Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

How does a hilly urban environment influence daily physical activity in obese individuals?

Background: Increases in physical activity (PA) are promoted by walking in an outdoor environment. Along with walking speed, slope is a major determinant of exercise intensity, and energy expenditure. The hypothesis was that in free-living conditions, a hilly environment diminishes PA to a greater extent in obese (OB) when compared with control (CO) individuals. Methods: To assess PA types and patterns, 28 CO (22 ± 2 kg/m2) and 14 OB (33 ± 4 kg/m2) individuals wore during an entire day 2 accelerometers and 1 GPS device, around respectively their waist, ankle and shoulder. They performed their usual PA and were asked to walk an additional 60 min per day. Results: The duration of inactivity and activity with OB individuals tended to be, respectively, higher and lower than that of CO individuals (P = .06). Both groups spent less time walking uphill/downhill than on the level (20%, 19%, vs. 61% of total walking duration, respectively, P < .001). However OB individuals spent less time walking uphill/downhill per day than CO (25 ± 15 and 38 ± 15 min/d, respectively, P < 0.05) and covered a shorter distance per day (3.8 km vs 5.2 km, P < 0.01). Conclusions: BMI and outdoor topography should also be considered when prescribing extra walking in free-living conditions.

Influence of hip-flexion angle on hamstrings isokinetic activity in sprinters.

CONTEXT: Hamstrings strains are common and debilitating injuries in many sports. Most hamstrings exercises are performed at an inadequately low hip-flexion angle because this angle surpasses 70° at the end of the sprinting leg's swing phase, when most injuries occur. OBJECTIVE: To evaluate the influence of various hip-flexion angles on peak torques of knee flexors in isometric, concentric, and eccentric contractions and on the hamstrings-to-quadriceps ratio. DESIGN: Descriptive laboratory study. SETTING: Research laboratory. Patients and Other Participants: Ten national-level sprinters (5 men, 5 women; age = 21.2 ± 3.6 years, height = 175 ± 6 cm, mass = 63.8 ± 9.9 kg). Intervention(s): For each hip position (0°, 30°, 60°, and 90° of flexion), participants used the right leg to perform (1) 5 seconds of maximal isometric hamstrings contraction at 45° of knee flexion, (2) 5 maximal concentric knee flexion-extensions at 60° per second, (3) 5 maximal eccentric knee flexion-extensions at 60° per second, and (4) 5 maximal eccentric knee flexionextensions at 150° per second. Main Outcome Measure(s): Hamstrings and quadriceps peak torque, hamstrings-to-quadriceps ratio, lateral and medial hamstrings root mean square. RESULTS: We found no difference in quadriceps peak torque for any condition across all hip-flexion angles, whereas hamstrings peak torque was lower at 0° of hip flexion than at any other angle (P < .001) and greater at 90° of hip flexion than at 30° and 60° (P < .05), especially in eccentric conditions. As hip flexion increased, the hamstrings-to-quadriceps ratio increased. No difference in lateral or medial hamstrings root mean square was found for any condition across all hip-flexion angles (P > .05). CONCLUSIONS: Hip-flexion angle influenced hamstrings peak torque in all muscular contraction types; as hip flexion increased, hamstrings peak torque increased. Researchers should investigate further whether an eccentric resistance training program at sprint-specific hip-flexion angles (70° to 80°) could help prevent hamstrings injuries in sprinters. Moreover, hamstrings-to-quadriceps ratio assessment should be standardized at 80° of hip flexion.

Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance.

Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.

The influence of bacterial activity on phosphorite formation in the Miocene Monterey Formation, California

Authigenic phosphorites from the Miocene Monterey Formation (California) including an autochthonous phosphatic laminite were analyzed for molecular biomarkers, element content, and sulfur isotopic composition of associated pyrite and sulfate to evaluate the role of bacterial activity in the precipitation of phosphate minerals. The phosphorites formed in a depositional environment typified by upwelling with dynamic bottom currents and hardground formation. Pyrite enclosed in the phosphorites shows delta S-34 values as low as -36.5 parts per thousand VCDT, which is consistent with bacterial sulfate reduction. In a three-step extraction phosphorite dissolution extraction procedure, molecular fossils of sulfate-reducing bacteria (di-O-alkyl glycerol ethers and short-chain branched fatty acids i- and ai-C-15:0, i- and ai-C-17:0, and 10MeC(16:0)) were preferentially released from the mineral lattice. This suggests that the molecular fossils were tightly bound to carbonate fluorapatite, indicating that sulfate-reducing bacteria were involved in mineral formation. A close association of sulfate-reducing bacteria with large sulfide-oxidizing bacteria, which was previously suggested to favor carbonate fluorapatite precipitation, could neither be confirmed nor excluded for the Miocene Monterey Formation phosphorites. (C) 2012 Elsevier B.V. All rights reserved.

Carbonic anhydrase activity in primary sensory neurons. II. Influence of environmental factors on the phenotypic expression of the enzyme in dissociated cultures of chicken dorsal root ganglion cells.

Neuronal subpopulations of dorsal root ganglion (DRG) cells in the chicken exhibit carbonic anhydrase (CA) activity. To determine whether CA activity is expressed by DRG cells maintained in in vitro cultures, dissociated DRG cells from 10-day-old chick embryos were cultured on a collagen substrate. The influence exerted by environmental factors on the enzyme expression was tested under various conditions of culture. Neuron-enriched cell cultures and mixed DRG-cell cultures (including numerous non-neuronal cells) were performed either in a defined medium or in a horse serum-supplemented medium. In all the tested conditions, subpopulations of cultured sensory neurons expressed CA activity in their cell bodies, while their neurites were rarely stained; in each case, the percentage of CA-positive neurons declined with the age of the cultures. The number and the persistence of neurons possessing CA activity as well as the intensity of the reaction were enhanced by addition of horse serum. In contrast, the expression of the neuronal CA activity was not affected by the presence of non-neuronal cells or by the rise of CO2 concentration. Thus, the appearance and disappearance of neuronal subpopulations expressing CA activity may be decisively influenced by factors contained in the horse serum. The loss of CA-positive neurons with time could result from a cell selection or from genetic repression. Analysis of the time curves does not support a preferential cell death of CA-positive neurons but suggests that the eventual conversion of CA-positive neurons into CA-negative neurons results from a loss of the enzyme activity. These results indicate that the phenotypic expression of cultured sensory neurons is dependent on defined environmental factors.

'A pilot study to investigate external urethral sphincter electromyographic activity and the influence of hormonal changes in the menstrual cycle'

But de l'étude Un enregistrement spécifique EMG du sphincter strié urétral avec décharges répétitives et complexes ainsi que salves de décélération a été décrit comme pathognomonique du syndrome de Fowler, un trouble de la relaxation du sphincter strié urétral chez la femme jeune responsable d'une retention urinaire. Nous avons souhaité étudier la présence de cet enregistrement EMG spécifique chez la femme asymptomatique, ceci à différents moments du cycle menstruel. Matériel et Méthode Nous avons recruté des femmes volontaires saines âgées entre 20 et 40 ans, ayant un cycle hormonal régulier, et ne présentant aucun symptôme urinaire. Les critères d'exclusion étaient la presence d'une dysfonction mictionnelle, d'une infection urinaire, la grossesse, la prise d'une thérapie hormonale ou d'hormone contraceptive, une obésité et des antécédants d'intervention pelvienne. Nous avons procédé à deux enregistrements EMG du sphincter strié urétral des participantes éligibles, utilisant une aiguille concentrique, ceci dans la première phase du cycle (phase folliculaire) et dans la dernière phase du cycle (phase lutéale). Les taux sériques de progestérone et d'oestrogène étaient mesurés à chaque enregistrement. Résultats 15 participantes ont complété l'étude. L' enregistrement EMG du sphincter a été positif avec présence de décharges répétitives et de salves de décélération lors d'une ou des deux phases du cycle menstruel chez 8 participantes (53%). Trois participantes présentaient cet enregistrement spécifique lors des deux phases du cycle et cinq participantes présentaient cet enregistrement spécifique lors de la phase lutéale uniquement. Aucune femme ne présentait cet enregistrement spécifique en début de cycle uniquement. Il n'y avait pas de relation avec l'âge, la parité ou les taux hormonaux. Conclusions L'enregistrement EMG spécifique du sphincter strié urétral, avec décharges répétitives et salves de décélération, se retrouve chez une proportion élevée de femmes asymptomatiques. Il a été montré que ce tracé change lors du cycle menstruel, en étant retrouvé plus fréquemment dans la dernière phase du cycle. L'importance de cet enregistrement EMG dans l'étiologie de la retention urinaire de la femme jeune reste à éclaircir. Nous devons considérer que sa présence ne pose pas automatiquement un diagnostic de syndrome de Fowler chez la femme en rétention urinaire.

Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.

Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.

Impairment and disability in 20 CIDP patients according to disease activity status.

Twenty patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) meeting the EFNS/PNS criteria were examined in order to assess differences/similarities between the various grading systems according to CIDP disease activity status (CDAS). A principal component (PC) analysis and the correlations between the following scores were performed: Neurological Symptom Score; MRC sum score; Neurological Impairment Score; Hammersmith Functional Motor Scale; Inflammatory Neuropathy Cause and Treatment (INCAT) Sensory Sum Score; Overall Disability Sum Score; INCAT Disability Score; Rasch-built Overall Disability Scale. Our analysis outlined two main sets of scales, with high influence in the top two PCs. The first PC that best explained the variability within the cohort consisted of CDAS, general disability scores and motor scores; these parameters were also strongly correlated amongst each other. The second PC explained less the variability and consisted mainly of sensory scores and disease duration; these parameters did not correlate with the scores of the first PC or with the CDAS. Our findings suggest separating screening for motor and sensory deficits when evaluating CIDP patients, as only the motor scores correlate with CDAS.

How multiple repetitions influence the processing of self-, famous and unknown names and faces: an ERP study.

Because we live in an extremely complex social environment, people require the ability to memorize hundreds or thousands of social stimuli. The aim of this study was to investigate the effect of multiple repetitions on the processing of names and faces varying in terms of pre-experimental familiarity. We measured both behavioral and electrophysiological responses to self-, famous and unknown names and faces in three phases of the experiment (in every phase, each type of stimuli was repeated a pre-determined number of times). We found that the negative brain potential in posterior scalp sites observed approximately 170 ms after the stimulus onset (N170) was insensitive to pre-experimental familiarity but showed slight enhancement with each repetition. The negative wave in the inferior-temporal regions observed at approximately 250 ms (N250) was affected by both pre-experimental (famous>unknown) and intra-experimental familiarity (the more repetitions, the larger N250). In addition, N170 and N250 for names were larger in the left inferior-temporal region, whereas right-hemispheric or bilateral patterns of activity for faces were observed. The subsequent presentations of famous and unknown names and faces were also associated with higher amplitudes of the positive waveform in the central-parietal sites analyzed in the 320-900 ms time-window (P300). In contrast, P300 remained unchanged after the subsequent presentations of self-name and self-face. Moreover, the P300 for unknown faces grew more quickly than for unknown names. The latter suggests that the process of learning faces is more effective than learning names, possibly because faces carry more semantic information.

Influence of inflammation on total energy expenditure in hemodialysis patients.

Background and Objectives: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients.Design: This was a cross-sectional study.Setting: This study was conducted from Hopital Edouard Herriot, Lyon, France.Patients: This study included 24 HD patients and 18 healthy subjects.Main Outcome Measure: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein,5 mg/L, aged 67.0 +/- 6 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 +/- 6 18.0 years) and compared with 18 healthy subjects (62.3 +/- 6 15.3 years).Results: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 +/- 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 +/- 6.7 kcal/kg/day) and with healthy subjects (31.8 +/- 6 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 +/- 5,419 and 6,016 +/- 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 +/- 2,754 steps/day, P = .001).Conclusion: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.