Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity.

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/β-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in β-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/β-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity

Reasons and Means to Model Preferences as Incomplete

Literature involving preferences of artificial agents or human beings often assume their preferences can be represented using a complete transitive binary relation. Much has been written however on different models of preferences. We review some of the reasons that have been put forward to justify more complex modeling, and review some of the techniques that have been proposed to obtain models of such preferences

Suicidal Thoughts and Behaviors Among Transgender Adults in Relation to Education, Ethnicity, and Income: A Systematic Review

Introduction: This systematic review assessed the impact of race/ethnicity, education, and income on transgender individual's lifetime experience of suicidal thoughts and behaviors (SITB) in gray and published literature (1997–2017). Methods: Sixty four research projects (108 articles) were identified in WorldCat, PubMed, and Google Scholar. Articles were included if they were published in Canada or the United States, included original quantifiable data on transgender SITBs, and had ≥5 participants, at least 51% of whom were ≥18 years. Results: Across all projects suicide ideation averaged 46.55% and attempts averaged 27.19%. The majority of participants were Caucasian, whereas the highest rate of suicide attempts (55.31%) was among First Nations, who accounted for <1.5% of participants. Caucasians, by contrast, had the lowest attempt rate (36.80%). More participants obtained a bachelor's degree and fewer an associate or technical degree than any other level of education. Suicide attempts were highest among those with ≤some high school (50.70%) and lowest among those with an advanced degree (30.25%). More participants made an income of $20–$50,000/year and less $10–$20,000 than any other income bracket. Conclusion: SITBs, among the transgender population, are both universally high and impacted by race/ethnicity, educational attainment, and income. These findings may be useful in creating culturally and factually informed interventions for transgender individuals experiencing SITBs and in informing future research on this topic

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells

We have sequenced the promoter region of the murine asparagine synthetase gene and examined its methylation profile in the CpG islands of L-asparaginase-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (prototrophs). In the former, complete methylation of the CpG island is correlated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles, as do cells of the intrinsically asparagine-independent lines L1210 and EL4. A similar phenomenon was seen in normal splenic cells of adult mice. This was age related: no methylation was found in weanlings, but up to 45% of gene copies in animals 18 weeks or older were methylated. It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

Does patient satisfaction of general practice change over a decade?

Background The Patient Participation Program (PPP) was a patient satisfaction survey endorsed by the Royal Australian College of General Practitioners and designed to assist general practitioners in continuous quality improvement (CQI). The survey was been undertaken by 3500 practices and over a million patients between 1994 and 2003. This study aimed to use pooled patient questionnaire data to investigate changes in satisfaction with primary care over time. Methods The results of 10 years of the PPP surveys were analyzed with respect to 10 variables including the year of completion, patient age, gender, practice size, attendance at other doctors, and whether the practice had previously undertaken the survey. Comparisons were made using Logistic Generalized Estimating Equations (LGEE). Results There was a very high level of satisfaction with general practice in Australia (99% of respondents). An independent indicator of satisfaction was created by pooling the results of 12 questions. This new indicator had a greater variance than the single overall satisfaction question. Participants were shown to have higher levels of satisfaction if they were male, older, did not attend other practitioners or the practice was small in size. A minimal improvement in satisfaction was detected in this pooled indicator for the second or third survey undertaken by a practice. There was however no statistically significant change in pooled satisfaction with the year of survey. Conclusion The very high level of satisfaction made it difficult to demonstrate change. It is likely that this and the presentation of results made it difficult for GPs to use the survey to improve their practices. A more useful survey would be more sensitive to detect negative patient opinions and provide integrated feedback to GPs. At present, there are concerns about the usefulness of the PPP in continuous quality improvement in general practice.James Allan, Peter Schattner, Nigel Stocks and Emmae Ramsa

Does patient satisfaction of general practice change over a decade?

Background The Patient Participation Program (PPP) was a patient satisfaction survey endorsed by the Royal Australian College of General Practitioners and designed to assist general practitioners in continuous quality improvement (CQI). The survey was been undertaken by 3500 practices and over a million patients between 1994 and 2003. This study aimed to use pooled patient questionnaire data to investigate changes in satisfaction with primary care over time. Methods The results of 10 years of the PPP surveys were analyzed with respect to 10 variables including the year of completion, patient age, gender, practice size, attendance at other doctors, and whether the practice had previously undertaken the survey. Comparisons were made using Logistic Generalized Estimating Equations (LGEE). Results There was a very high level of satisfaction with general practice in Australia (99% of respondents). An independent indicator of satisfaction was created by pooling the results of 12 questions. This new indicator had a greater variance than the single overall satisfaction question. Participants were shown to have higher levels of satisfaction if they were male, older, did not attend other practitioners or the practice was small in size. A minimal improvement in satisfaction was detected in this pooled indicator for the second or third survey undertaken by a practice. There was however no statistically significant change in pooled satisfaction with the year of survey. Conclusion The very high level of satisfaction made it difficult to demonstrate change. It is likely that this and the presentation of results made it difficult for GPs to use the survey to improve their practices. A more useful survey would be more sensitive to detect negative patient opinions and provide integrated feedback to GPs. At present, there are concerns about the usefulness of the PPP in continuous quality improvement in general practice.James Allan, Peter Schattner, Nigel Stocks and Emmae Ramsa

Identification of Muscle-Specific MicroRNAs in Serum of Muscular Dystrophy Animal Models: Promising Novel Blood-Based Markers for Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMDJ), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMDJ. Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy