Predictors of weight change in sedentary smokers receiving a standard smoking cessation intervention

L'arrêt de la cigarette est généralement associé à une prise de poids. Celle-ci peut menacer la motivation des fumeurs à s'engager dans un processus d'arrêt du tabac et constitue un motif de rechute. L'ordre de grandeur et la cinétique de la prise de poids liée à une tentative d'arrêt chez les fumeurs pris en charge selon les recommandations cliniques actuelles est peu décrite dans la littérature médicale. Le but de cette étude était de quantifier cette prise de poids, d'en déterminer la cinétique ainsi que les facteurs qui l'influencent, chez des fumeurs sédentaires bénéficiant d'une intervention d'aide à l'arrêt du tabac individualisée, composée de conseils individuels et d'une substitution nicotinique associant plusieurs modes d'administration. Nous avons analysé des données récoltées durant un essai clinique randomisé contrôlé au cours duquel était étudié l'impact d'une activité physique modérée sur les taux d'arrêt du tabac après un an chez des fumeurs sédentaires. Nous avons modélisé l'évolution du poids de l'ensemble des participants au cours du temps, selon la technique statistique des « modèles mixtes longitudinaux ». En séparant les périodes d'abstinence de la cigarette de celles de rechute et de l'utilisation reportée de substituts nicotiniques. Cette approche nous a permis de prendre en compte chaque participant à l'étude, par opposition à un modèle plus simple qui séparerait les sujets abstinents de ceux qui rechutent à n'importe quel moment de la période de suivi. Nous avons également ajusté ces modèles pour l'âge, le sexe, le niveau de dépendance à la nicotine et le niveau de formation des participants. Parmi l'ensemble des participants, nous avons noté une augmentation du poids durant les trois premiers mois de l'intervention, suivie d'une stabilisation. Au total, la prise de poids moyenne s'est élevée à 3.3 kg pour les femmes et 3.9 kg pour les hommes. Durant les périodes d'abstinence, les caractéristiques suivantes étaient associées à la prise de poids : sexe masculin et forte dépendance nicotinique. Un âge supérieur à 43 ans était associé à une prise de poids également durant les périodes de rechute. Nous avons observé une tendance, non statistiquement significative, vers une réduction de la prise des poids avec l'utilisation de substituts nicotiniques. Notre étude apporte de nouvelles données sur l'évolution du poids chez les fumeurs sédentaires qui bénéficient d'une intervention d'aide à l'arrêt du tabac. Ils prennent donc du poids, de manière modérée et limitée aux premiers mois. Parmi eux, les hommes, les individus les plus dépendants à la nicotine et les plus âgés doivent s'attendre à une prise de poids supérieure à la moyenne.

Application of standard and refined heat balance integral methods to one-dimensional Stefan problems

The work in this paper concerns the study of conventional and refined heat balance integral methods for a number of phase change problems. These include standard test problems, both with one and two phase changes, which have exact solutions to enable us to test the accuracy of the approximate solutions. We also consider situations where no analytical solution is available and compare these to numerical solutions. It is popular to use a quadratic profile as an approximation of the temperature, but we show that a cubic profile, seldom considered in the literature, is far more accurate in most circumstances. In addition, the refined integral method can give greater improvement still and we develop a variation on this method which turns out to be optimal in some cases. We assess which integral method is better for various problems, showing that it is largely dependent on the specified boundary conditions.

The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms.

Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferatoractivated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents.Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action.Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses.Results: DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment.Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds. Editor's SummaryDiethylhexyl phthalate (DEHP) is an industrial plasticizer used in cosmetics, medical devices, food packaging, and other applications. Evidence that DEHP metabolites can activate peroxisome proliferatoractivated receptors (PPARs) involved in fatty acid oxidation (PPARalpha and PPARbeta) and adiposite function and insulin resistance (PPARgamma) has raised concerns about potential effects of DEHP on metabolic homeostasis. In rodents, PPARalpha activation also induces hepatic peroxisome proliferation, but this response to PPARalpha activation is not observed in humans. Feige et al. (p. 234) evaluated systemic and metabolic consequences of high-dose oral DEHP in combination with a high-fat diet in wild-type mice and genetically engineered mouse PPAR models. The authors report that mice exposed to DEHP gained less weight than controls, without modifying their feeding behavior; they also exhibited lower triglyceride levels, smaller adipocytes, and improved glucose tolerance compared with controls. These effects, which were observed in mice fed both high-fat and standard diets, appeared to be mediated by PPARalpha-dependent activation of hepatic fatty acid catabolism without apparent involvement of PPARbeta or PPARgamma. However, mouse models that expressed human (versus mouse) PPARalpha tended to gain more weight on a high-fat diet than their DHEP-unexposed counterparts. The authors conclude that findings support species-specific metabolic effects of DEHP mediated by PPARalpha activation.

Diet diversity and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

Diet diversity (defined as the number of different foods consumed) has been considered an indicator of a healthy diet, and favorably related to the risk of several digestive tract cancers. We analyzed the relation between diet diversity and the risk of laryngeal cancer using data from a case-control study carried out between 1992 and 2000 in Italy and Switzerland. The subjects of the study were 527 patients with histologically confirmed incident cancers of the larynx and 1297 patients admitted for acute, non-neoplastic diseases, unrelated to tobacco or alcohol consumption. Total diversity was computed as the number of different foods (overall and within four food groups, i.e., vegetables, fruit, meat, and cereals) consumed at least once per week. A significant inverse association was observed for vegetable diversity (OR=0.41, 95% CI: 0.28-0.59, for the highest versus the lowest quartile) and fruit diversity (OR=0.40, 95% CI: 0.27-0.59). Conversely, a direct association was found for meat diversity (OR=1.67, 95% CI: 1.11-2.50), while no meaningful association was found for total diet and cereal diversity. The results were consistent across strata of age, alcohol drinking and tobacco smoking. This study suggests that a diet not only rich but also varied in fruit and vegetables is related to a decreased risk of laryngeal cancer risk.

Habitat, breeding performance, diet and individual age in Swiss barn owls (Tyto alba)

Intensification of farming over the past 50 years has homogenised the landscape structure and contributed to the decline of bird populations in Europe. To better target the conservation of the Barn Owl Tyto alba, we assessed the influence of the landscape structure on breeding performance in western Switzerland. The analyses considered a 23-year data set of breeding parameters collected in an area dominated by intensive agriculture. Using a Geographic Information System approach, landscape characteristics were described around 194 nest sites. Our analyses showed that nest-box occupancy, laying date, clutch and brood size, egg volume and probability of producing a second annual clutch were not significantly associated with any of the eight principal landscape variables (agricultural land, woodland, urban area, hedgerows, cereals, sugar beet, maize and meadow). Nevertheless, the probability that a breeding pair occupied a nest-box decreased the more roads there were surrounding the nest-box. The absence of strong associations between habitat features and breeding parameters suggests that prey availability may be relatively similar between the different breeding sites. In our study area Barn Owls can always find suitable foraging habitats around most nest-boxes.

Genetic and Antigenic Analysis of Adenovirus Type 3 Strains Showing Intermediate Behavior in Standard Seroneutralization Test

During an epidemiological survey of acute respiratory infection in Rio de Janeiro, among 208 adenovirus isolates, we found two strains that we were not able, by a standard neutralization procedure, to distinguish between type 3 or 7. However, DNA restriction pattern for the two strains with different enzymes were analyzed and showed a typical Ad3h profile. Using a cross-neutralization test in which both Ad3p and Ad7p antisera were used in different concentration against 100 TCID50 of each adenovirus standard and both isolates, we were able to confirm that the two isolates belong to serotype 3. An hemagglutination inhibition test also corroborated the identification of both strains as adenovirus type 3. Comparing Ad3h and Ad3p genome, we observed 16 different restriction enzyme sites, three of which were located in genomic regions encoding polypeptides involved in neutralization sites

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes.

BACKGROUND: In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial. PATIENTS AND METHODS: Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy, followed by pleuropneumonectomy and subsequent radiotherapy. QoL was assessed at baseline, at day 1 of cycle 3, and 1, 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist (RSCL) and the Schedule for the Evaluation of Quality of Life-Direct Weighting (SEIQoL-DW), a measure that is based on five individually nominated and weighted QoL-domains. RESULTS: Completion rates were 98% (RSCL) and 92% (SEIQoL) at baseline and 98%/89% at cycle 3, respectively. Of the operated patients (N=45) RSCL and SEIQoL were available from 86%/72%, 93%/74%, and 94%/76% at months 1, 3, and 6 post-surgery. Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL. Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinically significant deterioration (change>or=8 points) 1 month after surgery (median change of -66 and -14 for RSCL and SEIQoL, respectively). RSCL QoL overall scores improved thereafter, but remained beneath baseline level until 6 months after surgery. SEIQoL scores improved to baseline-level at month 3 after surgery, but worsened again at month 6. RSCL QoL overall score and SEIQoL index were moderately correlated at baseline (r=.30; p<or=.05) and at 6-month follow-up (r=.42; p<or=.05) but not at the other time points. CONCLUSION: The SEIQoL assessment seems to be feasible within a phase II clinical trial, but may require more effort from staff. More distinctive QoL changes in accordance with clinical changes were measured with the RSCL. Our findings suggest that the two measures are not interchangeable: the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest.

