Prevalence of Obesity and the Relationship between the Body Mass Index and Body Fat: Cross-Sectional, Population-Based Data

Background: Anthropometric measures such as the body mass index (BMI) and waist circumference are widely used as convenient indices of adiposity, yet there are limitations in their estimates of body fat. We aimed to determine the prevalence of obesity using criteria based on the BMI and waist circumference, and to examine the relationship between the BMI and body fat.Methodology/Principal Findings: This population-based, cross-sectional study was conducted as part of the Geelong Osteoporosis Study. A random sample of 1,467 men and 1,076 women aged 20&ndash;96 years was assessed 2001&ndash;2008. Overweight and obesity were identified according to BMI (overweight 25.0&ndash;29.9 kg/m2; obesity 30.0 kg/m2) and waist circumference (overweight men 94.0–101.9 cm; women 80.0–87.9 cm; obesity men 102.0 cm, women $88.0 cm); body fat mass was assessed using dual energy X-ray absorptiometry; height and weight were measured and lifestyle factors documented by self-report. According to the BMI, 45.1% (95%CI 42.4&ndash;47.9) of men and 30.2% (95%CI 27.4&ndash;33.0) of women were overweight and a further 20.2% (95%CI 18.0&ndash;22.4) of men and 28.6% (95%CI 25.8&ndash;31.3) of women were obese. Using waist circumference, 27.5% (95%CI 25.1&ndash;30.0) of men and 23.3% (95%CI 20.8&ndash;25.9) of women were overweight, and 29.3% (95%CI 26.9&ndash;31.7) of men and 44.1% (95%CI 41.2&ndash;47.1) of women, obese. Both criteria indicate that approximately 60% of the population exceeded recommended thresholds for healthy body habitus. There was no consistent pattern apparent between BMI and energy intake. Compared with women, BMI overestimated adiposity in men, whose excess weight was largely attributable to muscular body builds and greater bone mass. BMI also underestimated adiposity in the elderly. Regression models including gender, age and BMI explained 0.825 of the variance in percent body fat.Conclusions/Significance: As the BMI does not account for differences in body composition, we suggest that gender- and age-specific thresholds should be considered when the BMI is used to indicate adiposity.<br /

Moving towards a population health approach to the primary prevention of common mental disorders

There is a need for the development of effective universal preventive approaches to the common mental disorders, depression and anxiety, at a population level. Poor diet, physical inactivity and smoking have long been recognized as key contributors to the high prevalence noncommunicable diseases. However, there are now an increasing number of studies suggesting that the same modifiable lifestyle behaviors are also risk factors for common mental disorders. In this paper we point to the emerging data regarding lifestyle risk factors for common mental disorders, with a particular focus on and critique of the newest evidence regarding diet quality. On the basis of this most recent evidence, we consequently argue for the inclusion of depression and anxiety in the ranks of the high prevalence noncommunicable diseases influenced by habitual lifestyle practices. We believe that it is both feasible and timely to begin to develop effective, sustainable, population-level prevention initiatives for the common mental illnesses that build on the established and developing approaches to the noncommunicable somatic diseases.<br /

Structural Basis for alpha-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers

Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein-protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide-oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization

Serum 25-Hydroxyvitamin D Concentrations and Season-Specific Correlates in Japanese Adults

Background: Several lines of evidence indicate an important role for vitamin D in the prevention of a range of diseases. Blood vitamin D levels show clear seasonal variation; however, data on the determinants of vitamin D status for each season are limited. We investigated the association between lifestyle and serum vitamin D concentration by season in Japanese workers. Methods: Subjects were 312 men and 217 women aged 21 to 67 years who worked in municipal offices in Northern Kyushu, Japan and participated in a periodic checkup in July or November. Multiple linear regression analysis was used to examine the association between serum 25-hydroxivitamin D concentrations and lifestyle factors for each season. Results: Mean serum 25-hydroxyvitamin D concentration was 27.4 ng/ml (68.4 nmol/L) and 21.4 ng/ml (53.4 nmol/L) for workers surveyed in July and November, respectively (P \u3c 0.001); the prevalence of vitamin D deficiency ( both sexes) and nonsmoking and physical activity (in men) were significantly associated with higher concentrations of serum 25-hydroxyvitamin D. In summer, fish/shellfish intake was associated with higher serum 25- hydroxyvitamin D concentrations in women. Conclusions: Vitamin D deficiency is common in Japanese workers during seasons with limited sunlight. The lifestyle correlates of favorable vitamin D status in November were physical activity, dietary vitamin D intake, and nonsmoking

