Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study).

Marijuana use has been associated with increased appetite, high caloric diet, acute increase in blood pressure, and decreases in high-density lipoprotein cholesterol and triglycerides. Marijuana is the most commonly used illicit drug in the United States, but its long-term effects on body mass index (BMI) and cardiovascular risk factors are unknown. Using 15 years of longitudinal data from 3,617 black and white young adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors. Of the 3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was associated with male gender, tobacco smoking, and other illicit drug use. More extensive marijuana use was associated with a higher caloric intake (2,746 kcal/day in never users to 3,365 kcal/day in those who used marijuana for > or = 1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl or 0.95 to 1.13 mmol/L, all p values for trend < 0.001), but not with higher BMI and lipid and glucose levels. In multivariate analysis, the associations between marijuana use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in marijuana users. In conclusion, although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs. other PFOs.

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score. METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of ≤6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant. RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group. CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

Predicted effect of climate change on the invasibility and distribution of the Western corn root-worm

1 Insect pests, biological invasions and climate change are considered to representmajor threats to biodiversity, ecosystem functioning, agriculture and forestry.Deriving hypothesis of contemporary and/or future potential distributions of insectpests and invasive species is becoming an important tool for predicting the spatialstructure of potential threats.2 The western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is apest of maize in North America that has invaded Europe in recent years, resultingin economic costs in terms of maize yields in both continents. The present studyaimed to estimate the dynamics of potential areas of invasion by the WCR under aclimate change scenario in the Northern Hemisphere. The areas at risk under thisscenario were assessed by comparing, using complementary approaches, the spatialprojections of current and future areas of climatic favourability of the WCR. Spatialhypothesis were generated with respect to the presence records in the native rangeof the WCR and physiological thresholds from previous empirical studies.3 We used a previously developed protocol specifically designed to estimatethe climatic favourability of the WCR. We selected the most biologicallyrelevant climatic predictors and then used multidimensional envelope (MDE) andMahalanobis distances (MD) approaches to derive potential distributions for currentand future climatic conditions.4 The results obtained showed a northward advancement of the upper physiologicallimit as a result of climate change, which might increase the strength of outbreaksat higher latitudes. In addition, both MDE and MD outputs predict the stability ofclimatic favourability for the WCR in the core of the already invaded area in Europe,which suggests that this zone would continue to experience damage from this pestin Europe.

Predicted effects of small decreases in energy expenditure on weight gain in adult women.

Small daily positive energy imbalances of 200 to 800 kJ (about 50 to 200 kcal) due to reduced resting energy expenditure (REE), reduced diet-induced thermogenesis, or physical inactivity are believed to predispose to obesity. However, estimates of the magnitude of the weight gain often fail to account for concurrent changes in body composition and increases in maintenance energy requirements as weight increases and energy equilibrium is re-established. Using previously reported data on body composition and REE in women and the energy cost of tissue deposition, we used mathematical models to predict the theoretical effect of a persistent reduction in energy expenditure on long-term weight gain, assuming no adaptation in energy intake. The analyses indicate the following effects of a reduced level of energy expenditure in lean and obese women: (i) REE rises more slowly with increasing degrees of obesity due to a declining proportion of the more metabolically active fat-free mass; so, for the same positive energy balance, a significantly greater weight gain is expected for obese than for lean women before energy equilibrium is re-established; (ii) due to the greater energy density of adipose tissue, the time course of weight gain to achieve energy balance is longer for obese subjects: in general, this is approximately five years for lean and ten years for obese women; (iii) the magnitude of weight gain of lean women in response to a reduced energy expenditure of 200 to 800 kJ/day is only about 3 to 15 kg, amounts insufficient to explain severe obesity.

Carotid-Subclavian Artery Index : Validation of an Echocardiographic Index to Detect Coarctation : P67

Introduction: Due to patency of the arterial duct and the parallel circulation during the fetal life, coarctation remains a difficult diagnosis prenatally and even shortly after birth. Fisrtly, our study aimed to assess accuracy of a new cardiographie index based on morphologie measurements of the distal aortic arch, the Carotid-Subclavian Artery Index (CSA Index), the ratio of the distal transverse aortic arch diameter to the distance between the left carotid artery and the left subclavian artery, in detecting coarctation in newborns, infants and children, independently of other cardiac lesions. Secondly, to assess the additive value of another morphologie index in predicting coarctation, the 1/0 ratio, the ratio of isthmus to descending aorta diameter. Methods: It is a retrospective cohort study in a tertiary care children's hospital. Offline echocardiographic measurements of great vessels and aortic arch dimensions were done in 69 patients with coarctation. We calculate their CSA index, and their 1/0 ratio. Values of CSA Index and 1/0 ratio from coarctation group were compared with those from a normal local control population. Results: 69 echocardiograms from patients with coarctation were analysed. Compared with controls, patients with coarctation had a significantly lower CSA index (0.88 ±0.49 vs 2.65 ±0.82, p <0.0001) and 1/0 ratio. The same significant difference was observed, independently of age and other associated defects, even complex ones. CSA Index confirmed its good sensitivity and specificity (99% and 96% respectively). This was not improved by adding the I/D ratio. Conclusions: An abnormal CSA index is highly suggestive of coarctation independently of age, of the presence of a patent ductus arteriosus or of other cardiac defects. The addition of another anatomie index, the I/D ratio, was not helpful in our study.

