Effect of a 1-hour single bout of moderate-intensity exercise on fat oxidation kinetics.

The present study aimed to examine the effects of a prior 1-hour continuous exercise bout (CONT) at an intensity (Fat(max)) that elicits the maximal fat oxidation (MFO) on the fat oxidation kinetics during a subsequent submaximal incremental test (IncrC). Twenty moderately trained subjects (9 men and 11 women) performed a graded test on a treadmill (Incr), with 3-minute stages and 1-km.h(-1) increments. Fat oxidation was measured using indirect calorimetry and plotted as a function of exercise intensity. A mathematical model (SIN) including 3 independent variables (dilatation, symmetry, and translation) was used to characterize the shape of fat oxidation kinetics and to determine Fat(max) and MFO. On a second visit, the subjects performed CONT at Fat(max) followed by IncrC. After CONT performed at 57% +/- 3% (means +/- SE) maximal oxygen uptake (Vo(2max)), the respiratory exchange ratio during IncrC was lower at every stage compared with Incr (P < .05). Fat(max) (56.4% +/- 2.3% vs 51.5% +/- 2.4% Vo(2max), P = .013), MFO (0.50 +/- 0.03 vs 0.40 +/- 0.03 g.min(-1), P < .001), and fat oxidation rates from 35% to 70% Vo(2max) (P < .05) were significantly greater during IncrC compared with Incr. However, dilatation and translation were not significantly different (P > .05), whereas symmetry tended to be greater in IncrC (P = .096). This study showed that the prior 1-hour continuous moderate-intensity exercise bout increased Fat(max), MFO, and fat oxidation rates over a wide range of intensities during the postexercise incremental test. Moreover, the shape of the postexercise fat oxidation kinetics tended to have a rightward asymmetry.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Materials and methods: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Effects of high-intensity exercises on 13C-nandrolone excretion in trained athletes.

OBJECTIVE: Nandrolone is an anabolic steroid widely used in several sports. The numerous nandrolone positive cases in the recent years (International Olympic Committee statistics) led to several studies in the antidoping field. Nevertheless, essential questions pertaining to nandrolone endogenous production, the effects of physical exercise on the excretion of nandrolone metabolites, and contamination from nutritional supplements must still be addressed. The purpose of this study was to evaluate the influence of exhaustive exercises on 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) urinary excretion rates after administration of labeled nandrolone. SETTING AND PARTICIPANTS: A total of 34 healthy male Caucasian volunteers from the Institute of Sports Sciences and Physical Education (University of Lausanne) applied to participate in the study. All subjects were free from any physical drug addiction and were instructed strictly to avoid any nutritional supplement or steroid before and during the study. The participants were randomly dispatched in 2 groups in a double-blind way: a placebo group and a group treated with C-labeled nandrolone. MAIN OUTCOME MEASUREMENTS: The urinary concentrations of the 2 main nandrolone metabolites, 19-NA and 19-NE, were measured using gas chromatography coupled with mass spectrometry. In addition, clinical parameters such as creatinine, total protein, and beta2-microglobuline levels were determined using immunologic assays. RESULTS: After an oral ingestion of a 25 mg 3,4-C2-nandrolone dose, followed by a second identical dose 24 hours later, 19-NA and 19-NE could be detected in the urine for a period of 6 days after the initial intake. Despite several interesting observations, the measurements were very scattered and did not appear to be significantly influenced by exercise sessions in the athlete population. CONCLUSIONS: The results of this study suggest that physical exercise cannot be considered as a reliable parameter that systematically affects nandrolone metabolite concentrations in the urine.

Differences in low-grade chronic inflammation and insulin resistance in women with previous gestational diabetes mellitus and women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are both characterized by an increase in insulin resistance. Our goal in the present study was to measure insulin resistance (as estimated by homeostasis model assessment, sex hormone-binding globulin (SHBG) and adiponectin concentrations) and parameters of low-grade inflammation in non-diabetic, non-hyperandrogenic ovulatory women with previous GDM (pGDM) and in non-diabetic women with classic PCOS, characterized by hyperandrogenism and oligo/anovulation. PATIENTS AND DESIGN: We evaluated 20 women with PCOS, 18 women with pGDM and 19 controls, all matched according to body mass index (BMI). Fasting blood samples were drawn in all women 3-6 days after spontaneous or dydrogesterone-induced withdrawal bleeding. Body fat distribution was assessed using dual-energy X-ray absorptiometry in all women. RESULTS: After adjusting for age and percent body fat, measures of insulin resistance such as SHBG and adiponectin concentrations were decreased and central obesity was increased in women with PCOS and pGDM compared with controls (all p < 0.05). Parameters of low-grade inflammation such as serum tumor necrosis factor-alpha and highly sensitive C-reactive protein concentrations, white blood cell and neutrophil count were increased only in women with PCOS compared with BMI-matched controls (all p < 0.05). CONCLUSIONS: Certain markers of insulin resistance are increased in both women with PCOS and women with pGDM, while low-grade inflammation is increased only in PCOS. PCOS and GDM might represent specific phenotypes of one disease entity with an increased risk of cardiovascular disease, whereby women with PCOS demonstrate an augmented cardiovascular risk profile.

Transscleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels.

The major problems associated with the use of corticosteroids for the treatment of ocular diseases are their poor intraocular penetration to the posterior segment when administered locally and their secondary side effects when given systemically. To circumvent these problems more efficient methods and techniques of local delivery are being developed. The purposes of this study were: (1) to investigate the pharmacokinetics of intraocular penetration of hemisuccinate methyl prednisolone (HMP) after its delivery using the transscleral Coulomb controlled iontophoresis (CCI) system applied to the eye or after intravenous (i.v.) injection in the rabbit, (2) to test the safety of the CCI system for the treated eyes and (3) to compare the pharmacokinetic profiles of HMP intraocular distribution after CCI delivery to i.v. injection. For each parameter evaluated, six rabbit eyes were used. For the CCI system, two concentrations of HMP (62.5 and 150mg ml(-1)), various intensities of current and duration of treatment were analyzed. In rabbits serving as controls the HMP was infused in the CCI device but without applied electric current. For the i.v. delivery, HMP at 10mg kg(-1)as a 62.5mg ml(-1)solution was used. The rabbits were observed clinically for evidence of ocular toxicity. At various time points after the administration of drug, rabbits were killed and intraocular fluids and tissues were sampled for methylprednisolone (MP) concentrations by high pressure liquid chromatography (HPLC). Histology examinations were performed on six eyes of each group. Among groups that received CCI, the concentrations of MP increased in all ocular tissues and fluids in relation to the intensities of current used (0.4, 1.0 and 2.0mA/0.5cm(2)) and its duration (4 and 10min). Sustained and highest levels of MP were achieved in the choroid and the retina of rabbit eyes treated with the highest current and 10min duration of CCI. No clinical toxicity or histological lesions were observed following CCI. Negligible amounts of MP were found in ocular tissues in the CCI control group without application of current. Compared to i.v. administration, CCI achieved higher and more sustained tissue concentrations with negligible systemic absorption. These data demonstrate that high levels of MP can be safely achieved in intraocular tissues and fluids of the rabbit eye, using CCI. With this system, intraocular tissues levels of MP are higher than those achieved after i.v. injection. Furthermore, if needed, the drug levels achieved with CCI can be modulated as a function of current intensity and duration of treatment. CCI could therefore be used as an alternative method for the delivery of high levels of MP to the intraocular tissues of both the anterior and posterior segments.

Differential expression of NLRP3 among hematopoietic cells.

Although the importance of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in health and disease is well appreciated, a precise characterization of NLRP3 expression is yet undetermined. To this purpose, we generated a knock-in mouse in which the Nlrp3 coding sequence was substituted for the GFP (enhanced GFP [egfp]) gene. In this way, the expression of eGFP is driven by the endogenous regulatory elements of the Nlrp3 gene. In this study, we show that eGFP expression indeed mirrors that of NLRP3. Interestingly, splenic neutrophils, macrophages, and, in particular, monocytes and conventional dendritic cells showed robust eGFP fluorescence, whereas lymphoid subsets, eosinophils, and plasmacytoid dendritic cells showed negligible eGFP levels. NLRP3 expression was highly inducible in macrophages, both by MyD88- and Trif-dependent pathways. In vivo, when mice were challenged with diverse inflammatory stimuli, differences in both the number of eGFP-expressing cells and fluorescence intensity were observed in the draining lymph node. Thus, NLRP3 levels at the site of adaptive response initiation are controlled by recruitment of NLRP3-expressing cells and by NLRP3 induction.

The effect of muscle fatigue on stimulus intensity requirements for central and peripheral fatigue quantification.

PURPOSE: The present study was designed to determine the stimulation intensity necessary for an adequate assessment of central and peripheral components of neuromuscular fatigue of the knee extensors. METHODS: Three different stimulation intensities (100, 120 and 150 % of the lowest intensity evoking a plateau in M-waves and twitch amplitudes, optimal stimulation intensity, OSI) were used to assess voluntary activation level (VAL) as well as M-wave, twitch and doublet amplitudes before, during and after an incremental isometric exercise performed by 14 (8 men) healthy and physically active volunteers. A visual analog scale was used to evaluate the associated discomfort. RESULTS: There was no difference (p > 0.05) in VAL between the three intensities before and after exercise. However, we found that stimulating at 100 % OSI may overestimate the extent of peripheral fatigue during exercise, whereas 150 % OSI stimulations led to greater discomfort associated with doublet stimulations as well as to an increased antagonist co-activation compared to 100 % OSI. CONCLUSION: We recommend using 120 % OSI, as it constitutes a good trade-off between discomfort and reliable measurements.

A new measurement of energy expenditure and physical activity in patients treated by maintenance hemodialysis

Purpose: The accurate estimation of total energy expenditure (TEE) is essential to allow the provision of nutritional requirements in patients treated by maintenance hemodialysis (MHD). The measurement of TEE and resting energy expenditure (REE) by direct or indirect calorimetry and doubly labeled water are complicated, timeconsuming and cumbersome in this population. Recently, a new system called SenseWear® armband (SWA) was developed to assess TEE, physical activity and REE. This device works by measurements of body acceleration in two axes, heat production and steps counts. REE measured by indirect calorimetry and SWA are well correlated. The aim of this study was to determine TEE, physical activity and REE on patients on MHD using this new device. Methods and materials: Daily TEE, REE, step count, activity time, intensity of activity and lying time were determined for 7 consecutive days in unselected stable patients on MHD and sex, age and weightmatched healthy controls (HC). Patients with malnutrition, cancer, use of immunosuppressive drugs, hypoalbumemia <35 g/L and those hospitalized in the last 3 months, were excluded. For MHD patients, separate analyses were conducted in dialysis and non-dialysis days. Relevant parameters known to affect REE, such as BMI, albumin, pre-albumin, hemoglobin, Kt/V, CRP, bicarbonate, PTH, TSH, were recorded. Results: Thirty patients on MHD and 30 HC were included. In MHD patients, there were 20 men and 10 women. Age was 60,13 years ± 14.97 (mean ± SD), BMI was 25.77 kg/m² ± 4.73 and body weight was 74.65 kg ± 16.16. There were no significant differences between the two groups. TEE was lower in MHD patients compared to HC (28.79 ± 5.51 SD versus 32.91 ± 5.75 SD kcal/kg/day; p <0.01). Activity time was significantly lower in patients on MHD (101.3 ± 12.6SD versus 50.7 ± 9.4 SD min; p = 0.0021). Energy expenditure during the time of activity was significantly lower in MHD patients. MHD patients walked 4543 ± 643 SD vs 8537 ± 744 SD steps per day (p <0.0001). Age was negatively correlated with TEE (r = -0.70) and intensity of activity (r = -0.61) in HC, but not in patients on MHD. TEE showed no difference between dialysis and non-dialysis days (29.92 ± 2.03 SD versus 28.44 ± 1.90 SD kcal/kg/day; p = NS), reflecting a lack of difference in activity (number of steps, time of physical activity) and REE. This finding was observed in MHD patients both older and younger than 60 years. However, age stratification appeared to have an influence on TEE, regardless of dialysis day, (29.92 ± 2.07 SD kcal/kg/day for <60 years-old versus 27.41 ± 1.04 SD kcal/kg/day for ≥60 years old), although failing to reach statistical significance. Conclusion: Using SWA, we have shown that stable patients on MHD have a lower TEE than matched HC. On average, a TEE of 28.79 kcal/kg/day, partially affected by age, was measured. This finding gives support to the clinical impression that it is difficult and probably unnecessary to provide an energy amount of 30-35 kcal/kg/day, as proposed by international guidelines for this population. In addition, we documented for the first time that MHD patients exert a reduced physical activity as compared to HC. There were surprisingly no differences in TEE, REE and physical activity parameters between dialysis and non-dialysis days. This observation might be due to the fact that patients on MHD produce a physical effort to reach the dialysis centre. Age per se did not influence physical activity in MHD patients, contrary to HC, reflecting the impact of co-morbidities on physical activity in this group of patients.

