Is exercise protective against influenza-associated mortality?

Background: Little is known about the effect of physical exercise on influenza-associated mortality. Methods and Findings: We collected information about exercise habits and other lifestyle, and socioeconomic and demographic status, the underlying cause of death of 24,656 adults (21% aged 30-64, 79% aged 65 or above who died in 1998 in Hong Kong, and the weekly proportion of specimens positive for influenza A (H3N1 and H1N1) and B isolation during the same period. We assessed the excess risks (ER) of influenza-associated mortality due to all-natural causes, cardiovascular diseases, or respiratory disease among different levels of exercise: never/seldom (less than once per month), low/moderate (once per month to three times per week), and frequent (four times or more per week) by Poisson regression. We also assessed the differences in ER between exercise groups by case-only logistic regression. For all the mortality outcomes under study in relation to each 10% increase in weekly proportion of specimens positive for influenza A+B, never/seldom exercise (as reference) was associated with 5.8% to 8.5% excess risks (ER) of mortality (P<0.0001), while low/moderate exercise was associated with ER which were 4.2% to 6.4% lower than those of the reference (P<0.001 for all-natural causes; P=0.001 for cardiovascular; and P=0.07 for respiratory mortality). Frequent exercise was not different from the reference (change in ER -0.8% to 1.7%, P=0.30 to 0.73). Conclusion: When compared with never or seldom exercise, exercising at low to moderate frequency is beneficial with lower influenza-associated mortality. © 2008 Wong et al.published_or_final_versio

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

published_or_final_versio

Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential

Recently adipose tissue has become a research topic also for the searching for an alternative stem cells source to use in cell based therapies such as tissue engineer. In fact Adipose Stem Cells (ASCs) exhibit an important differentiation potential for several cell lineages such as chondrogenic, osteogenic, myogenic, adipogenic and endothelial cells. ASCs populations isolated using standard methodologies (i.e., based on their adherence ability) are very heterogeneous but very few studies have analysed this aspect. Consequently, several questions are still pending, as for example, on what regard the existence/ or not of distinct ASCs subpopulations. The present study is originally aimed at isolating selected ASCs subpopulations, and to analyse their behaviour towards the heterogeneous population regarding the expression of stem cell markers and also regarding their osteogenic and chondrogenic differentiation potential. Human Adipose derived Stem Cells (hASCs) subpopulations were isolated using immunomagnetic beads coated with several different antibodies (CD29, CD44, CD49d, CD73, CD90, CD 105, Stro-1 and p75) and were characterized by Real Time RT-PCR in order to assess the expression of mesenchymal stem cells markers (CD44, CD73, Stro-1, CD105 and CD90) as well as known markers of the chondrogenic (Sox 9, Collagen II) and osteogenic lineage (Osteopontin, Osteocalcin). The obtained results underline the complexity of the ASCs population demonstrating that it is composed of several subpopulations, which express different levels of ASCs markers and exhibit distinctive differentiation potentials. Furthermore, the results obtained clearly evidence of the advantages of using selected populations in cell-based therapies, such as bone and cartilage regenerative medicine approaches.EU funded Marie Curie Actions Alea Jacta Est for a PhD fellowship. This work was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283)

Metabolic responses to high pCO2 conditions at a CO2 vent site in juveniles of a marine isopod species assemblage

We are starting to understand the relationship between metabolic rate responses and species' ability to respond to exposure to high pCO2. However, most of our knowledge has come from investigations of single species. The examination of metabolic responses of closely related species with differing distributions around natural elevated CO2 areas may be useful to inform our understanding of their adaptive significance. Furthermore, little is known about the physiological responses of marine invertebrate juveniles to high pCO2, despite the fact they are known to be sensitive to other stressors, often acting as bottlenecks for future species success. We conducted an in situ transplant experiment using juveniles of isopods found living inside and around a high pCO2 vent (Ischia, Italy): the CO2 'tolerant' Dynamene bifida and 'sensitive' Cymodoce truncata and Dynamene torelliae. This allowed us to test for any generality of the hypothesis that pCO2 sensitive marine invertebrates may be those that experience trade-offs between energy metabolism and cellular homoeostasis under high pCO2 conditions. Both sensitive species were able to maintain their energy metabolism under high pCO2 conditions, but in C. truncata this may occur at the expense of [carbonic anhydrase], confirming our hypothesis. By comparison, the tolerant D. bifida appeared metabolically well adapted to high pCO2, being able to upregulate ATP production without recourse to anaerobiosis. These isopods are important keystone species; however, given they differ in their metabolic responses to future pCO2, shifts in the structure of the marine ecosystems they inhabit may be expected under future ocean acidification conditions

Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p<0 center dot 0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2 center dot 60, 2 center dot 30-2 center dot 94) than in older individuals (aged 70-89 years: 2 center dot 01, 1 center dot 85-2 center dot 19; p=0 center dot 0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5 center dot 55, 4 center dot 15-7 center dot 44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0 center dot 05% (95% CI 0 center dot 03-0 center dot 07) per year in women compared with 0 center dot 08% (0 center dot 05-0 center dot 10) per year in men; the corresponding excess at ages 70-89 years was 1 center dot 08% (0 center dot 84-1 center dot 3 2) per year in women and 0 center dot 91% (0 center dot 77-1 center dot 05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained

Does sex matter in the associations between classic risk factors and fatal coronary heart disease in populations from the Asia-Pacific region?

