Body mass index and health-related quality of life among young Swiss men.

BACKGROUND: Studies about the association between body mass index (BMI) and health-related quality of life (HRQOL) are often limited, because they 1) did not include a broad range of health-risk behaviors as covariates; 2) relied on clinical samples, which might lead to biased results; and 3) did not incorporate underweight individuals. Hence, this study aims to examine associations between BMI (from being underweight through obesity) and HRQOL in a population-based sample, while considering multiple health-risk behaviors (low physical activity, risky alcohol consumption, daily cigarette smoking, frequent cannabis use) as well as socio-demographic characteristics. METHODS: A total of 5 387 young Swiss men (mean age = 19.99; standard deviation = 1.24) of a cross-sectional population-based study were included. BMI was calculated (kg/m²) based on self-reported height and weight and divided into 'underweight' (<18.5), 'normal weight' (18.5-24.9), 'overweight' (25.0-29.9) and 'obese' (≥30.0). Mental and physical HRQOL was assessed via the SF-12v2. Self-reported information on physical activity, substance use (alcohol, cigarettes, and cannabis) and socio-demographic characteristics also was collected. Logistic regression analyses were conducted to study the associations between BMI categories and below average mental or physical HRQOL. Substance use variables and socio-demographic variables were used as covariates. RESULTS: Altogether, 76.3% were normal weight, whereas 3.3% were underweight, 16.5% overweight and 3.9% obese. Being overweight or obese was associated with reduced physical HRQOL (adjusted OR [95% CI] = 1.58 [1.18-2.13] and 2.45 [1.57-3.83], respectively), whereas being underweight predicted reduced mental HRQOL (adjusted OR [95% CI] = 1.49 [1.08-2.05]). Surprisingly, obesity decreased the likelihood of experiencing below average mental HRQOL (adjusted OR [95% CI] = 0.66 [0.46-0.94]). Besides BMI, expressed as a categorical variable, all health-risk behaviors and socio-demographic variables were associated with reduced physical and/or mental HRQOL. CONCLUSIONS: Deviations from normal weight are, even after controlling for important health-risk behaviors and socio-demographic characteristics, associated with compromised physical or mental HRQOL among young men. Hence, preventive programs should aim to preserve or re-establish normal weight. The self-appraised positive mental well-being of obese men noted here, which possibly reflects a response shift, might complicate such efforts.

Validation of the Addiction Severity Index in French-speaking alcoholic patients.

OBJECTIVE: Evaluation of a French translation of the Addiction Severity Index (ASI) in 100 (78 male) alcoholic patients. METHOD: Validity of the instrument was assessed by measuring test-retest and interrater reliability, internal consistency and convergence and discrimination between items and scales. Concurrent validity was assessed by comparing the scores from the ASI with those obtained from three other clinimetric instruments. RESULTS: Test-retest reliability of ASI scores (after a 10-day interval) was good (r = 0.63 to r = 0.95). Interrater reliability was evaluated using six video recordings of patient interviews. Severity ratings assigned by six rates were significantly different (p < .05), but 72% of the ratings assigned by those who viewed the videos were within two points of the interviewer's severity ratings. Cronbach alpha coefficient of internal consistency varied from 0.58 to 0.81 across scales. The average item-to-scale convergent validity (r value) was 0.49 (range 0.0 to 0.84) for composite scores and 0.35 (range 0.00 to 0.68) for severity ratings, whereas discriminant validity was 0.11 on average (range-0.19 to 0.46) for composite scores and 0.12 (range-0.20 to 0.52) for severity ratings. Finally, concurrent validity with the following instruments was assessed: Severity of Alcoholism Dependence Questionnaire (40% shared variance with ASI alcohol scale), Michigan Alcoholism Screening Test (2% shared variance with ASI alcohol scale) and Hamilton Depression Rating Scale (31% shared variance with ASI psychiatric scale). CONCLUSIONS: The Addiction Severity Index covers a large scope of problems encountered among alcoholics and quantifies need for treatment. This French version presents acceptable criteria of reliability and validity.

Viral transport of DNA damage that mimics a stalled replication fork.

