bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence determinants of subtype‐specific actions of KCNQ channel openers
Authors: Wang Alice W. , Yang Runying , Kurata Harley T. 
Published: August 2016

Key points
Retigabine is a KCNQ voltage‐gated potassium channel opener that was recently approved as an add‐on therapeutic for patients with drug‐resistant epilepsy.
Retigabine exhibits very little specificity between most KCNQ channel subtypes, and there is interest in generating more potent and specific KCNQ channel openers.
The present study describes the marked specificity of ICA069673 for KCNQ2 vs. KCNQ3, and exploits this property to investigate determinants of KCNQ subtype specificity.
ICA069673 acts on a binding site in the voltage‐sensing domain that is distinct from the putative retigabine site in the channel pore.
ICA069673 has two separable effects on KCNQ channel activity. We identify two channel residues required for subtype specificity of KCNQ channel openers and show that these are sufficient to generate ICA069673 sensitivity in KCNQ3.
AbstractRetigabine (RTG) is the first approved anti‐epileptic drug that acts via activation of voltage‐gated potassium channels, targeting KCNQ channels that underlie the neuronal M‐current. RTG exhibits little specificity between KCNQ2–5 as a result of conservation of a Trp residue in the pore domain that binds to the drug. The RTG analogue ICA‐069673 (‘ICA73’) exhibits much stronger effects on KCNQ2 channels, including a large hyperpolarizing shift of the voltage‐dependence of activation, an ∼2‐fold enhancement of peak current and pronounced subtype specificity for KCNQ2 over KCNQ3. Based on ICA73 sensitivity of chimeric constructs of the transmembrane segments of KCNQ2 and KCNQ3, this drug appears to interact with the KCNQ2 voltage sensor (S1–S4) rather than the pore region targeted by RTG. KCNQ2 point mutants in the voltage sensor were generated based on KCNQ2/KCNQ3 sequence differences, and screened for ICA73 sensitivity. These experiments reveal that KCNQ2 residues F168 and A181 in the S3 segment are essential determinants of ICA73 subtype specificity. Mutations at either position in KCNQ2 abolish the ICA73‐mediated gating shift, but preserve RTG sensitivity. Interestingly, A181P mutant channels show little ICA73‐mediated gating shift but retain current potentiation by the drug. Mutations (L198F and P211A), which introduce these critical KCNQ2 residues at corresponding positions in KCNQ3, transplant partial ICA73 sensitivity. These findings demonstrate that RTG and ICA73 act via distinct mechanisms, and also reveal specific residues that underlie subtype specificity of KCNQ channel openers.
Cryotherapy Effects, Part 1: Comparison of Skin Temperatures and Patient-Reported Sensations for Different Modes of Administration
Authors: Love Hailey N. , Pritchard Kimberly A. , Hart Joseph M. , Saliba Susan A. 
Published: August 2016

Context:Alterations in skin sensations may be responsible for pain reduction provided by cryotherapy, but the exact physiological mechanism is unknown.Objective:To investigate perceptions of skin sensations associated with different modes of cryotherapy administration and skin temperature at the point of perceived numbness.Design:Repeated measures.Participants:30 healthy subjects (12 Male, 18 Female, Age = 21.1±1.9 years).Interventions:Crushed ice bag, ice massage, and cold water immersion.Main Outcome Measures:Perceptions of sensations during each mode of cryotherapy administration were derived from a Modified McGill Pain Questionnaire. Skin temperature was recorded when numbness was reported for each treatment.Results:Participants experienced sensations that included cold, tight, tingling, stinging, and numb. Ice massage sensations transitioned rapidly from cold to numb, whereas cold water immersion and ice bag treatments produced altered sensations for longer duration. Ice massage decreased skin temperature significantly more than the other two modes of cryotherapy administration.Conclusions:Ice massage may be the best mode of cryotherapy administration for achievement of anaesthesia as rapidly as possible, whereas cold water immersion and ice bag application may be better for attainment of pain reduction associated with noxious stimulation of skin receptors.
Navicular Drop Before and After Fatigue of the Ankle Invertor Muscles
Authors: Gardin Fredrick Anthony , Middlemas David , Williams Jennifer L. , Leigh Steven , Horn Rob R. 
Published: August 2016

