The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Racial/Ethnic Disparities in Exercise and Dietary Behaviors of Middle-Aged and Older Adults

BackgroundDifferences in health behaviors may be important contributors to racial/ethnic disparities in the health status of adults. Studies to date have not compared whether there are health behavior differences in exercise and dietary behaviors among middle-age and older adults in the four largest racial/ethnic categories.ObjectiveTo investigate racial/ethnic differences in exercise and dietary behaviors of middle-aged and older adults.DesignWe used data from the 2007 California Health Interview Survey. Multivariable logistic regression was used to examine interactions between age and race/ethnicity in predicting two categories of health behaviors. Analyses were conducted adjusting for sociodemographic characteristics, health insurance status, and healthcare utilization.ParticipantsA population-based sample of 33,189 California adults 45 years old and older: 26,522 non-Hispanic whites, 1,686 African American/blacks, 2,565 Asian/Pacific Islanders (1,741 English-proficient; 824 limited English-proficient), and 2,416 Latinos (1,538 English-proficient; 878 limited English-proficient).Main measuresSelf-report leisure-time physical activity (moderate and vigorous) and daily consumption of fruits and vegetables.Key resultsRacial/ethnic minorities generally engaged in less healthy exercise and dietary behaviors than whites, with differences more pronounced in middle adulthood. The disparities were the greatest among English-proficient minorities. Specifically, among middle-aged respondents, all racial/ethnic minorities engaged in less vigorous physical activity than whites (ORs range = 0.28 to 0.73; 95% CI range = 0.16-1.00). Additionally, middle-aged, English-proficient minorities engaged in less moderate physical activity compared to whites (ORs range =0.57 to 0.67; 95% CI range = 0.45-0.79). Furthermore, middle-aged, English-proficient Latinos had a poorer diet than whites (OR = 0.54; 0.39-0.75). Few significant racial/ethnic differences emerged in the exercise and dietary behaviors of older adults.ConclusionsRacial/ethnic disparities in exercise and dietary behaviors are most notable among middle-aged, acculturated minorities. Results highlight the need to promote positive exercise and dietary behaviors during critical preventive ages, when racial/ethnic disparities are large and the potential to prevent chronic disease is great

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background: Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m2. The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention. Methods: We compared treatment need based on BMI classification with four adiposity-based criteria: percentage body fat (%BF), considered both alone and in relation to metabolic syndrome risk (MS), waist circumference (WC), as an index of abdominal fat, and Body Fat Mass Index (BFMI, calculated as fat mass in kg divided by height in m2) in 63 volunteers (23 men and 40 women, aged 20 – 65 years). Results: According to the classification based on BMI, 6.3% of subjects were underweight, 52.4% were normal weight, 30.2% were overweight, and 11.1% were obese. Agreement between the BMI categories and the other classification criteria categories varied; the most notable discrepancy emerged in the underweight and overweight categories. BMI compared to almost all of the other adiposity-based criteria, identified a lower percentage of subjects for whom treatment would be recommended. In particular, the proportion of subjects for whom clinicians would strongly recommend weight loss on the basis of their BMI (11.1%) was significantly lower than those identified according to WC (25.4%, p = 0.004), %BF (28.6%, p = 0.003), and MS (33.9%, p = 0.002). Conclusion: The use of the BMI alone, as opposed to an assessment based on body composition, to identify individuals needing lifestyle intervention may lead to unfortunate misclassifications. Population-specific data on the relationships between body composition, morbidity, and mortality are needed to improve the diagnosis and treatment of at-risk individual

