs. non-users; OR 0.300, 95% CI 0.131–0.688, P = 0.004); however, no significant relationship was identified in patients receiving a mean daily dose of > 0.25 µg compared with non-users (OR 0.389, 95% CI 0.146–1.034, P = 0.058). These results indicate that active vitamin D supplementation was significantly associated with a decreased risk of the deterioration of muscle mass and function in incident PD patients with ESRD. However, the amount and type of vitamin D used and the duration of the intervention warrant further randomized controlled trials to confirm the possibility that such medication improves sarcopenia in ESRD patients. [ABSTRACT FROM AUTHOR]

Background and objective: The global aging population has led to increased noncommunicable diseases, often linked to poor diet and declining muscle strength and mass. This study assessed leucine intake and sarcopenia indicators among 181 adults aged 60–80 in Santiago, Chile, participating in the Program for Complementary Food in Older People (PACAM), with 80% being women. Methods: Sarcopenia was evaluated through muscle strength and mass using the EWGSOP2 criteria for its identification. Results: 78.45% of participants did not meet the recommended leucine intake of 3 g per day and sarcopenia was identified in 17.13% of them. The skeletal muscle index was 48.07%, and hand grip strength was 26.52%, with men showing significantly higher grip strength (48.60% vs. 28.80%, p = 0.00). Inadequate leucine intake was more common in those aged 60–75 (85.9%) than those over 75 (p = 0.03). No significant differences in BMI, grip strength, or muscle mass were found between those with adequate and inadequate leucine intake, and PACAM food consumption did not significantly affect these parameters. A sub-analysis showed significant differences in grip strength among powdered dairy drink consumers (35.20% vs. 17.80%, p = 0.01). Conclusions: Chilean elderly participating in PACAM present a high prevalence of sarcopenia and leucine deficiency among with no notable benefits from PACAM foods intake. Despite the limitations of the local body composition assessment method, this research addresses a critical public health issue in Chile. Future studies should evaluate physical performance and focus on leucine supplementation to clarify its effects on sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage. Methods: We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88). Results: Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice. Conclusions: Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer. [ABSTRACT FROM AUTHOR]