Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.

OBJECTIVE: To determine the influence of serum sodium on physical, psychologic and sexual function. METHODS: This is a cross-sectional survey on 3340 community-dwelling men aged 40-79 years from a prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia ([Na+]G) was used. RESULTS: The relationship between [Na+]G and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for [Na+]G in either the lowest or the highest ends of the range. After dividing the sample into [Na+]G < 136 mmol/L (n = 81), 136-147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and [Na+]G, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum [Na+]G > 147 mmol/L (B = 0.15 [0.04;0.26], p < 0.01) but no relationship with [Na+]G < 136 mmol/L. Likewise, the relationship of [Na+]G with concerns about sexual dysfunction was confirmed only for men with serum [Na+]G > 147 mmol/L. CONCLUSIONS: This is the first study supporting an association between [Na+]G and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of [Na+]G, independently of other relevant factors.

Fate and removal of antimony in response to stringent control activities after a mine tailing spill.

When tailing spill accidents occur, the risk of contamination by antimony (Sb) tailings into adjacent rivers, sediments, aquifers and soil environments is high. The Sb concentrations in water and sediment under different stringent control activities were investigated for 60 days in the Jialing River basin after a tailing spill accident. Both reservoir regulation and the construction of a temporary dam with coagulation dosing remarkably reduced the Sb levels in the river water. The increase in dissolved Sb caused by the spill was reduced from ~400 µg/L in the inflow to ~200 µg/L in the outflow by reservoir regulation. Moreover, reservoir regulation led to a high concentration of Sb in the reservoir sediment, which was difficult to remove and may cause subsequent unpredictable long-term ecological and health risks. In contrast, the Sb-enriched deposition inside the temporary dam was convenient to remove. Notably, temperature alternations between day and night in winter resulted in a large fluctuation in coagulation efficiency, which may cause the failure of stringent control projects. The results of this study suggest potential improvements to stringent control activities after mine tailing accidents to mitigate environmental impacts and prevent secondary risks.

Acute Toxicity and Hazardous Concentrations of Zinc to Native Freshwater Organisms Under Different pH Values in China.

Zinc bioavailability to aquatic organisms varies greatly under different pH values. In the present study, five native species in China and four common international test species were selected to investigate the influence of changing pH on acute zinc toxicity. The results showed that the higher trophic levels exhibited increasing sensitivity to zinc as pH decreased. However, when the pH value was between 8 and 11, the acute toxicity of zinc was relatively constant. In addition, by using a species-sensitivity distribution (SSD) method, the short-term hazardous concentrations of zinc at different pH values (based on the 5th percentiles of the pH-specific SSDs) were determined to be 17.26 µg/L (pH 4), 48.31 µg/L (pH 5), 80.34 µg/L (pH 6) and 230.6 µg/L (pH 7), respectively. The present study provides useful information for deriving water quality criteria and assessing the risks of metals in the near future.

Analysis of first-episode and chronic schizophrenia using multi-modal magnetic resonance imaging.