High b-value Diffusion-weighted Imaging: A Sensitive Method to Reveal White Matter Changes in Schizophrenia

Background: b-value is the parameter characterizing the intensity of the diffusion weighting during image acquisition. Data acquisition is usually performed with low b value (b~1000 s/mm2). Evidence shows that high b-values (b>2000 s/mm2) are more sensitive to the slow diffusion compartment (SDC) and maybe more sensitive in detecting white matter (WM) anomalies in schizophrenia.Methods: 12 male patients with schizophrenia (mean age 35 +/-3 years) and 16 healthy male controls matched for age were scanned with a low b-value (1000 s/mm2) and a high b-value (4000 s/mm2) protocol. Apparent diffusion coefficient (ADC) is a measure of the average diffusion distance of water molecules per time unit (mm2/s). ADC maps were generated for all individuals. 8 region of interests (frontal and parietal region bilaterally, centrum semi-ovale bilaterally and anterior and posterior corpus callosum) were manually traced blind to diagnosis.Results: ADC measures acquired with high b-value imaging were more sensitive in detecting differences between schizophrenia patients and healthy controls than low b-value imaging with a gain in significance by a factor of 20- 100 times despite the lower image Signal-to-noise ratio (SNR). Increased ADC was identified in patient's WM (p=0.00015) with major contributions from left and right centrum semi-ovale and to a lesser extent right parietal region.Conclusions: Our results may be related to the sensitivity of high b-value imaging to the SDC believed to reflect mainly the intra-axonal and myelin bound water pool. High b-value imaging might be more sensitive and specific to WM anomalies in schizophrenia than low b-value imaging

Light intensity modulates the regulatory network of the shade avoidance response in Arabidopsis.

Plants such as Arabidopsis thaliana respond to foliar shade and neighbors who may become competitors for light resources by elongation growth to secure access to unfiltered sunlight. Challenges faced during this shade avoidance response (SAR) are different under a light-absorbing canopy and during neighbor detection where light remains abundant. In both situations, elongation growth depends on auxin and transcription factors of the phytochrome interacting factor (PIF) class. Using a computational modeling approach to study the SAR regulatory network, we identify and experimentally validate a previously unidentified role for long hypocotyl in far red 1, a negative regulator of the PIFs. Moreover, we find that during neighbor detection, growth is promoted primarily by the production of auxin. In contrast, in true shade, the system operates with less auxin but with an increased sensitivity to the hormonal signal. Our data suggest that this latter signal is less robust, which may reflect a cost-to-robustness tradeoff, a system trait long recognized by engineers and forming the basis of information theory.

International differences in alcohol use according to sexual orientation.

Most research on sexual orientation and alcohol use in the United States has found higher rates of alcohol use and abuse among gay men and lesbians. Studies from other countries have found smaller or no differences between sexual minority and heterosexual women and men. The present study used general population survey data from 14 countries to examine high-volume and risky single-occasion drinking by sexual orientation. Data from 248 gay men and lesbians and 3720 heterosexuals were analyzed in a case-control design. In several countries partnered or recently partnered gay men and lesbians had no greater risk of heavy drinking or engaging in heavy drinking than heterosexual controls. Only lesbians in North America showed higher risk for both indicators. Future general population health research should include larger samples of gays and lesbians and use more comprehensive measures of sexual orientation for investigating the prevalence of health risk factors.

School burnout in adolescents : Differences in background variables and exploration of school-related stress at the end of compulsory schooling

The aim of this study is to contribute to a better understanding of the risk factors associated with school burnout, which has recently been described as a syndrome of emotional exhaustion due to school demands, cynical and detached attitude towards school and feelings of inadequacy as a student (Salmela-Aro, Kiuru, Pietikainen & Jokela, 2008a). The research focuses on students in the last years of compulsory schooling, period in which burnout has not received much attention yet. A total of 342 adolescents (Mean age = 14.84) were asked to complete questionnaires about school burnout, school-related stress and background variables. The results showed differences in school burnout by gender, grade level and school track, with girls, last grade of compulsory school and high-track classes, showing the highest scores. No difference was observed with respect to grade retention. Several types of school stress were identified, with stress type Success related to pressures to succeed and concerns about the academic future being the highest. Finally, stress and burnout were strongly and positively correlated, and the type of stress Success was the best predictor of overall Burnout, Exhaustion and Inadequacy dimension scores. The results are discussed in relation to their theoretical relevance and implications for the prevention of school burnout in adolescents.