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Loss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81–87/group), aged 55–74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738–0.845, p  < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.

Epidemiology of stunting in < 5 years old is well characterized; however, its prevalence in adolescence is inconsistent in different geographical locations. We estimated the prevalence of stunting in schoolgirls of Punjab, Pakistan, to standardize local references according to international and national references. In this population-wide cross-sectional study, 10,050 schoolgirls aged 8–16 years from 12 different districts of northern, central, and southern Punjab were analyzed. The prevalence of stunting was calculated by applying Centres for Disease Control and Prevention (CDC) and World Health Organisation (WHO) height-for-age references and the local reference for the study population. We used Cohen’s kappa statistics to analyze the agreement of our data with reference values, and chi-square test was used as the test of trend. Marked overestimation of the prevalence of stunting was observed (22.72% and 17.49% according to CDC and WHO, respectively) in comparison to local reference (4.94%). According to CDC and WHO references, there was an increasing trend of prevalence of stunting with higher age; however, data was comparable across all the age groups when local references were applied. We recommend that the prevalence of stunting in school-age girls should be determined by applying local height references rather than international ones to plan health strategies and treatments in the local population.

Patients with Parkinson’s disease (PD) present with an advanced form of age-related muscle loss or sarcopenia. However, the search for a biomarker to accurately predict muscle loss in PD remains elusive. We evaluated the biomarkers of neuromuscular junction (NMJ) stability, including c-terminal agrin fragment-22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of muscle wasting and physical capacity in PD. Male, 63—78 years patients of PD, were investigated for physical capacity, handgrip strength (HGS), and circulating biomarkers at the diagnosis and follow-up during rehabilitation 6 months apart. Patients with PD presented with elevated CAF22 and reduced BDNF and GDNF levels, which were partially restored to normal levels with rehabilitation. All three biomarkers showed significant dynamic associations with HGS and indexes of sarcopenia. Logistic regression revealed that the combination of biomarkers levels into a cumulative risk score enhanced the diagnostic accuracy of sarcopenia. In brief, measurements of plasma BDNF, GDNF, and CAF22 may be helpful in timely diagnosis and/or evaluation of sarcopenia.

Background A sizable proportion of school-going children from developing countries has abnormal growth parameters, often not standardized with international reference values. We aimed to assess the prevalence of underweight, overweight, and obesity in the schoolgirls of Punjab according to international and local references. Methods In this population-based cross-sectional study, 10,050 school-going girls aged 8–16 years from 12 districts of northern, central, and southern Punjab were recruited. Estimates of normal weight, underweight, overweight and obesity were calculated in the girls according to three international BMI references including centers for disease control (CDC) 2000, the international obesity task force (IOTF) 2012 and world health organisation (WHO) 2007 in addition to a local reference for the population under study. We used Cohen’s kappa statistics to analyse the agreement of our data with reference values. Results There was marked overestimation of underweight (23.9%, 14.5%, 15.2% and 4.37%), slight underestimation of overweight (5.3%, 7.3%, 7.9% and 8.97%) and moderate underestimation of obesity (1.9%, 1.5%, 2.2% and 5.67%) according to CDC, IOTF, WHO and local reference, respectively. When the weight status of the study cohort was compared with the local data, we found comparable results in all four weight categories. Conclusion We recommend population-wide further studies to estimate the prevalence of weight status in school-age girls for devising appropriate references and for planning strategies for public health policy and management.

Background Child’s growth has been considered an important indicator to evaluate health trends in a population and to devise strategies accordingly. The purpose of the present study was to determine most commonly occurring weight abnormalities among school-going girls from Punjab and to compare with international growth references devised by World Health Organization (WHO) and Centre for Disease Control and Prevention (CDC). Methods In this cross-sectional study a sample of 10,050 child and adolescent girls from 12 districts, 35 public/private sector schools, located in rural, semi-urban and urban areas of northern, central and southern Punjab were included. Parameters were measured according to standardised techniques and centile curves obtained by Lambda, Mu, Sigma (LMS) method. Results The results showed an increase in weight, height and BMI of the Punjabi girls until 15 years. When compared with international growth references, weight and BMI in our population were significantly lowered; however, height was lower during 12–16 years of age and the differences observed were more pronounced with CDC as compared to WHO. When 3rd, 50th and 90th percentiles of weight, height and BMI in our population were compared with international standards, the values were lower in our paediatric population. Conclusion The Punjabi schoolgirls significantly differed from CDC and WHO references, and this difference should be taken into consideration for evaluation of growth abnormalities in our paediatric population. However, in the absence of national reference data, WHO standards have been considered more appropriate for comparison.

Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB (n = 83–101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.

