Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents.

CONTEXT: Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children. OBJECTIVE: To examine the independent and combined associations between objectively measured time in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time with cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from 14 studies between 1998 and 2009 comprising 20 871 children (aged 4-18 years) from the International Children's Accelerometry Database. Time spent in MVPA and sedentary time were measured using accelerometry after reanalyzing raw data. The independent associations between time in MVPA and sedentary time, with outcomes, were examined using meta-analysis. Participants were stratified by tertiles of MVPA and sedentary time. MAIN OUTCOME MEASURES: Waist circumference, systolic blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and insulin. RESULTS: Times (mean [SD] min/d) accumulated by children in MVPA and being sedentary were 30 (21) and 354 (96), respectively. Time in MVPA was significantly associated with all cardiometabolic outcomes independent of sex, age, monitor wear time, time spent sedentary, and waist circumference (when not the outcome). Sedentary time was not associated with any outcome independent of time in MVPA. In the combined analyses, higher levels of MVPA were associated with better cardiometabolic risk factors across tertiles of sedentary time. The differences in outcomes between higher and lower MVPA were greater with lower sedentary time. Mean differences in waist circumference between the bottom and top tertiles of MVPA were 5.6 cm (95% CI, 4.8-6.4 cm) for high sedentary time and 3.6 cm (95% CI, 2.8-4.3 cm) for low sedentary time. Mean differences in systolic blood pressure for high and low sedentary time were 0.7 mm Hg (95% CI, -0.07 to 1.6) and 2.5 mm Hg (95% CI, 1.7-3.3), and for high-density lipoprotein cholesterol, differences were -2.6 mg/dL (95% CI, -1.4 to -3.9) and -4.5 mg/dL (95% CI, -3.3 to -5.6), respectively. Geometric mean differences for insulin and triglycerides showed similar variation. Those in the top tertile of MVPA accumulated more than 35 minutes per day in this intensity level compared with fewer than 18 minutes per day for those in the bottom tertile. In prospective analyses (N = 6413 at 2.1 years' follow-up), MVPA and sedentary time were not associated with waist circumference at follow-up, but a higher waist circumference at baseline was associated with higher amounts of sedentary time at follow-up. CONCLUSION: Higher MVPA time by children and adolescents was associated with better cardiometabolic risk factors regardless of the amount of sedentary time.

Retinal thickening in HLA-B27 associated acute anterior uveitis: evolution with time and association with severity of inflammatory activity.

Purpose: To describe the evolution of retinal thickness in eyes affected with acute anterior uveitis (AAU) in the course of follow-up and to assess its correlation with severity of inflammatory activity in the anterior chamber. Methods: Design: Prospective, cohort study Setting: Institutional study Patient population: 72 eyes (affected and fellow eyes) of 36 patients Observation procedure: Patients were followed daily until beginning of resolution of inflammatory activity and weekly thereafter. Optical coherence tomography and laser flare photometry were performed at each visit. Treatment consisted of topical corticosteroids Main outcome measures: Retinal thickness of affected eyes, difference in retinal thickness between affected and fellow eyes and their evolution in time, association between maximal retinal thickness and initial laser flare photometry. Results: Difference in retinal thickness between affected and fellow eyes became significant on average seven days from baseline and remained so through-out follow-up (p<0.001). There was a steep increase in retinal thickness of affected eyes followed by a progressive decrease after reaching a peak value. Maximal difference in retinal thickness between affected and fellow eyes was observed between 17 and 25 days from baseline and exhibited a strong, positive correlation with initial laser flare photometry values (p=0.015). Conclusions: Retinal thickness in eyes affected with AAU presents a steep increase over 3 to 4 weeks and then gradually decreases. Severity of inflammation at baseline predicts the amount of retinal thickening in affected eyes. A characteristic pattern of temporal response of retinal anatomy to inflammatory stimuli seems to arise.

Neoadjuvant and adjuvant strategies in renal cell carcinoma: more questions than answers.

The current standard treatment for early stage (I-III) renal cell cancer (RCC) is surgery. While the prognosis of stage I tumors is excellent, stage II and particularly stage III have a high risk of relapse. The adjuvant treatment of patients with RCC remains an area of investigation, with patient selection being a key aspect. There are currently two prognostic nomograms to establish the risk of relapse in patients with resected RCC. The results of earlier studies of adjuvant therapy, including the use chemotherapy and/or immunotherapy after nephrectomy have failed to show any benefit in the outcome of patients at risk of developing local recurrence or distant metastases. Two recent phase III trials with vaccines (autologous tumor cell vaccine and autologous tumor-derived heat shock protein peptide complex-96) have shown promising, albeit still preliminary, results. In the metastatic RCC setting, recent advances in the molecular understanding of oncogenic pathways have led to the development of new therapeutic strategies with the use of targeted therapies in the adjuvant setting. Neoadjuvant treatment is another treatment modality currently being evaluated for patients with early disease and in patients with metastatic RCC with inoperable primary tumors. The questions that remain unanswered include activity of these agents in early stages of the disease, patient selection, optimal start time of the adjuvant treatment, and finally, the optimal length of treatment.