Background: There is much interest in promoting healthy heart awareness among women. However, little is known about the reasons behind the lower rates of heart disease among women compared with men, and why this risk difference diminishes with age. Previous comparative studies have generally had insufficient numbers of women to quantify such differences reliably. Methods: We carried out an individual participant data meta-analysis of 39 cohort studies (32 from Asian countries and 7 from Australia and New Zealand). Cox models were used to estimate hazard ratios (HR) for coronary death, comparing men to women. Further adjustments were made for several proven coronary risk factors to quantify their contributions to the sex differential. Sex interactions were tested for the same risk factors. Results: During 4 million person-years of follow-up, there were 1989 (926 female) deaths from coronary heart disease (CHD). The age-adjusted and study-adjusted male/female HR (95% confidence interval [95% CI]) was 2.05 (1.89-2.22). At baseline, 54% of men vs. 7% of women were current smokers; hence, adjustment for smoking explained the largest component (20%) of this HR. A significant sex interaction was observed between systolic blood pressure (SBP) and CHD mortality such that a 10 mm Hg increase was associated with a 15% greater increase in the relative risk (RR) of coronary death in women compared with men (p = 0.002). Conclusions: Only a small amount of the sex differential in coronary death could be explained by differences in the prevalence of classic risk factors. Alternative explanations are required to explain the age-related attenuation of the sex difference in CHD risk. © Mary Ann Liebert, Inc.published_or_final_versio

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Mechanical Properties of Silicon Nanowires

Nanowires have been taken much attention as a nanoscale building block, which can perform the excellent mechanical function as an electromechanical device. Here, we have performed atomic force microscope (AFM)-based nanoindentation experiments of silicon nanowires in order to investigate the mechanical properties of silicon nanowires. It is shown that stiffness of nanowires is well described by Hertz theory and that elastic modulus of silicon nanowires with various diameters from ~100 to ~600 nm is close to that of bulk silicon. This implies that the elastic modulus of silicon nanowires is independent of their diameters if the diameter is larger than 100 nm. This supports that finite size effect (due to surface effect) does not play a role on elastic behavior of silicon nanowires with diameter of >100 nm

Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer

<p>Abstract</p> <p>Background</p> <p>Activating mutations of the epidermal growth factor receptor (<it>EGFR</it>) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.</p> <p>Methods</p> <p>Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.</p> <p>Results</p> <p>EGFR protein overexpression (EGFR_high) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFR_hightumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFR_low). Microarray analysis did not reveal any differences in gene expression between EGFR_highand EGFR_lowtumours. Conversely, in EGFR_hightumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFR_high(n=3) and mutated/EGFR_lowtumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.</p> <p>Conclusions</p> <p>Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.</p

A Powerful Test of Parent-of-Origin Effects for Quantitative Traits Using Haplotypes

Imprinting is an epigenetic phenomenon where the same alleles have unequal transcriptions and thus contribute differently to a trait depending on their parent of origin. This mechanism has been found to affect a variety of human disorders. Although various methods for testing parent-of-origin effects have been proposed in linkage analysis settings, only a few are available for association analysis and they are usually restricted to small families and particular study designs. In this study, we develop a powerful maximum likelihood test to evaluate the parent-of-origin effects of SNPs on quantitative phenotypes in general family studies. Our method incorporates haplotype distribution to take advantage of inter-marker LD information in genome-wide association studies (GWAS). Our method also accommodates missing genotypes that often occur in genetic studies. Our simulation studies with various minor allele frequencies, LD structures, family sizes, and missing schemes have uniformly shown that using the new method significantly improves the power of detecting imprinted genes compared with the method using the SNP at the testing locus only. Our simulations suggest that the most efficient strategy to investigate parent-of-origin effects is to recruit one parent and as many offspring as possible under practical constraints. As a demonstration, we applied our method to a dataset from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to test the parent-of-origin effects of the SNPs within the PPARGC1A, MTP and FABP2 genes on diabetes-related phenotypes, and found that several SNPs in the MTP gene show parent-of-origin effects on insulin and glucose levels