OBJECTIVE: The brain structure and function differences among first-episode schizophrenia (FESZ) patients, chronic schizophrenia (CSZ) patients, and normal control (NC) subjects were investigated using structural and functional magnetic resonance imaging (MRI). Also, a support vector machine (SVM) combined with recursive feature elimination (RFE) was used for classification. PATIENTS AND METHODS: First, 44 FESZ patients, 44 CSZ patients, and 56 NC subjects were recruited, and structural MRI images were acquired. The regional gray matter volumes (GMVs) of 90 regions of interest (ROIs) were calculated, two-sample t-tests were conducted to analyze the GMV differences among the groups, and the partial correlations between the Positive and Negative Syndrome Scale (PANSS) scores and altered regional GMVs were calculated. Individual functional MRI images of the three groups were measured. The individual regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and degree of centrality (DC) values of the 90 ROIs were calculated and used to evaluate the differences among the groups. Then, the partial correlations between the PANSS scores and altered regional ReHo, ALFF, and DC were determined. An SVM combined with RFE was employed for classification using both structural and functional MRI input features. The sensitivity and specificity were measured to quantify the SVM performance. RESULTS: The GMVs in the bilateral calcarine of FESZ and CSZ patients were significantly lower than that of NC subjects. Compared to the NC group, the GMV was significantly reduced in numerous additional brain regions of the CSZ group. In comparison to the NC group, the patient groups exhibited significant ReHo increases in several regions and ReHo reductions in the occipital lobe. ReHo in the insula and left postcentral gyrus of CSZ patients were significantly lower than that of the NC subjects. Compared with the NC group, both patient groups exhibited ALFF aberrances in numerous regions. A significant reduction of ReHo, ALFF, and DC in certain regions were also found in patient groups compared with that of NC group. Significant positive correlations were found between the PANSS scores and ReHo and ALFF of the temporal and frontal lobes, while these correlations were negative in the occipital lobe. The SVM with RFE achieved excellent classification performance. The best performance was obtained using the following inputs: the ReHo and ALFF for FESZ/NC classification; the DC, ReHo, and ALFF for FESZ/CSZ classification; and the ReHo and ALFF for CSZ/NC classification. CONCLUSIONS: Our data indicate that compared with the FESZ patients, brain GMV aberrances was increased in the CSZ patients. The functional features including DC, ReHo, and ALFF, could facilitate FESZ diagnosis, which is more sensitive than structural features in classification. The SVM with RFE presents excellent classification performance and assists SZ diagnosis.

Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (ß-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

Genome-wide analysis of the maize (Zea may L.) CPP-like gene family and expression profiling under abiotic stress.

Cysteine-rich polycomb-like (CPP) proteins are members of a small family of transcription factors, which have been identified and characterized in Arabidopsis, rice, and soybean. In this study, we investigated CPP-like genes in the maize genome. The results revealed 13 putative CPP-like genes, which were found to encode 17 distinct transcripts and were distributed unequally on 7 of 10 maize chromosomes. Analysis of phylogenetic relationships showed that Arabidopsis, rice, and maize CPP-like transcription factors can be grouped into two subfamilies. We also used real-time RT-PCR to evaluate changes in the transcript levels of ZmCPP genes in response to abiotic stresses (heat, cold, salt, and drought stresses). These findings provide an overview of the evolution of the ZmCPP gene family, which will aid in the functional characterization of CPP-like genes in maize growth and development.

Correlation analysis of genetic diversity and population structure of Houttuynia cordata Thunb with regard to environment.

To study the levels of genetic diversity, and population structure, of Houttuynia cordata Thunb, the genetic background and relationships of populations were analyzed in terms of environmental factors. The genetic diversity and population structure of H. cordata were investigated using sequence-related amplified polymorphisms and correlation with environmental factors was analyzed using the SPSS software. Two thousand one hundred sixty-three sites were amplified from 41 pairs of primers, 1825 of which were polymorphic, and the percentage of polymorphic loci was 84.37%; the percentage of polymorphic sites was 72.14 and 67.77% at the species and population level, respectively. The observed number of alleles was 1.52 and 1.30 at species and population level, respectively. The effective number of alleles was 1.38 and 1.24 at species and population level, respectively. The Nei's diversity was 0.26 and 0.15 at species and population level, respectively. The Shannon's information index was 0.87 and 0.63 at species and population level, respectively. The genetic differentiation coefficient of populations was 0.51, and 12 populations were divided into three classes based on D = 0.20; the genetic diversities of different populations are correlated at different significance levels (P < 0.05) with environmental factors. Genetic differentiation existed among populations and the populations exhibited heteroplasmy.

Ethnic differences in bone geometry between White, Black and South Asian men in the UK.