Context:Navicular drop is widely believed to be an indicator of elevated susceptibility to pronation-related injuries, which may be increased by fatigue in the muscles that dynamically support the medial longitudinal arch.Objective:The purpose of this study was to evaluate navicular drop before and after fatigue of the ankle invertor muscles among individuals with different foot types.Participants:20 male and 16 female recreationally active, college-age volunteers (20.03 ± 1.48 years of age).Methods:Navicular drop was measured before and after inducing fatigue in the ankle invertor muscles. Participants’ foot types were classified as high-arch, neutral, or low-arch.Results:There was no interaction between foot type and trial, and no main effect for trial. A main effect for foot type was significant (p = .001). Intra-class correlation coefficients for prefatigue and postfatigue measurements indicated good internal consistency.Conclusion:Our fndings failed to provide any evidence to support the existence of a relationship between ankle invertor muscle fatigue and static measurements of change in navicular height from a sitting to standing position.
Effects of Carbohydrate Supplementation during Intense training on Dietary Patterns, Psychological Status, and Performance
Authors: Kreider Richard B. , Hill Dawn , Horton Greg , Downes Michael , Smith Sarah , Anders Beth 
Published: August 2016

The purpose of this study was to determine the effects of carbohydrate supplementation during intense training on dietary patterns, psychological status, and markers of anaerobic and aerobic performance. Seven members of the U.S. National Field Hockey Team were matched to 7 team counterparts (N = 14). One group was blindly administered a carbohydrate drink containing 1 g·kg−1 of carbohydrate four times daily, while the remaining group blindly ingested a flavored placebo during 7 days of intense training. Subjects underwent pre- and posttraining aerobic and anaerobic assessments, recorded daily diet intake, and were administered the Profile of Mood States (POMS) psychological inventory prior to and following each practice. Results revealed that the carbohydrate-supplemented group had a greater (p < .05) total energy intake, carbohydrate intake, and change (pre vs. post) in time to maximal exhaustion following training while reporting less postpractice psychological fatigue. However, no significant differences were observed in remaining psychological, physiological, or performance-related variables.
Effects of Carbohydrate and Chromium Ingestion during Intermittent High-Intensity Exercise to Fatigue
Authors: Davis J. Mark , Welsh Ralph S. , Alderson Nathan A. 
Published: August 2016

Purpose:This study was designed to test the hypothesis that addition of chromium (Cr) to a carbohydrate-electrolyte drink would enhance the reported benefits of carbohydrate on exercise capacity during intermittent high-intensity shuttle running.Methods:Eight physically active men performed 3 exercise trials while ingesting 6% carbohydrate-electrolyte (CHO), CHO plus chromium picolinate (400 μg) (CHO + Cr+3). or placebo (P) using a double-blind, counterbalanced design. Each trial consisted of 5 × 15 min bouts of shuttle running (walk, sprint, and run at 95 and 55% of estimated V̇O2max, separated by 3-min rest). This was followed by a fatigue test (running alternating 20-m lengths at 55 and 95% of estimated V̇O2, until fatigue).Results:During the standardized shuttle running, blood glucose was higher with both CHO and CHO + Cr+3 than P. Plasma free fatty acid was higher in P than both CHO and CHO + Cr+3 at 75 min of exercise and at fatigue. In the fatigue test, subjects ran longer with both CHO and CHO + Cr+3 than P.Conclusions:The data confirm an ergogenic benefit of ingesting CHO during exercise designed to imitate sports like basketball, soccer, and hockey, but do not support the hypothesis that the addition of Cr would enhance this effect.
Comparison of 24-Hour Whole Body versus Patch Tests for Estimating Body Surface Electrolyte Losses
Authors: Palacios Cristina , Wigertz Karin , Weaver Connie M. 
Published: August 2016

Purpose:To compare dermal electrolyte loss between whole body and regional patch methods in women during 24-h.Methods:Dermal loss was collected in 6 healthy women mean age 27 ± 4 years, while consuming 936 mg/d sodium, 1764 mg/d potassium, 696 mg/d calcium, and 152 mg/d magnesium. Twenty-four hour whole body dermal loss was collected using cotton suits by a washdown procedure. Twenty-four hour patch loss was collected from 8 patches placed on the legs, arms, and back.Results:Dermal loss from whole body was 108 ± 110 mg/d sodium, 133 ± 87 mg/d potassium, 103 ± 22 mg/d calcium, and 35 ± 13 mg/d magnesium. Electrolyte content from the 8 patches was similar among sites and ranged from 1.01–1.41 mg/d sodium, 0.35–0.83 mg/d potassium, 1.0– 1.45 mg/d calcium, and 0.43–0.49 mg/d magnesium. Projections from patches to whole body by the ratio of body surface area appear to overestimate actual whole body losses by 3.2X for sodium and calcium, 3.6X for magnesium, and 1.3X for potassium.Conclusions:Regional patch methods are more appropriate for relative comparisons than for accurately determining total daily dermal electrolyte losses.
Endurance Training on Low-Carbohydrate and Grain-Based Diets: A Case Study
Authors: Rosenkranz Richard R. , Cook Chad M. , Haub Mark D. 
Published: August 2016