Skeletal muscle dysfunction and reduced physical capacity are characteristic features of chronic obstructive pulmonary disease (COPD). However, the search for a reliable biomarker to assess muscle health in CODP remains elusive. We analyzed the course of hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in COPD in relation to spirometry decline and plasma extracellular heat shock protein-72 (eHSP72) and c-terminal fragment of agrin-22 (CAF22) levels. We evaluated male, 62–73 years old patients of COPD (N = 265) and healthy controls (N = 252) at baseline and after 12 and 24 months for plasma biomarkers, spirometry and HGS measurements. HGS declined significantly over time and plasma CAF22, but not eHSP72 levels, had a significant negative association with HGS and ASMI in COPD. Plasma CAF22 also had an association with walking speed and daily steps count in advanced COPD. Lower ASMI was associated with reduced HGS at all time-point. Narrow age-span of the study cohort and exclusion of lower-limb muscles from the analysis are limitations of this study. Taken together, we report that the plasma CAF22 may be a useful tool to assess muscle weakness and atrophy in COPD patients.

Muscle weakness is a risk factor for multiple diseases. However, most protocols to assess muscle weakness require clinical settings. A difficulty lifting 5 kg may be a simple measure of muscle weakness in domestic settings. However, no relevant study on assessing muscle weakness has been reported. We investigated the associations of difficulty lifting 5 kg with various musculoskeletal, cardiovascular, metabolic, and neurological diseases in geriatric adults aged 50 or above from 15 countries (n = 51,536) over five years. The data was collected by the Survey of Health, Ageing, and Retirement in Europe (SHARE) conducted between 2013 and 2020. Overall, 10,025 (19.5%) respondents exhibited difficulty lifting 5 kg at baseline in 2013. Over the next four years, these respondents exhibited higher risks for developing a low quality of life (QoL) (9.42%), depression (8.14%), low handgrip strength (7.38%), and osteoarthritis (6.98%) after adjusting for age and gender. Additionally, these respondents exhibited mild to moderate risks for developing rheumatoid arthritis, heart attack, diabetes mellitus, hypertension, Alzheimer’s disease, stroke, or hip fracture (all p < 0.05). After adjusting for age and country, the risks of developing various diseases were higher in men than in women. Collectively, difficulty lifting 5 kg can herald the onset of several cardiovascular, neurological, and musculoskeletal disorders along with a reduced QoL. We suggest that difficulty lifting 5 kg may be a valuable indicator of muscle weakness and poor health in domestic settings.

Clinical and experimental evidence point to the presence of considerable links between arthropathy, osteoarthritis (OA) in particular, and iron overload possibly due to oxidative stress and tissue damage. However, the specific cellular targets of iron overload-related oxidative stress in OA remain ambiguous . We examined the effects of iron overload on chondrocyte health using the C-20/A4 chondrocyte cell line. Cells were treated with increasing concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro . Treated cells were assessed for cell viability, cycling, apoptosis, collagen II synthesis, and oxidative stress along with cellular iron content and the expression of key iron regulatory genes. FAC treatment resulted in an increase in ferritin expression and a significant decrease in the expression of hepcidin, ferroportin, transferrin receptors 1 (TfR1) and TfR2. Increased labile iron content was also evident, especially in cells treated with high FAC at 24 h. High doses of FAC treatment also induced higher levels of reactive oxygen species, reduced collagen II production, disrupted cell cycle and higher cell death as compared with untreated controls. In conclusion, findings presented here demonstrate that iron overload disrupts cellular iron homeostasis, which compromises the functional integrity of chondrocytes and leads to oxidative stress and apoptosis.

Mechanical unloading of the body in the hindlimb unloaded (HU) mice induces pathology in multiple organs, but the effects on testes are poorly characterized. We investigated the histology and Raman spectroscopy of the mouse testes following HU condition. We divided male, c57BL/6j mice into ground-based controls or experimental groups for two and four weeks of HU. The testes tissues were dissected after euthanasia to investigate histological and Raman spectroscopic analysis. We found an HU-induced atrophy of testes irrespective of the time duration (p < 0.05). Histological analysis revealed that the HU induced epithelial thinning, luminal widening, and spermatozoa decline in the seminiferous tubules of the mouse testes. In addition, we found a thickening of the epididymal epithelia and tunica albuginea. These changes were accompanied by a generalized depression in the Raman spectra, indicating an altered concentration and/or orientation of several molecules. We also report reduced signal intensities of hydroxyproline and tryptophan, potentially contributing to testicular pathology during HU. Taken together, our findings indicate that the two or four weeks of HU induce disruption of testicular architecture and molecular phenotypes. Our results may have implications for understanding and/or treating male infertility associated with prolonged bed rest and spaceflight.