Relatively little is known about the bone health of ethnic groups within the UK and data are largely restricted to women. The aim of this study was to investigate ethnic differences in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), bone geometry and strength in UK men. White European, Black Afro-Caribbean and South Asian men aged over 40years were recruited from Greater Manchester, UK. aBMD at the spine, hip, femoral neck and whole body were measured by DXA. Bone geometry, strength and vBMD were measured at the radius and tibia using pQCT at the metaphysis (4%) and diaphysis (50% radius; 38% tibia) sites. Adjustments were made for age, weight and height. Black men had higher aBMD at the whole body, total hip and femoral neck compared to White and South Asian men independent of body size adjustments, with no differences between the latter two groups. White men had longer hip axis lengths than both Black and South Asian men. There were fewer differences in vBMD but White men had significantly lower cortical vBMD at the tibial diaphysis than Black and South Asian men (p<0.001). At the tibia and radius diaphysis, Black men had larger bones with thicker cortices and greater bending strength than the other groups. There were fewer differences between White and South Asian men. At the metaphysis, South Asian men had smaller bones (p=0.02) and lower trabecular vBMD at the tibia (p=0.003). At the diaphysis, after size-correction, South Asian men had similar sized bones but thinner cortices than White men; measures of strength were not broadly reduced in the South Asian men. Combining pQCT and DXA measurements has given insight into differences in bone phenotype in men from different ethnic backgrounds. Understanding such differences is important in understanding the aetiology of male osteoporosis.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower ß C-terminal cross-linked telopeptide (ß-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and ß-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and ß-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

Ratiometric detection of oligonucleotide stoichiometry on multifunctional gold nanoparticles by whispering gallery mode biosensing.

A label-free method is developed to ratiometrically determine the stoichiometry of oligonucleotides attached to the surface of gold nanoparticle (GNP) by whispering gallery mode biosensing. Utilizing this scheme, it is furthermore shown that the stoichiometric ratio of GNP attached oligonucleotide species can be controlled by varying the concentration ratio of thiolated oligonucleotides that are used to modify the GNP.

Associations of obesity with socioeconomic and lifestyle factors in middle-aged and elderly men: European Male Aging Study (EMAS).

BACKGROUND: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently. OBJECTIVE: In this study, we examined the associations of socioeconomic status (SES) and lifestyle factors with BMI and waist circumference (WC) in middle-aged and elderly European men. DESIGN AND SETTING: A cross-sectional study of 3319 men aged 40-79 years recruited from eight European centres. OUTCOMES: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles. RESULTS: The prevalence of BMI ≥ 30 kg/m(2) or WC ≥ 102 cm rose linearly with age, except in the eighth decade when high BMI, but not high WC, declined. Among men aged 40-59 years, compared with non-smokers or most active men, centre and BMI-adjusted RRRs for having a WC between 94 and 101.9 cm increased by 1.6-fold in current smokers, 2.7-fold in least active men and maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC ≥ 102 cm, notably 8.4-fold greater in least active men who smoked. Compared with men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65 years group and by 1.3-fold in the 40-75 years group. These relationships were weaker among elderly men. CONCLUSION: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age.

Expanding the genetic code for site-specific labelling of tobacco mosaic virus coat protein and building biotin-functionalized virus-like particles.

A method for site-specific and high yield modification of tobacco mosaic virus coat protein (TMVCP) utilizing a genetic code expanding technology and copper free cycloaddition reaction has been established, and biotin-functionalized virus-like particles were built by the self-assembly of the protein monomers.

Late-onset hypogonadism and mortality in aging men.

CONTEXT: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. OBJECTIVE: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. DESIGN, SETTING, AND PARTICIPANTS: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40-79 years in eight European countries was used for this study. MAIN OUTCOME MEASURE(S): All-cause, cardiovascular, and cancer-related mortality was measured. RESULTS: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. CONCLUSIONS: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying.

Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females.

BACKGROUND: Salivary testosterone (Sal-T) may be a useful surrogate of serum free testosterone. The study aims were to use a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to determine whether Sal-T concentrations accurately reflect Sal-T concentrations in both sexes and to investigate practical aspects of sample collection. METHODS: Saliva and serum samples were collected in 104 male and 91 female subjects. A more sensitive LC-MS/MS assay was developed to enable Sal-T quantitation in the low concentrations found in females. Saliva (200 µL) was extracted with 1 mL of methyl-tert-butyl ether following the addition of D5-testosterone. Quantitation was performed using a Waters TQ-S mass spectrometer. RESULTS: The assay achieved a lower limit of quantification of 5 pmol/L, sufficiently sensitive to measure testosterone in female saliva. Sal-T showed a diurnal variation but samples taken at weekly and monthly intervals showed no significant differences. Sal-T was stable at ambient temperature for up to 5 days, after freeze-thawing and 3 years frozen storage. Reference intervals for Sal-T were 93-378 pmol/L in males and 5-46 pmol/L in females. Sal-T correlated significantly with serum calculated free-T in males (r = 0.71, P < 0.001) and in females (r = 0.39, P < 0.001). CONCLUSIONS: These results confirm that testosterone can be reliably and accurately measured by LC-MS/MS in both adult male and female saliva samples. These results lay the foundation for further exploration of the clinical application of Sal- T as a reliable alternative to serum testosterone in the diagnosis and management of androgen disorders and assessment of androgen status in clinical research.