Adeno-associated virus type 2 (AAV2) infection incites cells to arrest with 4N DNA content or die if the p53 pathway is defective. This arrest depends on AAV2 DNA, which is single stranded with inverted terminal repeats that serve as primers during viral DNA replication. Here, we show that AAV2 DNA triggers damage signaling that resembles the response to an aberrant cellular DNA replication fork. UV treatment of AAV2 enhances the G2 arrest by generating intrastrand DNA cross-links which persist in infected cells, disrupting viral DNA replication and maintaining the viral DNA in the single-stranded form. In cells, such DNA accumulates into nuclear foci with a signaling apparatus that involves DNA polymerase delta, ATR, TopBP1, RPA, and the Rad9/Rad1/Hus1 complex but not ATM or NBS1. Focus formation and damage signaling strictly depend on ATR and Chk1 functions. Activation of the Chk1 effector kinase leads to the virus-induced G2 arrest. AAV2 provides a novel way to study the cellular response to abnormal DNA replication without damaging cellular DNA. By using the AAV2 system, we show that in human cells activation of phosphorylation of Chk1 depends on TopBP1 and that it is a prerequisite for the appearance of DNA damage foci.

Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage: A challenge for neuroprotection.

There is currently no approved neuroprotective pharmacotherapy for acute conditions such as stroke and cerebral asphyxia. One of the reasons for this may be the multiplicity of cell death mechanisms, because inhibition of a particular mechanism leaves the brain vulnerable to alternative ones. It is therefore essential to understand the different cell death mechanisms and their interactions. We here review the multiple signaling pathways underlying each of the three main morphological types of cell death - apoptosis, autophagic cell death and necrosis - emphasizing their importance in the neuronal death that occurs during cerebral ischemia and hypoxia-ischemia, and we analyze the interactions between the different mechanisms. Finally, we discuss the implications of the multiplicity of cell death mechanisms for the design of neuroprotective strategies.

Development and validation of a postmortem radiological alteration index: the RA-Index.

This study aimed to derive an index quantifying the state of alteration of cadavers by quantifying the presence of gas in the body using postmortem multidetector computed tomography (MDCT) imaging, and to validate the index by defining its sensitivity and specificity. The RA (radiological alteration)-index was derived from postmortem MDCT data from 118 nontraumatically deceased people. To validate the index, 100 additional scanned bodies (50 % traumatically deceased) were retrospectively examined by two independent observers. Presence of gas at 82 sites was assessed by a radiologist, whereas a forensic pathologist only investigated the seven sites used for the RA-index. The RA-index was highly correlated to the overall presence of gas in all 82 sites (R(2) = 0.98 in the derivation set and 0.85 in the validation set). Semiquantitative evaluation of gas presence in each site showed moderate reliability (Cohen's kappa range, 0.41-0.78); nevertheless, the overall RA-index was very reliable (ICC(2,1) = 0.95; 95 % CI 0.92-0.96). Examiner using the RA-index detected heart cavities full of gas with a sensitivity of 100 % (95 % CI 51.7-100) and a specificity of 98.8 % (92.6-99.9). We conclude that determining the presence of gas at seven sites is a valid means to measure the distribution of gas due to cadaveric alteration in the entire body. The RA-index is rapid, easy-to-use, and reliable for nonexperienced users, and it is a valid method to suspect the normal presence of gas from cadaveric alteration. MDCT can be used to screen for gas embolism and to give indications for gas composition analysis (gas chromatography).

Development of the first disease activity index for eosinophilic esophagitis: update on the EEsAI in 2012