Purpose:To illustrate the effects of low-carbohydrate (LC) and grain-based (GB) diets on body composition, biomarkers, athletic training, and performance in an elite triathlete.Methods:The athlete followed 2 dietary interventions for 14 d while maintaining a prescheduled training program. Pre- and post intervention measurements for each diet included plasma and serum samples, resting energy expenditure, body composition, and a performance bike ride.Results:Compared with the GB diet, the LC diet elicited more disruptions to training and unfavorable subjective experiences. Total cholesterol, HDL cholesterol, LDL cholesterol, ratings of perceived exertion, and heart rate were elevated on the LC diet. Blood insulin, resting lactate, post exercise lactate, and C-reactive protein were lowest on the LC diet.Conclusion:The LC diet resulted in both favorable and unfavorable outcomes. The primary observation was a disruption to scheduled training on the LC diet. Researchers should consider how the potential mediating effect of disruptions to training could influence pretest–posttest designs.
Changes in Resting Metabolic Rate and Substrate Oxidation after 16 Months of Exercise Training in Overweight Adults
Authors: Potteiger Jeffrey A. , Kirk Erik P. , Jacobsen Dennis J. , Donnelly Joseph E. 
Published: August 2016

Purpose:To determine whether 16 months of moderate-intensity exercise training changes resting metabolic rate (RMR) and substrate oxidation in overweight young adults.Methods:Participants were randomly assigned to nonexercise control (CON, 18 women, 15 men) or exercise (EX, 25 women, 16 men) groups. EX performed supervised and verified exercise 3–5 d/wk, 20–45 min/session, at 60–75% of heart-rate reserve. Body mass and composition, maximal oxygen consumption (VO2max), RMR, and resting substrate oxidation were assessed at baseline and after 9 and 16 months of training.Results:EX men had significant decreases from baseline to 9 months in body mass (94.6 ± 12.4 to 89.2 ± 9.5 kg) and percent fat (28.3 ± 4.6 to 24.5 ± 3.9). CON women had significant increases in body mass (80.2 ± 8.1 to 83.2 ± 9.2 kg) from baseline to 16 months. VO2max increased significantly from baseline to 9 months in the EX men (3.67 ± 0.62 to 4.34 ± 0.58 L/min) and EX women (2.53 ± 0.32 to 3.03 ± 0.42 L/min). RMR increased from baseline to 9 months in EX women (1,583 ± 221 to 1,692 ± 230 kcal/d) and EX men (1,995 ± 184 to 2,025 ± 209 kcal/d). There were no significant differences within genders for either EX or CON in fat or carbohydrate oxidation. Fat oxidation was significantly higher for women than for men at 9 months in both CON and EX groups.Conclusions:Regular moderate-intensity exercise in healthy, previously sedentary overweight and obese adults increases RMR but does not alter resting substrate oxidation. Women tend to have higher RMR and greater fat oxidation, when expressed per kilogram fat-free mass, than men.
Dose Effect of Caffeine on Testosterone and Cortisol Responses to Resistance Exercise
Authors: Beaven C. Martyn , Hopkins Will G. , Hansen Kier T. , Wood Matthew R. , Cronin John B. , Lowe Timothy E. 
Published: August 2016

Introduction:Interest in the use of caffeine as an ergogenic aid has increased since the International Olympic Committee lifted the partial ban on its use. Caffeine has beneficial effects on various aspects of athletic performance, but its effects on training have been neglected.Purpose:To investigate the acute effect of caffeine on the exercise-associated increases in testosterone and cortisol in a double-blind crossover study.Methods:Twenty-four professional rugby-league players ingested caffeine doses of 0, 200, 400, and 800 mg in random order 1 hr before a resistance-exercise session. Saliva was sampled at the time of caffeine ingestion, at 15-min intervals throughout each session, and 15 and 30 min after the session. Data were log-transformed to estimate percent effects with mixed modeling, and effects were standardized to assess magnitudes.Results:Testosterone concentration showed a small increase of 15% (90% confidence limits, ± 19%) during exercise. Caffeine raised this concentration in a dose-dependent manner by a further small 21% (± 24%) at the highest dose. The 800-mg dose also produced a moderate 52% (± 44%) increase in cortisol. The effect of caffeine on the testosterone:cortisol ratio was a small decline (14%; ± 21%).Conclusion:Caffeine has some potential to benefit training outcomes via the anabolic effects of the increase in testosterone concentration, but this benefit might be counteracted by the opposing catabolic effects of the increase in cortisol and resultant decline in the testosterone:cortisol ratio.
Influence of Carbohydrate-Protein Beverage on Cycling Endurance and Indices of Muscle Disruption
Authors: Valentine Rudy J. , Saunders Michael J. , Todd M. Kent , St. Laurent Thomas G. 
Published: August 2016

