Effects of reduced-volume of sprint interval training and the time course of physiological and performance adaptations

This study sought to determine the time course of training adaptations to two different sprint interval training programmes with the same sprint: rest ratio (1:8) but different sprint duration. Nine participants (M: 7; F: 2) were assigned to 15-s training group (15TG) consisting of 4 to 6 x 15-s sprints interspersed with 2-min recovery, whereas eight participants (M: 5; F: 3) were assigned to 30-s training group (30TG) consisting of 4 to 6 30-s sprints interspersed with 4-min recovery. Both groups performed their respective training twice per week over 9 weeks and changes in peak oxygen uptake (V̇O2peak) and time to exhaustion (TTE) were assessed every 3 weeks. Additional 8 healthy active adults (M: 6; F: 2) completed the performance assessments 9 weeks apart without performing training (control group, CON). Following 9 weeks of training, both groups improved V̇O2peak (15TG: 12.1%; 30TG: 12.8%, P < 0.05) and TTE (15TG: 16.2%; 30TG: 12.8%, P < 0.01) to a similar extent. However, while both groups showed the greatest gains in V̇O2peak at 3 weeks (15TG: 16.6%; 30TG: 17.0%, P < 0.001), those in TTE were greatest at 9 weeks. CON did not change any of performance variables following 9 weeks. This study demonstrated that whilst the changes in cardiorespiratory function plateau within several weeks with sprint interval training, endurance capacity (TTE) is more sensitive to such training over a longer time frame in moderately-trained individuals. Furthermore, a 50% reduction in sprint duration does not diminish overall training adaptations over 9 weeks

International Society of Sports Nutrition position stand: beta-alanine

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4–6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine

Re-Examination of Possible Bimodality of GALLEX Solar Neutrino Data

The histogram formed from published capture-rate measurements for the GALLEX solar neutrino experiment is bimodal, showing two distinct peaks. On the other hand, the histogram formed from published measurements derived from the similar GNO experiment is unimodal, showing only one peak. However, the two experiments differ in run durations: GALLEX runs are either three weeks or four weeks (approximately) in duration, whereas GNO runs are all about four weeks in duration. When we form 3-week and 4-week subsets of the GALLEX data, we find that the relevant histograms are unimodal. The upper peak arises mainly from the 3-week runs, and the lower peak from the 4-week runs. The 4-week subset of the GALLEX dataset is found to be similar to the GNO dataset. A recent re-analysis of GALLEX data leads to a unimodal histogram.Comment: 14 pages, 8 figure

Phase 1b/2a trial of the superoxide dismutase mimetic GC4419 to reduce chemoradiotherapy-induced oral mucositis in patients with oral cavity or oropharyngeal carcinoma

PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending \u3c60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT. RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days. CONCLUSIONS: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected

Prospective evaluation of a protocol for transitioning porcine lente insulintreated diabetic cats to human recombinant protamine zinc insulin

Objectives The objective was to evaluate a nadir-led protocol for transitioning porcine lente insulin suspension (PLIS)-treated diabetic cats onto human recombinant protamine zinc insulin (PZIR). Methods Recently diagnosed (<5 months) diabetic cats, treated with PLIS q12h for 6 weeks, were recruited. Fructosamine, 24 h blood glucose curve (BGC), quality of life assessment (DIAQoL-pet score) and Diabetic Clinical Score (DCS) were assessed at enrolment (PLIS-treated) and 2, 4 and 12 weeks after transitioning to PZIR (starting dose 0.2-0.7 U/kg q12h). Short duration of insulin action was defined as <9 h. Linear mixed effects modelling assessed for change in fructosamine, mean blood glucose (MBG) during BGCs, DIAQoL-pet score, DCS and q12h insulin dose. McNemar's tests compared the proportion of cats with hypoglycaemia at week 0 (PLIS-treated) and week 4 (PZIR-treated). Results Twenty-two cats were recruited. Median PLIS dose at enrolment was 0.5 U/kg (interquartile range 0.3-0.7 U/kg) q12h, equalling median PZIR starting dose (0.5 U/kg; interquartile range 0.3-0.7 U/kg q12h). Transitioning was followed by significant decreases in fructosamine (P = 0.00007), insulin dose (P = 0.02), DCS (P = 8.1 x 10(-8)) and DIAQoL-pet score (P = 0.003), indicating improved quality of life. MBG did not alter significantly (P = 0.1). Five cats (22.7%) achieved remission. Hypoglycaemia was recorded in 30/190 12 h BGCs (15.8%) and five cats experienced clinical hypoglycaemia. The proportion of cats with hypoglycaemia did not differ between PLIS (week 0) and PZIR (week 4) (P = 1.0). Duration of action was analysed in 19 cats. Six cats (31.6%) showed short duration of action on PLIS, compared with two cats (10.5%) after 4 weeks on PZIR. All six cats with short PLIS duration showed duration of 9 h on PZIR. Conclusions and relevance Used alongside a low-carbohydrate diet, transitioning to PZIR was associated with significantly improved clinical signs and quality of life, with some cats achieving remission. Transition to PZIR should be considered for cats with short duration of action on PLIS

Fremanezumab for the Preventive Treatment of Chronic Migraine.