Background and Aims: The international E EsAI s tudy g roup is currently d eveloping the first activity index ( EEsAI) specific for E osinophilic Esophagitis (EoE). G oal: T o develop, e valuate and validate the EEsAI. Methods: T he development c omprises three p hases: 1. Selection of c andidate items ( completed); 2. Evaluation of t he activity index i n a first patient cohort (in progress, p atient recruitment completed); and 3. Validation in a s econd EoE patient cohort. F ocus group interviews with patients were used in p hase 1 to g enerate patient r eported outcomes (PRO) according to g uidelines o f regulatory authorities (FDA a nd EMA), whereas the section of biologic items was developed by Delphi rounds o f international E oE experts from E urope and North America. Results: T he EEsAI has a modular c omposition to a ssess the following components o f EoE activity: p atient r eported outcomes, e ndoscopic activity, histologic activity, laboratory activity, a nd quality of l ife (QoL). Definitions for a ll aspects o f endoscopic and histologic appearance were e stablished by consensus r ounds a mong E oE experts. S ymptom a ssessment tools were c reated that t ake into account d ifferent food consistencies as w ell as f ood avoidance and specific processing strategies. The EEsAI i s currently e valuated in a cohort of a dult EoE patients since M arch 2 011 (patient recruitment completed). Conclusions: The EEsAI standardizes outcome assessment in EoE t rials. T he collaboration with i nternational E oE e xperts a s well as f ollowing o f the guidelines f rom regulatory authorities will lead to its wide applicability.

Reliability and validity of the cross-culturally adapted French version of the Core Outcome Measures Index (COMI) in patients with low back pain.

PURPOSE: To conduct a cross-cultural adaptation of the Core Outcome Measures Index (COMI) into French according to established guidelines. METHODS: Seventy outpatients with chronic low back pain were recruited from six spine centres in Switzerland and France. They completed the newly translated COMI, and the Roland Morris disability (RMQ), Dallas Pain (DPQ), adjectival pain rating scale, WHO Quality of Life, and EuroQoL-5D questionnaires. After ~14 days RMQ and COMI were completed again to assess reproducibility; a transition question (7-point Likert scale; "very much worse" through "no change" to "very much better") indicated any change in status since the first questionnaire. RESULTS: COMI whole scores displayed no floor effects and just 1.5% ceiling effects. The scores for the individual COMI items correlated with their corresponding full-length reference questionnaire with varying strengths of correlation (0.33-0.84, P < 0.05). COMI whole scores showed a very good correlation with the "multidimensional" DPQ global score (Rho = 0.71). 55 patients (79%) returned a second questionnaire with no/minimal change in their back status. The reproducibility of individual COMI 5-point items was good, with test-retest differences within one grade ranging from 89% for 'social/work disability' to 98% for 'symptom-specific well-being'. The intraclass correlation coefficient for the COMI whole score was 0.85 (95% CI 0.76-0.91). CONCLUSIONS: In conclusion, the French version of this short, multidimensional questionnaire showed good psychometric properties, comparable to those reported for German and Spanish versions. The French COMI represents a valuable tool for future multicentre clinical studies and surgical registries (e.g. SSE Spine Tango) in French-speaking countries.

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.

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)

Physical activity modulates heat shock protein-72 expression and limits oxidative damage accumulation in a healthy elderly population aged 60 90 years

BACKGROUND: Reactive oxygen species production increases during aging, whereas protective mechanisms such as heat shock proteins (HSPs) or antioxidant capacity are depressed. Physical activity has been hypothesized to provide protection against oxidative damage during aging, but results remain controversial. This study aimed to investigate the effect of different levels of physical activity during aging on Hsp72 expression and systemic oxidative stress at rest and in response to maximal exercise. METHODS: Plasma antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), thiobarbituric acid-reactive species (TBARS), advanced oxidized proteins products (AOPP), and Hsp72 expression in leukocytes were measured before and after maximal exercise testing in 32 elderly persons (aged 73.2 years), who were assigned to two different groups depending on their level of physical activity during the past 12 months (OLow = moderate to low level; OHigh = higher level). RESULTS: The OHigh group showed higher aerobic fitness and TEAC (both representing 120% of OLow values) as well as lower oxidative damage (50% of OLow values) and Hsp72 expression. Exercise led to a lower increase in oxidative damage in the OHigh group. Aerobic fitness was positively correlated with TEAC and negatively with lipid peroxidation (TBARS). Hsp72 expression was negatively correlated with TEAC but positively correlated with TBARS levels. CONCLUSIONS: The key finding of this study is that, in people aged 60 to 90 years, long-term high level of physical activity preserved antioxidant capacity and limited oxidative damage accumulation. It also downregulated Hsp72 expression, an adaptation potentially resulting from lower levels of oxidative damage.

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.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.