Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

A Danish population-based cohort study of newly diagnosed asthmatic children's care pathway – adherence to guidelines

<p>Abstract</p> <p>Background</p> <p>Asthma is the most common chronic disease in childhood. Large variations exist concerning the number of children being treated by general practitioners and by specialists. Consequently, health related costs due to this disease vary as care by specialists is more expensive compared with care by general practitioners. Little is known of the consequences of these variations concerning the quality of care. The aim of the study was to analyse associations between care providers and adherence to guidelines concerning frequency of contacts with the health service due to asthma.</p> <p>Methods</p> <p>A cohort study was performed of 36,940 incident asthmatic children's (aged 6–14) contacts with the health service using the unique personal registration number to link data from five national registries. The prevalence ratios were calculated for associations between provider (general practitioner, primary care specialist, hospital specialist or both GP and specialist) and adherence with guidelines concerning three indicators of quality of care pathway: 1) diagnostic examination of lung function at start of medical treatment 2) follow-up the first six months and 3) follow-up the next six months. The associations were adjusted for sex, age, socioeconomic status, county, and severity of disease.</p> <p>Results</p> <p>Most children (70.3%) had only been seen by their GP. About 80% of the children were treated with inhaled steroids, 70% were treated with inhaled steroids as well as inhaled beta2agonists and 13% were treated with inhaled beta2agonists only. A total of 12,650 children (34.2%) had no registered asthma-related contacts with the health service except when redeeming prescriptions. Care was in accordance with guidelines in all three indicators of quality in 7% of the cases (GPs only: 3%, primary care specialists only: 16%, hospital specialists: 28%, and both GP and specialists: 13%). Primary care specialists had a 5.01, hospital specialists a 8.81 and both GP and specialists a 4.32 times higher propensity to provide a clinical pathway according to guidelines compared to GPs alone.</p> <p>Conclusion</p> <p>The majority of the children were seen in general practice. Hospital specialists provided care in accordance with guidelines nine times more often compared with GPs, but still only one quarter of these children had pathways in accordance with guidelines. It is relevant to study further if these lacks of adherence to guidelines have implications for the asthmatic children or if guidelines are too demanding concerning frequency of follow-up or if asthmatic children should be stratified to different care pathways.</p

Assessing the congruence of thermal niche estimations derived from distribution and physiological data. A test using diving beetles.

A basic aim of ecology is to understand the determinants of organismal distribution, the niche concept and species distribution models providing key frameworks to approach the problem. As temperature is one of the most important factors affecting species distribution, the estimation of thermal limits is crucially important for inferring range constraints. It is expectable that thermal physiology data derived from laboratory experiments and species' occurrences may express different aspects of the species' niche. However, there is no study systematically testing this prediction in a given taxonomic group while controlling by potential phylogenetic inertia. We estimate the thermal niches of twelve Palaearctic diving beetles species using physiological data derived from experimental analyses in order to examine the extent to which these coincided with those estimated from distribution models based on observed occurrences. We found that thermal niche estimates derived from both approaches lack general congruence, and these results were similar before and after controlling by phylogeny. The congruence between potential distributions obtained from the two different procedures was also explored, and we found again that the percentage of agreement were not very high (~60%). We confirm that both thermal niche estimates derived from geographical and physiological data are likely to misrepresent the true range of climatic variation that these diving beetles are able to tolerate, and so these procedures could be considered as incomplete but complementary estimations of an inaccessible reality

Ginseng and ginkgo biloba effects on cognition as modulated by cardiovascular reactivity: a randomised trial

Background There is some evidence to suggest that ginseng and Ginkgo biloba can improve cognitive performance, however, very little is known about the mechanisms associated with such improvement. Here, we tested whether cardiovascular reactivity to a task is associated with cognitive improvement. Methodology/Principal findings Using a double-blind, placebo controlled, crossover design, participants (N = 24) received two doses of Panax Ginseng (500, 1000 mg) or Ginkgo Biloba (120, 240 mg) (N = 24), and underwent a series of cognitive tests while systolic, diastolic, and heart rate readings were taken. Ginkgo Biloba improved aspects of executive functioning (Stroop and Berg tasks) in females but not in males. Ginseng had no effect on cognition. Ginkgo biloba in females reversed the initial (i.e. placebo) increase in cardiovascular reactivity (systolic and diastolic readings increased compared to baseline) to cognitive tasks. This effect (reversal) was most notable after those tasks (Stroop and Iowa) that elicited the greatest cardiovascular reactivity during placebo. In males, although ginkgo also decreased cardiovascular readings, it did so from an initial (placebo) blunted response (i.e. decrease or no change from baseline) to cognitive tasks. Ginseng, on the contrary, increased cardiovascular readings compared to placebo. Conclusions/Significance These results suggest that cardiovascular reactivity may be a mechanism by which ginkgo but not ginseng, in females is associated with certain forms of cognitive improvement

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA

Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model

Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D2 autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2–6.0; P=0.01). Analyses of ∼1000 stage I–III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC