Changes in running mechanics and spring-mass behaviour during a 5-km time trial.

Research into the biomechanical manifestation of fatigue during exhaustive runs is increasingly popular but additional understanding of the adaptation of the spring-mass behaviour during the course of strenuous, self-paced exercises continues to be a challenge in order to develop optimized training and injury prevention programs. This study investigated continuous changes in running mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes performed a 5-km running time trial (mean performance: ̴17 min 30 s) on a 200 m indoor track. Vertical and anterior-posterior ground reaction forces were measured every 200 m by a 5-m long force platform system, and used to determine spring-mass model characteristics. After a fast start, running velocity progressively decreased (- 11.6%; P<0.001) in the middle part of the race before an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+ 8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%; P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring-mass behaviour progressively changes during a 5-km time trial towards deteriorated vertical stiffness, which alters impact and force production characteristics.

Ink dating using thermal desorption and gas chromatography / mass spectrometry: comparison of results obtained in two laboratories

Recent ink dating methods focused mainly on changes in solvent amounts occurring over time. A promising method was developed at the Landeskriminalamt of Munich using thermal desorption (TD) followed by gas chromatography / mass spectrometry (GC/MS) analysis. Sequential extractions of the phenoxyethanol present in ballpoint pen ink entries were carried out at two different temperatures. This method is applied in forensic practice and is currently implemented in several laboratories participating to the InCID group (International Collaboration on Ink Dating). However, harmonization of the method between the laboratories proved to be a particularly sensitive and time consuming task. The main aim of this work was therefore to implement the TD-GC/MS method at the Bundeskriminalamt (Wiesbaden, Germany) in order to evaluate if results were comparable to those obtained in Munich. At first validation criteria such as limits of reliable measurements, linearity and repeatability were determined. Samples were prepared in three different laboratories using the same inks and analyzed using two TDS-GC/MS instruments (one in Munich and one in Wiesbaden). The inter- and intra-laboratory variability of the ageing parameter was determined and ageing curves were compared. While inks stored in similar conditions yielded comparable ageing curves, it was observed that significantly different storage conditions had an influence on the resulting ageing curves. Finally, interpretation models, such as thresholds and trend tests, were evaluated and discussed in view of the obtained results. Trend tests were considered more suitable than threshold models. As both approaches showed limitations, an alternative model, based on the slopes of the ageing curves, was also proposed.

Limited agreement between body mass index, waist and body fat in diagnosing obesity in the Swiss population

Objective: to assess the agreement between different anthropometric markers in defining obesity and the effect on the prevalence of obese subjects. Methods: population-based cross-sectional study including 3213 women and 2912 men aged 35-75 years. Body fat percentage (%BF) was assessed using electric bioimpedance. Obesity was defined using established cut-points for body mass index (BMI) and waist, and three population-defined cut-points for %BF. Between-criteria agreement was assessed by the kappa statistic. Results: in men, agreement between the %BF cut-points was significantly higher (kappa values in the range 0.78 - 0.86) than with BMI or waist (0.47 - 0.62), whereas no such differences were found in women (0.41 - 0.69). In both genders, prevalence of obesity varied considerably according to the criteria used: 17% and 24% according to BMI and waist in men, and 14% and 31%, respectively, in women. For %BF, the prevalence varied between 14% and 17% in men and between 19% and 36% in women according to the cut-point used. In the older age groups, a fourfold difference in the prevalence of obesity was found when different criteria were used. Among subjects with at least one criteria for obesity (increased BMI, waist or %BF), only one third fulfilled all three criteria and one quarter two criteria. Less than half of women and 64% of men were jointly classified as obese by the three population-defined cut-points for %BF. Conclusions: the different anthropometric criteria to define obesity show a relatively poor agreement between them, leading to considerable differences in the prevalence of obesity in the general population.

Sedentarism affects body fat mass index and fat-free mass index in adults aged 18 to 98 years.

OBJECTIVE: Body mass index does not discriminate body fat from fat-free mass or determine changes in these parameters with physical activity and aging. Body fat mass index (BFMI) and fat-free mass index (FFMI) permit comparisons of subjects with different heights. This study evaluated differences in body mass index, BFMI, and FFMI in physically active and sedentary subjects younger and older than 60 y and determined the association between physical activity, age, and body composition parameters in a healthy white population between ages 18 and 98 y. METHODS: Body fat and fat-free mass were determined in healthy white men (n = 3549) and women (n = 3184), between ages 18 and 98 y, by bioelectrical impedance analysis. BFMI and FFMI (kg/m2) were calculated. Physical activity was defined as at least 3 h/wk of endurance-type activity for at least 2 mo. RESULTS: Physically active as opposed to sedentary subjects were more likely to have a low BFMI (men: odds ratio [OR], 1.4; confidence interval [CI], 0.7-2.5; women: OR 1.9, CI 1.6-2.2) and less likely to have very high BFMI (men: OR, 0.2; CI, 0.1-0.2; women: OR, 0.1; CI, 0.02-0.2), low FFMI (men: OR, 0.5; CI, 0.3-0.9; women: OR, 0.7; CI, 0.6-0.9), or very high FFMI (men: OR, 0.6; CI, 0.4-0.8; women: OR, 0.7; CI, 0.5-1.0). Compared with subjects younger than 60 y, those older than 60 y were more like to have very high BFMI (men: OR, 6.5; CI, 4.5-9.3; women: OR, 14.0; CI, 9.6-20.5), and women 60 y and older were less likely to have a low BFMI (OR, 0.4; CI, 0.2-0.5). CONCLUSIONS: A clear association was found between low physical activity or age and height-normalized body composition parameters (BFMI and FFMI) derived from bioelectrical impedance analysis. Physically active subjects were more likely to have high or very high or low FFMI. Older subjects had higher body weights and BFMI.