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study.

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients were included who had genotypic resistance tests performed on plasma samples collected while antiretroviral therapy naive. TDR was defined as at least one resistance mutation from a list proposed for genotypic TDR surveillance. Multivariable logistic regression was used to analyze factors associated with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients with resistance and consequently low power.

Increasing prevalence of obesity in the Seychelles and association with socioeconomic status

Objective: We assessed the 15-year trends in the distribution of body mass index (BMI) categories in the Seychelles (Indian Ocean, African Region) and the relationship with sex, age and socio-economic status (SES). Methods: We conducted three population-based examination surveys in 1989 (n=1,081; participation rate: 86.4%), in 1994 (n=1,067; 87.0%), and in 2004 (n=1,255; 80.2%). Occupation was categorized as "laborer", "intermediate" or "professional". Results are adjusted to the population of 2002. Results: Between 1989 and 2004, mean BMI increased markedly in all sex and age categories (overall: ∼0.15 kg/m2/calendar year). The prevalence of overweight and obesity combined ("excess weight", BMI ≥25 kg/m2) increased from 29% to 52% in men and from 50% to 67% in women. The prevalence of obesity (BMI ≥30 kg/m2) increased from 4% to 15% in men and from 23% to 34% in women. Mean BMI - respectively the prevalence of excess weight- was lower in laborers than professionals in men but higher in laborers that professionals in women and this pattern was similar in the three surveys. Odds ratios for excess weight in professionals vs. laborers were 2.10 (95% CI: 1.94-2.17) in men and 0.51 (0.48-0.53) in women, adjusting for calendar year and participants' age and smoking habits. Conclusion: The prevalence of overweight/obesity increased markedly during a 15- year period. Similar increase of BMI over time in all age and sex categories suggests common environment obesogenic factors. The association between SES and excess weight was in opposite directions in men and women. The study emphasizes the need for prevention measures in all sex, age and SES groups, and suggests that they should be tailored according to sex and SES categories.

Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.

Resistance to alkylating agents via direct DNA repair by O(6)-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O(6)-benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.

Exercice physique et artériopathie oblitérante des membres inférieurs [Physical activity and peripheral arterial obstructive disease]

Intermittent claudication (IC) is the most common clinical manifestation of atherosclerotic peripheral arterial disease. Exercise training plays a major role in treating patients with IC. Regular exercise increases functional walking capacity, reduces cardiovascular mortality and improves quality of life. This seems to be achieved by: favorable effect on cardiovascular risk factors, anti-inflammatory effect, increased collateral blood flux, improved rheology profile, endothelial function, fibrinolysis, and muscular metabolism. However, exact mechanisms underlying beneficial effect of exercise remain largely unknown. Exercise modalities will be discussed in this article.

Relationship between physical inactivity and adiposity in prepubertal boys.

OBJECTIVE: To study the relationship between the energy expenditure for activity (EEAct), the level of activity and adiposity in a group of 9-year-old boys (n = 28) with different body composition (body weight, 38 +/- 10 kg [range, 23 to 66 kg]; fat mass, 23% +/- 10% [range, 8% to 42%]). METHODS: Total energy expenditure (TEE) was measured by means of the heart-rate monitoring method. EEAct was calculated as TEE-(REE+0.1 TEE), where REE is the postabsorptive resting energy expenditure and 0.1 TEE corresponds to the postprandial thermogenesis (approximately 10% of TEE). RESULTS: TEE, REE, and EEAct were 9388 +/- 1859, 5154 +/- 642, and 3295 +/- 1356 l J/day, respectively. Daily time devoted to sedentary and nonsedentary activities averaged 290 +/- 155 minutes (range, 69 to 621) and 534 +/- 150 minutes (range, 180 to 783), respectively. Time spent on sedentary activities was directly proportional to fat mass percentage (r = 0.46; p < 0.05). It was the only variable, among the free-living physical-activity [EEAct, TEE/(REE+0.1 TEE) ratio, time spent in nonsedentary and sedentary activities] variables, which remained significantly in the multiple step-down regression analysis final equation (r = 0.46; p < 0.05). CONCLUSIONS: The positive relationship between adiposity and time spent on sedentary activities in 9-year-old boys suggests the importance of the role played by muscular activity, at least in the maintenance of obesity in childhood. Prepubertal children should be encouraged to spend less time on sedentary activities to treat and prevent their obesity.

Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

Context: Sarcopenia is thought to be associated with mitochondrial (M) loss. It is unclear whether the decrease in M content is consequent to aging per se or to decreased physical activity. Objectives: To examine the influence of fitness on M content and function, and to assess whether exercise could improve M function in older adults. Design and subjects: Three distinct studies were conducted: 1) a cross-sectional observation comparing M content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults (A) and sedentary (S) subjects matched for age and gender; 3) a 4-month exercise intervention in S. Setting: University-based clinical research center Outcomes: M volume density (Mv) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins (ETC) by western blotting, mRNAs for transcription factors involved in M biogenesis by qRT-PCR and in-vivo oxidative capacity (ATPmax) by (31)P-MR spectroscopy. Peak oxygen uptake (VO2peak) was measured by GXT. Results: VO2peak was strongly correlated with Mv in eighty 60-80 yo adults. Comparison of A vs. S revealed differences in Mv, ATPmax and some ETC complexes. Finally, exercise intervention confirmed that S are able to recover Mv, ATPmax and specific transcription factors. Conclusions: These data suggest that 1) aging per se is not the primary culprit leading to M dysfunction, 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle M content and may prevent aging muscle comorbidities and 3) the improvement of M function is all about content.

Employment risk, unemployment insurance and search strategies: a disaggregated equilibrium approach with application to the Swiss labour market in the 1990-ies

The Organization of the Thesis The remainder of the thesis comprises five chapters and a conclusion. The next chapter formalizes the envisioned theory into a tractable model. Section 2.2 presents a formal description of the model economy: the individual heterogeneity, the individual objective, the UI setting, the population dynamics and the equilibrium. The welfare and efficiency criteria for qualifying various equilibrium outcomes are proposed in section 2.3. The fourth section shows how the model-generated information can be computed. Chapter 3 transposes the model from chapter 2 in conditions that enable its use in the analysis of individual labor market strategies and their implications for the labor market equilibrium. In section 3.2 the Swiss labor market data sets, stylized facts, and the UI system are presented. The third section outlines and motivates the parameterization method. In section 3.4 the model's replication ability is evaluated and some aspects of the parameter choice are discussed. Numerical solution issues can be found in the appendix. Chapter 4 examines the determinants of search-strategic behavior in the model economy and its implications for the labor market aggregates. In section 4.2, the unemployment duration distribution is examined and related to search strategies. Section 4.3 shows how the search- strategic behavior is influenced by the UI eligibility and section 4.4 how it is determined by individual heterogeneity. The composition effects generated by search strategies in labor market aggregates are examined in section 4.5. The last section evaluates the model's replication of empirical unemployment escape frequencies reported in Sheldon [67]. Chapter 5 applies the model economy to examine the effects on the labor market equilibrium of shocks to the labor market risk structure, to the deep underlying labor market structure and to the UI setting. Section 5.2 examines the effects of the labor market risk structure on the labor market equilibrium and the labor market strategic behavior. The effects of alterations in the labor market deep economic structural parameters, i.e. individual preferences and production technology, are shown in Section 5.3. Finally, the UI setting impacts on the labor market are studied in Section 5.4. This section also evaluates the role of the UI authority monitoring and the differences in the Way changes in the replacement rate and the UI benefit duration affect the labor market. In chapter 6 the model economy is applied in counterfactual experiments to assess several aspects of the Swiss labor market movements in the nineties. Section 6.2 examines the two equilibria characterizing the Swiss labor market in the nineties, the " growth" equilibrium with a "moderate" UI regime and the "recession" equilibrium with a more "generous" UI. Section 6.3 evaluates the isolated effects of the structural shocks, while the isolated effects of the UI reforms are analyzed in section 6.4. Particular dimensions of the UI reforms, the duration, replacement rate and the tax rate effects, are studied in section 6.5, while labor market equilibria without benefits are evaluated in section 6.6. In section 6.7 the structural and institutional interactions that may act as unemployment amplifiers are discussed in view of the obtained results. A welfare analysis based on individual welfare in different structural and UI settings is presented in the eighth section. Finally, the results are related to more favorable unemployment trends after 1997. The conclusion evaluates the features embodied in the model economy with respect to the resulting model dynamics to derive lessons from the model design." The thesis ends by proposing guidelines for future improvements of the model and directions for further research.