Carbohydrate–protein (CHO+Pro) beverages reportedly improve endurance and indices of muscle disruption, but it is unclear whether these effects are related to total energy intake or specific effects of protein.Purpose:The authors examined effects of CHO+Pro on time to exhaustion and markers of muscle disruption compared with placebo (PLA) and carbohydrate beverages matched for carbohydrate (CHO) and total calories (CHO+CHO).Methods:Eleven male cyclists completed 4 rides to exhaustion at 75% VO2peak. Participants consumed 250 ml of PLA, CHO (7.75%), CHO+CHO (9.69%), or CHO+Pro (7.75%/1.94%) every 15 min until fatigue, in a double-blind design.Results:Time to exhaustion was significantly longer (p < .05) in CHO+Pro (126.2 ± 25.4 min) and CHO+CHO (121.3 ± 36.8) than PLA (107.1 ± 30.3). CHO (117.5 ± 24.2) and PLA were not significantly different. Similarly, CHO+Pro was not significantly different from CHO and CHO+CHO. Postexercise plasma creatine kinase was lower after CHO+Pro (197.2 ± 149.2 IU/L) than PLA (407.4 ± 391.3), CHO (373.2 ± 416.6), and CHO+CHO (412.3 ± 410.2). Postexercise serum myoglobin was lower in CHO+Pro (47.0 ± 27.4 ng/mL) than all other treatments (168.8 ± 217.3, 82.6 ± 71.3, and 72.0 ± 75.8). Postexercise leg extensions at 70% 1RM were significantly greater 24 hr after CHO+Pro (11.3 ± 4.1) than PLA (8.8 ± 3.7), CHO (9.7 ± 4.3), and CHO+CHO (9.5 ± 3.6).Conclusion:These findings suggest that at least some of the reported improvements in endurance with CHO+Pro beverages might be related to caloric differences between treatments. Postexercise improvements in markers of muscle disruption with CHO+Pro ingestion appear to be independent of carbohydrate and caloric content and were elicited with beverages consumed only during exercise.
Nutritional Habits of Flemish Adolescent Sprint Athletes
Authors: Aerenhouts Dirk , Hebbelinck Marcel , Poortmans Jacques R. , Clarys Peter 
Published: August 2016

Purpose and Methods:To investigate dietary habits of Flemish adolescent track and field athletes using a 7-d weighed-food record. Besides adequacy for growth, development, and physical performance, dietary health aspects were considered.Results:Twenty-nine girls and 31 boys, with minimum 2 yr of track and field training practice, were recruited. All participants had daily breakfast (girls 22.5% ± 5.5% of total energy intake [TEI]; boys 19.8% ± 7.3%). Fruit in girls and juices and sports drinks in boys were consumed mostly between meals (girls 21.3% ± 8.1% of TEI; boys 24.3% ± 10.1%). Soft drinks contributed considerably to energy intake between meals in both sexes. Protein intake (1.5 ± 0.3 g · kg–1 · d−1 for both sexes) was within the recommended daily intake (RDI) for strength athletes. Mean daily carbohydrate intake in girls was lower than in boys (girls 5.1 ± 1.1 g/kg; boys 6.0 ± 0.9 g/kg), with mono- and disaccharides contributing 26% to TEI in both sexes. Total fat intake was above 30% of TEI in more than half the participants, and only 10 participants had a saturated-fat intake below 10% of TEI. Fiber intake (girls 23.7 ± 7.9 g; boys 29.1 ± 11.2 g) was far below the Belgian RDI. Intake of vitamins and minerals were generally low, despite micronutrient supplementation in 37.5% of the participants.Conclusion:Few athletes reached all nutrient RDIs. Unhealthy food habits with regard to refined sugars, fat, and micronutrients were observed. These adolescent sprinters should be encouraged to consume more nonsweetened beverages, fruits, and vegetables.
Plasma Amino Acid Responses after Consumption of Beverages with Varying Protein Type
Authors: Smith Tracey J. , Montain Scott J. , Anderson Danielle , Young Andrew J. 
Published: August 2016