Obesity and weight management in the elderly: a focus on men.

The rising rate of overweight/obesity among the ever-growing ageing population is imposing massive and rapidly changing burdens of ill health. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults, mainly through its reduced impact on coronary heart disease, has often been misinterpreted that obesity is not as harmful in the elderly, who suffer a large range of disabling consequences of obesity. All medical consequences of obesity are multi-factorial and most alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. But severe obesity, e.g. BMI >40 may demand greater weight loss e.g. >15 kg to reverse type 2 diabetes. Since relatively reduced physical activity and reduced muscle mass (sarcopenic obesity) are common in the elderly, combining exercise and modest calorie restriction optimally reduces fat mass and preserves muscle mass - age presents no obstacle and reducing polypharmacy is a valuable outcome. The currently licensed drug orlistat has no age-related hazards and is effective in a low fat diet, but the risks from bariatric surgery begin to outweigh benefits above age 60. For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue liraglutide appears a safe way to promote and maintain substantial weight loss. Obesity and sarcopenia should be prevented from younger age and during life-transitions including retiral to improve future health outcomes and quality of life, with a focus on those in "obese families".

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study.

OBJECTIVE: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. DESIGN: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±S.D.) 4.4±0.3 years later. RESULTS: Paired testosterone results were available for 2395 men. Mean (±S.D.) annualised hormone changes were as follows: testosterone -0.1±0.95  nmol/l; free testosterone (FT) -3.83±16.8  pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5  nmol/l and LH 0.08±0.57  U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. CONCLUSIONS: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.

Investigating the role of pain-modulating pathway genes in musculoskeletal pain.

AIMS: The aim of this study was to determine if genetic variation in the pain-modulating gene DREAM and its pathway genes influence susceptibility to reporting musculoskeletal pain in the population. METHODS: Pairwise tag single nucleotide polymorphisms (SNPs) in DREAM, PDYN and OPRK1 were genotyped in a UK population-based discovery cohort in whom pain was assessed using blank body manikins at three time points. Depression and anxiety symptoms were assessed at the first time point. Zero-inflated negative binomial regression was used to test for association between SNPs and the maximum number of pain sites reported (0-29) across the three time points. Significantly associated SNPs (p < 0.05) were subsequently genotyped for validation in a cohort of European men with pain assessed at two time points. RESULTS: Thirty-five SNPs were genotyped in 1055 subjects, of whom 83% reported pain, in the discovery cohort. SNPs in each gene were associated with the maximum number of pain sites reported, were independent of symptoms of anxiety and depression and had a significant cumulative effect (p = 7.0 × 10(-5) ). Significantly associated SNPs were successfully genotyped in 1733 men, 76% of whom reported pain, in the validation cohort, but did not show significant association with the number of pain sites. CONCLUSIONS: Genetic variation in the DREAM pathway genes was associated with the extent of pain reporting in a population-based cohort. These findings were not replicated in a single independent cohort; however, given the potential of this pathway as a therapeutic target, further investigation in additional cohorts is warranted.

Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men.

UNLABELLED: The aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMD(a)) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMD(a) and were more likely to have osteoporosis compared with men without sarcopenia. INTRODUCTION: In men, the relationship between reduced muscle mass (sarcopenia) and BMD(a) is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men. METHODS: Men aged 40-79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD(a) were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m(2) plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD(a) and logistic regression to determine the association between sarcopenia and osteoporosis. RESULTS: Six hundred seventy-nine men with a mean age of 59.6 (SD = 10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD(a). Men with RASM at <7.26 kg/m² had significantly lower BMD(a) compared with those with RASM at ≥7.26 kg/m(2). In a multivariable model, aLM was most consistently associated with BMD(a). Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio = 3.0; 95 % CI = 1.6-5.8). CONCLUSIONS: Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.