Detection of metabolite induction in fungal co-cultures on solid media by high-throughput differential ultra-high pressure liquid chromatography-time-of-flight mass spectrometry fingerprinting.

Access to new biological sources is a key element of natural product research. A particularly large number of biologically active molecules have been found to originate from microorganisms. Very recently, the use of fungal co-culture to activate the silent genes involved in metabolite biosynthesis was found to be a successful method for the induction of new compounds. However, the detection and identification of the induced metabolites in the confrontation zone where fungi interact remain very challenging. To tackle this issue, a high-throughput UHPLC-TOF-MS-based metabolomic approach has been developed for the screening of fungal co-cultures in solid media at the petri dish level. The metabolites that were overexpressed because of fungal interactions were highlighted by comparing the LC-MS data obtained from the co-cultures and their corresponding mono-cultures. This comparison was achieved by subjecting automatically generated peak lists to statistical treatments. This strategy has been applied to more than 600 co-culture experiments that mainly involved fungal strains from the Fusarium genera, although experiments were also completed with a selection of several other filamentous fungi. This strategy was found to provide satisfactory repeatability and was used to detect the biomarkers of fungal induction in a large panel of filamentous fungi. This study demonstrates that co-culture results in consistent induction of potentially new metabolites.

Analysis of cannabinoids in oral fluid by liquid chromatography-tandem mass spectrometry

A sensitive method was developed for quantifying a wide range of cannabinoids in oral fluid (OF) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These cannabinoids include a dagger(9)-tetrahydrocannabinol (THC), 11-hydroxy-a dagger(9)-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-a dagger(9)-tetrahydrocannabinol (THCCOOH), cannabinol (CBN), cannabidiol (CBD), a dagger(9)-tetrahydrocannabinolic acid A (THC-A), 11-nor-9-carboxy-a dagger(9)-tetrahydrocannabinol glucuronide (THCCOOH-gluc), and a dagger(9)-tetrahydrocannabinol glucuronide (THC-gluc). Samples were collected using a Quantisal (TM) device. The advantages of performing a liquid-liquid extraction (LLE) of KCl-saturated OF using heptane/ethyl acetate versus a solid-phase extraction (SPE) using HLB copolymer columns were determined. Chromatographic separation was achieved in 11.5 min on a Kinetex (TM) column packed with 2.6-mu m core-shell particles. Both positive (THC, 11-OH-THC, CBN, and CBD) and negative (THCCOOH, THC-gluc, THCCOOH-gluc, and THC-A) electrospray ionization modes were employed with multiple reaction monitoring using a high-end AB Sciex API 5000 (TM) triple quadrupole LC-MS/MS system. Unlike SPE, LLE failed to extract THC-gluc and THCCOOH-gluc. However, the LLE method was more sensitive for the detection of THCCOOH than the SPE method, wherein the limit of detection (LOD) and limit of quantification (LOQ) decreased from 100 to 50 pg/ml and from 500 to 80 pg/ml, respectively. The two extraction methods were successfully applied to OF samples collected from volunteers before and after they smoked a homemade cannabis joint. High levels of THC were measured soon after smoking, in addition to significant amounts of THC-A. Other cannabinoids were found in low concentrations. Glucuronide conjugate levels were lower than the method's LOD for most samples. Incubation studies suggest that glucuronides could be enzymatically degraded by glucuronidase prior to OF collection

Traitement de la dépression résistante par l'association citalopram-lithium. Méthodologie d'une étude multicentrique en double aveugle et résultats préliminaires [Treatment of resistant depression with the citalopram-lithium combination. Methodology of a double-blind multicenter study and preliminary results].

Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy-resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double-blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29-D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu

Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.

Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion. The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate (TU) doping.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. METHODS: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. RESULTS: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >/=30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI 25 kg/m(2) was present only in smokers and drinkers. CONCLUSIONS: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Prepregnancy body mass index and resting metabolic rate during pregnancy.

AIM: The resting metabolic rate (RMR) varies among pregnant women. The factors responsible for this variability are unknown. This study aimed to assess the influence of the prepregnancy body mass index (BMI) on the RMR during late pregnancy. METHODS: RMR, height, weight, and total (TEE) and activity (AEE) energy expenditures were measured in 46 healthy women aged 31 ± 5 years (mean ± SD) with low (<19.8), normal (19.8-26.0), and high (>26.0) prepregnancy BMI at 38.2 ± 1.5 weeks of gestation (t(gest)) and 40 ± 7 weeks postpartum (t(post)) (n = 27). RESULTS: The mean t(gest) RMR for the low-, normal-, and high-BMI groups was 1,373, 1,807, and 2,191 kcal/day, respectively (p = 0.001). The overall mean t(gest) RMR was 316 ± 183 kcal/day (21%), higher than the overall mean t(post) value and this difference was correlated with gestational weight gain (r = 0.78, p < 0.001). The scaled metabolic rate by allometry (RMR/kilograms⁰·⁷³) was similar in the low-, normal-, and high-BMI groups, respectively (p = 0.45). Changes in t(gest) TEE closely paralleled changes in t(gest) RMR (r = 0.84, p < 0.001). AEE was similar among the BMI groups. CONCLUSION: The RMR is significantly increased in the third trimester of pregnancy. The absolute gestational RMR is higher in women with high prepregnancy BMI due to increased body weight. The scaled metabolic rate (RMR/kilograms⁰·⁷³) is similar among the BMI groups of pregnant women.

Estimating parameters for generalized mass action models using constraint propagation.

As modern molecular biology moves towards the analysis of biological systems as opposed to their individual components, the need for appropriate mathematical and computational techniques for understanding the dynamics and structure of such systems is becoming more pressing. For example, the modeling of biochemical systems using ordinary differential equations (ODEs) based on high-throughput, time-dense profiles is becoming more common-place, which is necessitating the development of improved techniques to estimate model parameters from such data. Due to the high dimensionality of this estimation problem, straight-forward optimization strategies rarely produce correct parameter values, and hence current methods tend to utilize genetic/evolutionary algorithms to perform non-linear parameter fitting. Here, we describe a completely deterministic approach, which is based on interval analysis. This allows us to examine entire sets of parameters, and thus to exhaust the global search within a finite number of steps. In particular, we show how our method may be applied to a generic class of ODEs used for modeling biochemical systems called Generalized Mass Action Models (GMAs). In addition, we show that for GMAs our method is amenable to the technique in interval arithmetic called constraint propagation, which allows great improvement of its efficiency. To illustrate the applicability of our method we apply it to some networks of biochemical reactions appearing in the literature, showing in particular that, in addition to estimating system parameters in the absence of noise, our method may also be used to recover the topology of these networks.

The Alcohol Use Disorders Identification Test (AUDIT) as a screening tool for excessive drinking in primary care: reliability and validity of a French version.

BACKGROUND: Excessive drinking is a major problem in Western countries. AUDIT (Alcohol Use Disorders Identification Test) is a 10-item questionnaire developed as a transcultural screening tool to detect excessive alcohol consumption and dependence in primary health care settings. OBJECTIVES: The aim of the study is to validate a French version of the Alcohol Use Disorders Identification Test (AUDIT). METHODS: We conducted a validation cross-sectional study in three French-speaking areas (Paris, Geneva and Lausanne). We examined psychometric properties of AUDIT as its internal consistency, and its capacity to correctly diagnose alcohol abuse or dependence as defined by DSM-IV and to detect hazardous drinking (defined as alcohol intake >30 g pure ethanol per day for men and >20 g of pure ethanol per day for women). We calculated sensitivity, specificity, positive and negative predictive values and Receiver Operator Characteristic curves. Finally, we compared the ability of AUDIT to accurately detect "alcohol abuse/dependence" with that of CAGE and MAST. RESULTS: 1207 patients presenting to outpatient clinics (Switzerland, n = 580) or general practitioners' (France, n = 627) successively completed CAGE, MAST and AUDIT self-administered questionnaires, and were independently interviewed by a trained addiction specialist. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT > or =13 for males, sensitivity 70.1%, specificity 95.2%, PPV 85.7%, NPV 94.7% and for females sensitivity 94.7%, specificity 98.2%, PPV 100%, NPV 99.8%); and hazardous drinkers (with AUDIT > or =7, for males sensitivity 83.5%, specificity 79.9%, PPV 55.0%, NPV 82.7% and with AUDIT > or =6 for females, sensitivity 81.2%, specificity 93.7%, PPV 64.0%, NPV 72.0%). AUDIT gives better results than MAST and CAGE for detecting "Alcohol abuse/dependence" as showed on the comparative ROC curves. CONCLUSIONS: The AUDIT questionnaire remains a good screening instrument for French-speaking primary care.