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product

Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Previous studies have examined the association between polymorphisms in the coagulation factor VII gene and the risk of coronary heart disease (CHD), but those studies have been inconclusive. This study was conducted to assess the associations between these polymorphisms and CHD and evaluated the associations in different ethnicities.</p> <p>Methods</p> <p>Literature-based searching was conducted to collect data and two methods, namely fixed-effects and random-effects, were performed to pool the odds ratio (OR), together with the 95% confidence interval (CI). Publication bias and between-study heterogeneity were also examined.</p> <p>Results</p> <p>Thirty-nine case-control studies of the three polymorphisms, R353Q (rs6046), HVR4 and -323Ins10 (rs36208070) in factor VII gene and CHD were enrolled in this meta-analysis, including 9,151 cases of CHD and 14,099 controls for R353Q, 2,863 cases and 2,727 controls for HVR4, and 2,862 cases and 4,240 controls for -323Ins10. Significant association was only found in Asian population for R353Q (Q vs R), with pooled OR of 0.70(95%CI: 0.55, 0.90). For the -323Ins10 polymorphism (10 vs 0), we found significant associations in both Asian and European populations, with pooled ORs of 0.74(95%CI: 0.61, 0.88) and 0.63(95%CI: 0.53, 0.74), respectively. Marginal significant association was found between HVR4 (H7 vs H5+H6) and CHD (OR = 0.88, 95% CI: 0.78, 1.00). There was no evidence of publication bias, but between-study heterogeneity was found in the analyses.</p> <p>Conclusions</p> <p>The -323Ins10 polymorphism in factor VII gene is significantly associated with CHD in both Asian and European populations, while R353Q polymorphism showed trend for association with CHD in Asians. Lack of association was found for HVR4 polymorphism. Further studies are needed to confirm the association, especially for -323Ins10 polymorphism.</p

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Prevalence of dementia and Alzheimer's disease in elders of nursing homes and a senior center of Durango City, Mexico

BACKGROUND: Epidemiological reports about dementia and Alzheimer's disease (AD) in elderly people from developing countries are scarce. Therefore, we sought to determine the prevalences of dementia and AD in a population of nursing home residents and senior center attendees of Durango City, Mexico, and to determine whether any socio-demographic characteristics from the subjects associated with dementia or AD exist. METHODS: One hundred and fifty-five residents of two nursing homes and 125 attendees of a senior center were examined for dementia and Alzheimer's disease. All subjects were tested by the mini-mental state examination, and those who scored twenty-four or less underwent psychiatric and neurological evaluations. Diagnosis of dementia, AD and vascular dementia (VaD) was based on the DSM-IV criteria. Socio-demographic characteristics from each participant were also obtained. RESULTS: Residents of nursing homes found to suffer from dementia were 25 out of 155 (16.1%). Eighteen of them (11.6%) had AD, and seven (4.5%) had VaD. None of the attendees of the senior center suffered from dementia. Dementia (pooled AD and VaD cases) correlated with white ethnicity (OR = 3.2; 95%CI = 1.28–8.31), and a history of unemployment (OR = 6.46; 95%CI = 1.42–25.97), while AD correlated with journeymen occupations (OR = 4.55; 95%CI = 1.00–19.29). CONCLUSION: Prevalence of dementia in residents of nursing homes found in this study is much lower than reported from more industrialized countries. AD was more frequent than VaD. Ethnicity and occupation showed effects on the prevalence figures. The prevalence of dementia found has implications for the optimum kind of health care that nursing homes should provide to their residents

Ethnic Differences in Body Composition and Obesity Related Risk Factors: Study in Chinese and White Males Living in China

The purpose of this cross-sectional observational study was to identify ethnic differences in body composition and obesity-related risk factors between Chinese and white males living in China. 115 Chinese and 114 white male pilots aged 28–63 years were recruited. Fasting body weight, height and blood pressure were measured following standard procedures. Whole-body and segmental body composition were measured using an 8-contact electrode bioimpedance analysis (BIA) system. Fasting serum glucose, fasting plasma total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed using automatic biochemistry analyzer. After adjusting for age and body mass index (BMI), Chinese males had significantly higher percentage of body fat (PBF) both with respect to whole body (Chinese: 23.7%±0.2% vs. Whites: 22.4%±0.2%) and the trunk area (Chinese: 25.0%±0.3% vs. Whites: 23.2%±0.3%) compared to their white counterparts. At all BMIs, Chinese males had significantly higher fasting glucose levels (Chinese: 5.7±1.0 mmol/L vs. Whites: 5.2±1.0 mmol/L) but lower high-density lipoprotein levels (Chinese: 0.8±1.0 mmol/L vs. Whites: 1.0±1.0 mmol/L) than white males. In addition, a marginally significantly higher diastolic blood pressure was found among Chinese men than that among white men (Chinese: 80±1.0 mmHg vs. Whites: 77±1.0 mmHg). Chinese males had more body fat and a greater degree of central fat deposition pattern than that seen in white males in the present study. Furthermore, data on blood pressure, fasting glucose and blood lipids suggest that Chinese men may be more prone to obesity-related risk factors than white men