Assessing dispositional empathy in adults: A French validation of the Interpersonal Reactivity Index (IRI).

The goal of this study was to validate a French version of the Interpersonal Reactivity Index (IRI), a self-report questionnaire comprised of four subscales assessing affective (empathic concern and personal distress) and cognitive (fantasy and perspective taking) components of empathy. To accomplish this, 322 adults (18 to 89 years) completed the French version of the IRI (F-IRI). A confirmatory factor analysis confirmed the four-factor structure of the original IRI. The F-IRI showed good scale score reliability, test-retest reliability, and convergent validity, tested with the French version of the Empathy Quotient. These findings confirmed the reliability and validity of the F-IRI and suggest that the F-IRI is a useful instrument to measure self-reported empathy. In addition, we observed sex and age differences consistent with findings in the literature. Women reported higher scores in empathic concern and fantasy than men. Older adults reported less personal distress and less fantasy. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

The association between body mass index and patients' experiences with inpatient care.

OBJECTIVE: To explore the association between patients' body mass index (BMI) and their experiences with inpatient care. DESIGN: Cross-sectional. Mail survey. SETTING: University Hospital of Geneva. PARTICIPANTS: Questionnaires were mailed to 2385 eligible adult patients, 6 weeks after discharge (response rate = 69%). MAIN OUTCOME MEASURES: Patients' experiences with care were measured using the Picker inpatient survey questionnaire. BMI was calculated using self-reported height and weight. Main dependent variables were the global Picker patient experience (PPE-15) score and nine dimension-specific problem scores, scored from 0 (no reported problems) to 1 (all items coded as problems). We used linear regressions, adjusting for age, gender, education, subjective health, smoking and hospitalization, to assess the association between patients' BMI and their experiences with inpatient care. RESULTS: Of the patients, 4.8% were underweight, 50.8% had normal weight, 30.3% were overweight and 14.1% were obese. Adjusted analysis shows that compared with normal weight, obesity was significantly associated with fewer problematic items in the surgery-related information domain, and being underweight or overweight was associated with more problematic items in the involvement of family/friends domain. The global PPE-15 score was significantly higher (more problems) for underweight patients. CONCLUSIONS: Underweight patients, but not obese patients, reported more problems during hospitalization.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI </= 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's </= 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.

Regulation of the expression of Fit insect toxin locus genes in the root-associated biocontrol pseudomonad CHA0

The root-colonizing Pseudomonas fluorescens strain CHA0 is a biocontrol agent of soil-borne plant diseases caused by fungal and oomycete pathogens. Remarkably, this plant-beneficial pseudomonad is also endowed with potent insecticidal activity that depends on the production of a large protein toxin termed Fit (for P. fluorescens insecticidal toxin). In our present work, the genomic locus encoding the P. fluorescens insect toxin is subjected to a detailed molecular analysis. The Fit toxin gene fitD is flanked upstream by the fitABC genes and downstream by the fitE gene that encode the ABC transporter, membrane fusion, and outer membrane efflux components of a type I protein secretion system predicted to function in toxin export. The fitF, fitG, and fitH genes located downstream of fitE code for regulatory proteins having domain structures typical of signal transduction histidine kinases, LysR-type transcriptional regulators, and response regulators, respectively. The role of these insect toxin locus-associated control elements is being investigated with mutants defective for the regulatory genes and with GFP-based reporter fusions to putative promoter regions upstream of the transporter genes fitA and fitE, the toxin gene fitD, and the regulatory genes fitF and fitH. Our preliminary findings suggest that the three regulators interact with known global regulators of biocontrol factor expression to control Fit toxin expression and secretion.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Small airways function declines after allogeneic haematopoietic stem cell transplantation.

Bronchiolitis obliterans (BO) following allogeneic haematopoietic stem cell transplantation (HSCT) affects peripheral airways. Detection of BO is presently delayed by the low sensitivity of spirometry. We examined the relationship between peripheral airway function and time since HSCT, and compared it with spirometry and clinical indices in 33 clinically stable allogeneic HSCT recipients. The following measurements were performed: lung function, exhaled nitric oxide, forced oscillatory respiratory system resistance and reactance, acinar (S(acin)) and conductive airways ventilation heterogeneity and lung clearance index (LCI) measured by multiple breath nitrogen washout. 22 patients underwent repeat visits from which short-term changes were examined. Median time post HSCT was 12 months. Eight patients were clinically diagnosed as having BO. In multivariate analysis, time since HSCT was predicted by S(acin) and forced expiratory volume in 1 s % predicted. 20 patients had abnormal S(acin) with normal spirometry, whereas none had airflow obstruction with normal S(acin). S(acin) and LCI were the only measures to change significantly between two visits, with both worsening. Change in S(acin) was the only parameter to correlate with change in chronic graft-versus-host disease grade. In conclusion, peripheral airways ventilation heterogeneity worsens with time after HSCT. S(acin) may be more sensitive than spirometry in detecting BO at an early stage, which needs confirmation in a prospective study.