Purpose:To examine how different proteins in a carbohydrate-protein beverage affect postprandial amino acid (AA), glucose, and insulin responses.Methods:Two randomized, repeated-measures experiments were performed. In one, 10 volunteers drank 3 carbohydrate-protein beverages (380 kcal, 76 g carbohydrate, 19 g protein, 2 g fat) in separate (>7 days) trials, each differing in protein type. All drinks consisted of cocoa (4 g) and nonfat dry milk (1 g) supplemented with casein (CAS), whey (WP), or a casein and whey blend (CAS-WP). Ten additional volunteers consumed the same drinks after 60 min of varying-intensity exercise (60% and 85% VO2peak). Blood glucose, insulin, glucose-dependent insulinotrophic polypeptide (GIP), and AAs were measured every 15–30 min for 4 hr after beverage consumption.Results:Branchedchain AA concentrations peaked at 30 min and did not differ between beverages at rest (0.69 ± 0.12 mmol/L) or postexercise (0.70 ± 0.07 mmol/L). There were no significant differences between beverages with respect to initial (time 0–60) or total area under the curve (time 0–240) for any outcome measures at rest or postexercise.Conclusion:High-carbohydrate beverages containing various proportions of milk proteins procured from a supplier to the commercial industry had no impact on AA concentration. Retrospective chemical analysis of commercial proteins showed that casein was partially hydrolyzed; therefore, consumers should carefully consider the manufacturer (to ensure that the product contains intact protein) or other factors (i.e., cost or taste) when procuring these beverages for their purported physiological effects.
Changes in Body Composition with Yogurt Consumption during Resistance Training in Women
Authors: White Kimberly M. , Bauer Stephanie J. , Hartz Kristopher K. , Baldridge Monika 
Published: August 2016

Introduction:Resistance training is an effective method to decrease body fat (BF) and increase fat-free mass (FFM) and fat oxidation (FO). Dairy foods containing calcium and vitamin D might enhance these benefits. This study investigated the combined effects of habitual yogurt consumption and resistance training on body composition and metabolism.Methods:Untrained women (N = 35) participated in an 8-wk resistance-training program. The yogurt group (Y) consumed 3 servings of yogurt containing vitamin D per day, and the control groups maintained their baseline lowdairy-calcium diet. Postexercise, Y consumed 1 of the 3 servings/d fat-free yogurt, the protein group consumed an isocaloric product without calcium or vitamin D, and the carbohydrate group consumed an isocaloric product without protein. Strength, body composition, fasted resting metabolic rate (RMR) and FO, and serum 25-hydroxyvitamin D were measured before and after training.Results:Calories (kcal · kg−1 · d−1) and protein (g · kg−1 · d−1) significantly increased from baseline for Y. FFM increased (main effect p = .002) and %BF decreased (main effect .02) for all groups with training, but Group × Time interactions were not observed. RMR and FO did not change with training for any group.Conclusion:Habitual consumption of yogurt during resistance training did not augment changes in body composition compared with a low-dairy diet. Y decreased %BF as a result of training, however, even with increased calorie consumption.
Duathlon Performance Unaltered by Short-Term Changes in Dietary Fat and Carbohydrates
Authors: Moncada-Jiménez José , Plaisance Eric P. , Mestek Michael L. , Ratcliff Lance , Araya-Ramírez Felipe , Taylor James K. , Grandjean Peter W. , AragónVargas Luis F. 
Published: August 2016

Purpose:This study investigated the effects of short-term dietary changes on metabolism and duathlon performance.Methods:Eleven men underwent a high-fat (HF; >65% fat from energy) or a high-carbohydrate (CHO; HC) diet (>60% CHO from energy). Energy intake was individualized, and commercially available foods were prepared and packaged for each participant 48 hr before they completed a laboratory-based duathlon (5-km run, 30 km cycling, and 10-km run). Blood samples were obtained before, immediately after, and 1 and 2 hr after the duathlon for determination of glucose, insulin, and glucagon. Oxygen consumption, ratings of perceived exertion (RPE), and respiratory-exchange ratio were assessed, and fat and CHO oxidation were estimated before, during, and after the duathlon.Results:Dietary records indicated a significant difference in fat content ingested before the duathlons (p < .05). Time to complete the duathlon did not differ between the HC- and the HF-diet trials. CHO-oxidation rate was higher during the HC-diet trial than during the HF-diet trial (p = .006). Fat-oxidation rates were higher in the HF-diet trial than in the HC-diet trial (p = .001). No differences in RPE were found between dietary trials. Blood glucose concentration was higher immediately after the duathlon in the HC-diet trial than in the HF-diet trial and remained higher 1 and 2 hr after the duathlon (p < .05).Conclusion:Duathlon performance was not altered by short-term changes in dietary fat or CHO composition despite higher blood glucose concentrations under the HC condition.