RTOG 0525: Exploratory Subset Analysis from a Randomized Phase III Trial Comparing Standard (std) Adjuvant Temozolomide (TMZ) with a Dose-dense (dd) Schedule for Glioblastoma (GBM)

Purpose/Objective(s): RTwith TMZ is the standard for GBM. dd TMZ causes prolongedMGMTdepletion in mononuclear cells and possibly in tumor. The RTOG 0525 trial (ASCO 2011) did not show an advantage from dd TMZ for survival or progression free survival. We conducted exploratory, hypothesis-generating subset analyses to detect possible benefit from dd TMZ.Materials/Methods: Patients were randomized to std (150-200 mg/m2 x 5 d) or dd TMZ (75-100 mg/m2 x 21 d) q 4 weeks for 6- 12 cycles. Eligibility included age.18, KPS$ 60, and. 1 cm2 tissue for prospective MGMTanalysis for stratification. Furtheranalyses were performed for all randomized patients (''intent-to-treat'', ITT), and for all patients starting protocol therapy (SPT). Subset analyses were performed by RPA class (III, IV, V), KPS (90-100, = 50,\50), resection (partial, total), gender (female, male), and neurologic dysfunction (nf = none, minor, moderate).Results: No significant difference was seen for median OS (16.6 vs. 14.9 months), or PFS (5.5 vs. 6.7 months, p = 0.06). MGMT methylation was linked to improved OS (21.2 vs. 14 months, p\0.0001), and PFS (8.7 vs. 5.7 months, p\0.0001). For the ITT (n = 833), there was no OS benefit from dd TMZ in any subset. Two subsets showed a PFS benefit for dd TMZ: RPA class III (6.2 vs. 12.6 months, HR 0.69, p = 0.03) and nf = minor (HR 0.77, p = 0.01). For RPA III, dd dramatically delayed progression, but post-progression dd patients died more quickly than std. A similar pattern for nf = minor was observed. For the SPT group (n = 714) there was neither PFS nor OS benefit for dd TMZ, overall. For RPA class III and nf = minor, there was a PFS benefit for dd TMZ (HR 0.73, p = 0.08; HR 0.77, p = 0.02). For nf = moderate subset, both ITT and SPT, the std arm showed superior OS (14.4 vs. 10.9 months) compared to dd, without improved PFS (HR 1.46, p = 0.03; and HR 1.74, p = 0.01. In terms of methylation status within this subset, there were more methylated patients in the std arm of the ITT subset (n = 159; 32 vs. 24%). For the SPT subset (n = 124), methylation status was similar between arms.Conclusions: This study did not demonstrate improved OS for dd TMZ for any subgroup, but for 2 highly functional subgroups, PFS was significantly increased. These data generate the testable hypothesis that intensive treatment may selectively improve disease control in those most likely able to tolerate dd therapy. Interpretation of this should be considered carefully due to small sample size, the process of multiple observations, and other confounders.Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI).

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

Effect of Sodium Loading/Depletion on Renal Oxygenation in Young Normo-and Hypertensive Men Measured with BOLD-MRI

Objective: To measure renal tissue oxygenation in young normo-and hypertensive volunteers under conditions of salt loading and depletion using blood oxygen level dependent magnetic resonance imaging (BOLD-MRI). Design and Methods: Ten normotensive (NT) male volunteers (age 26.5_7.4 y) and eight non-treated, hypertensive (HT) male volunteers (age 28.8_5.7 y) were studied after one week on a high salt (HS) regimen (6g of salt/day added to their normal regimen) and again after one week of a low sodium diet (LS). On the 8th day, BOLD-MRI was performed under standard hydration conditions. Four coronal slices were selected in each kidney, and combination sequence was used to acquire T2* weighted images. The mean R2* (1/T2*) was measured to determine cortical and medullar oxygenation. Results: Baseline characteristics and their changes are shown in the table. The mean cortical R2* was not different under conditions of HS or LS (17.8_1.3 vs. 18.2_0.6 respectively in NT group, p_0.27; 17.4_0.6 vs 17.8_0.9 in HT group, p_0.16). However, the mean medullary R2* was significantly lower under LS conditions in both groups (31.3_0.6 vs 28.1_0.8 in NT group, p_0.05; 30.3_0.8 vs 27.9_1.5 in HT group, p_0.05), corresponding to higher medullary oxygenation as compared to HS conditions, without significant changes in hemoglobin or hematocrit values. The salt induced changes in medullary oxygenation were comparable in the two groups (ANOVA, p_0.1). Conclusion: Dietary sodium restriction leads to increased renal medullary oxygenation compared to high sodium intake in normo-and hypertensive subjects. This observation may in part explain the potential renal benefits of a low sodium intake.

How to use the standard model with own data?

In this work discuss the use of the standard model for the calculation of the solvency capital requirement (SCR) when the company aims to use the specific parameters of the model on the basis of the experience of its portfolio. In particular, this analysis focuses on the formula presented in the latest quantitative impact study (2010 CEIOPS) for non-life underwriting premium and reserve risk. One of the keys of the standard model for premium and reserves risk is the correlation matrix between lines of business. In this work we present how the correlation matrix between lines of business could be estimated from a quantitative perspective, as well as the possibility of using a credibility model for the estimation of the matrix of correlation between lines of business that merge qualitative and quantitative perspective.

Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?

Objective Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.Methods We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks.Results All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero.Conclusion The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system. J Hypertens 29: 2454-2461 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.