Bivariate genome-wide association study suggests that the DARC gene influences lean body mass and age at menarche

Lean body mass （LBM） and age at menarche （AAM） are two important complex traits for human health. The aim of this study was to identify pleiotropic genes for both traits using a powerful bivariate genome-wide association study （GWAS）. Two stud- ies, a discovery study and a replication study, were performed. In the discovery study, 909622 single nucleotide polymor- phisms （SNPs） were genotyped in 801 unrelated female Han Chinese subjects using the Affymetrix human genome-wide SNP array 6.0 platform. Then, a bivariate GWAS was performed to identify the SNPs that may be important for LBM and AAM. In the replication study, significant findings from the discovery study were validated in 1692 unrelated Caucasian female subjects One SNP rs3027009 that was bivafiately associated with left arm lean mass and AAM in the discovery samples （P=7.26x10-6） and in the replication samples （P=0.005） was identified. The SNP is located at the upstream of DARC （Duffy antigen receptor for chemokines） gene, suggesting that DARC may play an important role in regulating the metabolisms of both LBM and AAM.

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Prostate cancer （PCa） is the most common visceral malignancy in men with androgen deprivation therapy （ADT） the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data （up to 2 years） for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

New Mathematical Modelling on BMR and Weight Prediction for Ghanaians

Background: Basal Metabolic Rate (BMR) is the quantum of calories needed for optimum body function when at rest. This has long been an indicator of one’s health and the basis for determining the metabolic age of individuals. Many scholastic projects have led to the establishment of mathematical models and inventions that measure the BMR and other body composition parameters. However, existing computations have limitations as they do not offer accurate results for Ghanaians. Aim: The purpose of the study was to model BMR metrics that are most suitable for Ghanaians and to investigate the effect of caloric difference on weight, Lean Body Mass (LBM) and % fat composition that can be implemented with Information Technology. Research Methods and Procedures: This was an experimental study that adopted a quantitative approach. BMR and body composition were measured in a sample of 242 Ghanaian adults (141 males and 101 females) from 19 to 30 years of age. Body composition was measured using bioelectrical impendence analysis (BIA) in all participants. Each participant was under study for 7 days. A simple linear regression model was used to examine associations between BMR/calorie intake and total body weight and LBM. Results: There was a significant statistical relation between BMR and LBM and between BMR and weight of both men and women. Equations for BMR and weight were established for males and females. Furthermore, caloric intake differences affected changes in total weight as well as differences in % fat composition. Caloric intake however did not affect the difference in LBM. Conclusion: Caloric difference had an impact on total body weight and Lean Body Mass. The model derived from the study predicts weight change and BMR of Ghanaians from 19 to 30 years of age. It is termed the Health and Age Monitoring System (HAMS).

Prognostic role of sarcopenia in metastatic colorectal cancer patients during first-line chemotherapy:A retrospective study

BACKGROUND Sarcopenia is a condition characterized by decreased skeletal muscle mass due to physiological ageing or to a concomitant disease such as neoplasia.In cancer patients,a low lean body mass is suggested to be a negative prognostic factor for survival and for the development of dose-limiting chemotherapy toxicities irrespective of disease stage.AIM To evaluate the prognostic role of sarcopenia in patients with metastatic colorectal cancer(mCRC)undergoing first-line chemotherapy.METHODS Our retrospective analysis included 56 mCRC patients who received first-line chemotherapy from 2014 to 2017 at the Medical Oncology Unit of our hospital.Computerized scans were performed before starting chemotherapy and at the first disease reassessment.Sarcopenia was assessed using the skeletal mass index=muscle area in cm^(2)/(height in m^(2))calculated at the L3 vertebra.Overall survival and objective response rate were evaluated.Toxicities were analyzed during the first four cycles of therapy and graded according to Common Terminology Criteria for Adverse Events version 4.0.A loss of skeletal muscle mass≥5%was considered indicative of deterioration in muscle condition.RESULTS Median age was 67 years and 35.7%of patients were≥70 years old.Fourteen patients(25%)were sarcopenic at baseline computed tomography(CT)scan(7/33 men;7/23 women);5/14 sarcopenic patients were≥70 years old.Median followup was 26.8 mo(3.8-66.8 mo)and median overall survival was 27.2 mo(95%CI:23.3-37.3).Sarcopenia was not correlated to overall survival(P=0.362),to higher toxicities reported during the first 4 cycles of chemotherapy(P=1.0)or to response to treatment(P=0.221).At the first disease reassessment,a skeletal muscle loss(SML)≥5%was found in 17 patients(30.3%)3 of whom were already sarcopenic at baseline CT scan,while 7 patients became sarcopenic.SML was not correlated to overall survival(P=0.961).No statistically significant correlation was found between baseline sarcopenia and age(P=1.0),body mass index(P=0.728),stage at diagnosis(P=0.355)or neutrophil/lymphocyte ratio(P=0.751).CONCLUSION Neither baseline sarcopenia nor SML affected survival.In addition,baseline sarcopenia was not related to worse treatment toxicity.However,these results must be interpreted with caution due to the limited sample size.

Reproducibility of serial creatinine excretion measurements in peritoneal dialysis

AIMTo test whether muscle mass evaluated by creatinine excretion （EXCr） is maintained in patients with end-stage kidney disease （ESKD） treated by peritoneal dialysis （PD）, we evaluated repeated measurements of EXCr in a PD population.METHODSOne hundred and sixty-six PD patients （94 male, 72 female） receiving the same PD dose for the duration of the study （up to approximately 2.5 years） had repeated determinations of total （in urine plus spent dialysate） 24-h EXCr （EXCr T） to assess the adequacy of PD by creatinine clearance. All 166 patients had two EXCr T determinations, 84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements. EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times.RESULTSIn patients who were studied twice, with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EXCr T did not differ between the first and second study. In patients studied three times and whose fnal assessment occurred 24.7 ± 16.3 mo after initiating PD, EXCr T did not differ between the first and second study, but was significantly lower in the third study compared to the frst study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EXCr T did not differ between any of the studies. The average EXCr T value did not change signifcantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EXCr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more.CONCLUSIONThe average value of EXCr T remains relatively constantfor up to 2.5 years of follow-up in PD patients who adhereto the same PD schedule. However, repeated individualEXCr T values vary considerably in a large proportion ofthe patients. Further studies are needed to evaluatethe clinical signifcance of varying EXCr T values and thestability of EXCr T beyond 2.5 years of PD follow-up.

Plasma transthyretin is a nutritional biomarker in human morbidities

Transthyretin(TTR)is a small liver-secreted plasma protein that shows close correlations with changes in lean body mass(LBM)during the entire human lifespan and agglomerates the bulk of nitrogen(N)-containing substrates,hence constituting the cornerstone of body building.Amino acids(AAs)dietary restriction causes inhibition of TTR production and impairs the accretion of LBM reserves.Inflammatory disorders result in cytokine-induced abrogation of TTR synthesis and urinary leakage of nitrogenous catabolites.Taken together,the data indicate that malnutrition and inflammation may similarly suppress the production of TTR through distinct and unrelated pathophysiological mechanisms while operating in concert to downsize LBM stores.The hepatic synthesis of TTR integrates both machineries,acting as a marker of reduced LBM resources still available for defense and repair processes.TTR operates as a universal surrogate analyte that allows for the grading of residual LBM capacity to reflect disease burden.Measurement of TTR is a simple,rapid,and inexpensive micromethod that may be reproduced on a daily basis,hence ideally suited for the follow-up of the most intricated clinical situations and as a reliable predictor of any morbidity outcome.