The CXC-Chemokine CXCL4 Interacts with Integrins Implicated in Angiogenesis

The human CXC-chemokine CXCL4 is a potent inhibitor of tumor-induced angiogenesis. Considering that CXCL4 is sequestered in platelet α-granules and released following platelet activation in the vicinity of vessel wall injury, we tested the hypothesis that CXCL4 might function as a ligand for integrins. Integrins are a family of adhesion receptors that play a crucial role in angiogenesis by regulating early angiogenic processes, such as endothelial cell adhesion and migration. Here, we show that CXCL4 interacts with αvβ3 on the surface of αvβ3-CHO. More importantly, human umbilical vein endothelial cells adhere to immobilized CXCL4 through αvβ3 integrin, and also through other integrins, such as αvβ5 and α5β1. We further demonstrate that CXCL4-integrin interaction is of functional significance in vitro, since immobilized CXCL4 supported endothelial cell spreading and migration in an integrin-dependent manner. Soluble CXCL4, in turn, inhibits integrin-dependent endothelial cell adhesion and migration. As a whole, our study identifies integrins as novel receptors for CXCL4 that may contribute to its antiangiogenic effect

Cross-sectional analysis of association between socioeconomic status and utilization of primary total hip joint replacements 2006-7 : Australian orthopaedic association national joint replacement registry

Background The utilization of total hip replacement (THR) surgery is rapidly increasing, however few data examine whether these procedures are associated with socioeconomic status (SES) within Australia. This study examined primary THR across SES for both genders for the Barwon Statistical Division (BSD) of Victoria, Australia.Methods Using the Australian Orthopaedic Association National Joint Replacement Registry data for 2006&ndash;7, primary THR with a diagnosis of osteoarthritis (OA) among residents of the BSD was ascertained. The Index of Relative Socioeconomic Disadvantage was used to measure SES; determined by matching residential addresses with Australian Bureau of Statistics census data. The data were categorised into quintiles; quintile 1 indicating the most disadvantaged. Age- and sex-specific rates of primary THR per 1,000 person years were reported for 10-year age bands using the total population at risk.Results Females accounted for 46.9% of the 642 primary THR performed during 2006&ndash;7. THR utilization per 1,000 person years was 1.9 for males and 1.5 for females. The highest utilization of primary THR was observed in those aged 70&ndash;79&thinsp;years (males 6.1, and females 5.4 per 1,000 person years). Overall, the U-shaped pattern of THR across SES gave the appearance of bimodality for both males and females, whereby rates were greater for both the most disadvantaged and least disadvantaged groups.Conclusions Further work on a larger scale is required to determine whether relationships between SES and THR utilization for the diagnosis of OA is attributable to lifestyle factors related to SES, or alternatively reflects geographic and health system biases. Identifying contributing factors associated with SES may enhance resource planning and enable more effective and focussed preventive strategies for hip OA. <br /

Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach

Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors

High Sugar-Induced Insulin Resistance in Drosophila Relies on the Lipocalin Neural Lazarillo

In multicellular organisms, insulin/IGF signaling (IIS) plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD) that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D) patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz), a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome

Convergent, Parallel and Correlated Evolution of Trophic Morphologies in the Subfamily Schizothoracinae from the Qinghai-Tibetan Plateau

Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan plateau (QTP) and adjacent areas are characterized by being highly adaptive to the cold and hypoxic environment of the plateau, as well as by a high degree of diversity in trophic morphology due to resource polymorphisms. Although convergent and parallel evolution are prevalent in the organisms of the QTP, it remains unknown whether similar evolutionary patterns have occurred in the schizothoracine fishes. Here, we constructed for the first time a tentative molecular phylogeny of the schizothoracine fishes based on the complete sequences of the cytochrome b gene. We employed this molecular phylogenetic framework to examine the evolution of trophic morphologies. We used Pagel's maximum likelihood method to estimate the evolutionary associations of trophic morphologies and food resource use. Our results showed that the molecular and published morphological phylogenies of Schizothoracinae are partially incongruent with respect to some intergeneric relationships. The phylogenetic results revealed that four character states of five trophic morphologies and of food resource use evolved at least twice during the diversification of the subfamily. State transitions are the result of evolutionary patterns including either convergence or parallelism or both. Furthermore, our analyses indicate that some characters of trophic morphologies in the Schizothoracinae have undergone correlated evolution, which are somewhat correlated with different food resource uses. Collectively, our results reveal new examples of convergent and parallel evolution in the organisms of the QTP. The adaptation to different trophic niches through the modification of trophic morphologies and feeding behaviour as found in the schizothoracine fishes may account for the formation and maintenance of the high degree of diversity and radiations in fish communities endemic to QTP