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .)

Responses of heat shock protein 70 and caspase-3/7 to dietary selenomethionine in juvenile white sturgeon.

An 8-week feeding trial was conducted to investigate the responses of juvenile white sturgeon (Acipenser transmontanus) to elevated dietary selenium (Se) based on the determination of the RNA/DNA ratio in muscle, heat shock protein 70 (Hsp70), and caspase-3/7 in muscle and/or liver tissues. Four semi-purified test diets were prepared by adding different levels of L-selenomethionine (0, 50, 100, and 200 mg/kg diet). The analytical determinations of total Se were 2.2, 19.7, 40.1, and 77.7 mg/kg diet. The sturgeon (initial body weight: 30 ± 2 g; mean ± SEM) were raised in indoor tanks provided with flow through freshwater (18-19 °C). There were three replicates for each dietary treatment with 25 fish per replicate. The liver and muscle tissues were collected at 4 and 8 weeks after feeding the test diets. A significant interaction between duration and levels of dietary Se exposures on RNA/DNA ratio in the muscle tissue was detected (P &lt; 0.05). Although there was no significant main effect due to the duration of dietary Se exposures (i.e., 4 weeks versus 8 weeks) on muscle RNA/DNA ratio (P ≥ 0.05), the ratio was significantly decreased with increasing dietary Se levels. Significant main effects were caused by the duration and levels of dietary Se exposures on Hsp70 in both the muscle and liver tissues, with significant increases in Hsp70 due to a longer exposure (8 weeks) and higher levels (40.1 and 77.7 mg Se/kg diet) of dietary Se. The caspase-3/7 activity in the liver were significantly higher in fish fed the diets containing 40.1 and 77.7 mg Se/kg diet than those fed the other diets. The toxic thresholds of Se in the muscle were estimated to be 32.2 and 26.6 mg Se/kg for the depressed specific growth rate and the induced Hsp70 response in muscle, respectively. This result indicated that the Hsp70 response in muscle is a more sensitive biomarker than the SGR of sturgeon for evaluating Se toxicity in white sturgeon. Results of the current study suggest that a mechanism involved with the activation of stress protein production and apoptosis protects white sturgeon from the lethal effect of Se

Hollywood blockbusters and long-tailed distributions: An empirical study of the popularity of movies

Numerical data for all movies released in theaters in the USA during the period 1997-2003 are examined for the distribution of their popularity in terms of (i) the number of weeks they spent in the Top 60 according to the weekend earnings, and (ii) the box-office gross during the opening week, as well as, the total duration for which they were shown in theaters. These distributions show long tails where the most popular movies are located. Like the study of Redner [S. Redner, Eur. Phys. J. B 4, 131 (1998)] on the distribution of citations to individual papers, our results are consistent with a power-law dependence of the rank distribution of gross revenues for the most popular movies with a exponent close to -1/2.Comment: 4 pages, 4 figure

Increase in neuroexcitability of unmyelinated C-type vagal ganglion neurons during initial postnatal development of visceral afferent reflex functions

BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function

Investigating A Dose Response Relationship between High Fat Diet Consumption and the Contractile Performance of Isolated Mouse Soleus, EDL and Diaphragm Muscles

PurposeRecent evidence has demonstrated an obesity-induced, skeletal muscle-specific reduction in contractile performance. The extent and magnitude of these changes in relation to total dose of high-fat diet consumption remains unclear. This study aimed to examine the dose–response relationship between a high-fat diet and isolated skeletal muscle contractility.Methods120 female CD1 mice were randomly assigned to either control group or groups receiving 2, 4, 8 or 12 weeks of a high-calorie diet (N = 24). At 20 weeks, soleus, EDL or diaphragm muscle was isolated (n = 8 in each case) and isometric force, work loop power output and fatigue resistance were measured.ResultsWhen analysed with respect to feeding duration, there was no effect of diet on the measured parameters prior to 8 weeks of feeding. Compared to controls, 8-week feeding caused a reduction in normalised power of the soleus, and 8- and 12-week feeding caused reduced normalised isometric force, power and fatigue resistance of the EDL. Diaphragm from the 12-week group produced lower normalised power, whereas 8- and 12-week groups produced significantly lower normalised isometric force. Correlation statistics indicated that body fat accumulation and decline in contractility will be specific to the individual and independent of the feeding duration.ConclusionThe data indicate that a high-fat diet causes a decline in muscle quality with specific contractile parameters being affected in each muscle. We also uniquely demonstrate that the amount of fat gain, irrespective of feeding duration, may be the main factor in reducing contractile performance