Continuous Research Articles

Continuous Versus Intermittent Running: Acute Performance Decrement and Training Load.

To examine the effect of continuous (CON) and intermittent (INT) running training sessions of different durations and intensities on subsequent performance and calculated training load (TL). Runners (N = 11) performed a 1500-m time trial as a baseline and after completing 4 different running training sessions. The training sessions were performed in a randomized order and were either maximal for 10minutes (10CON and 10INT) or submaximal for 25minutes (25CON and 25INT). An acute performance decrement (APD) was calculated as the percentage change in 1500-m time-trial speed measured after training compared with baseline. The pattern of APD response was compared with that for several TL metrics (bTRIMP, eTRIMP, iTRIMP, running training stress score, and session rating of perceived exertion) for the respective training sessions. Average speed (P < .001, ηp2=.924) was different for each of the initial training sessions, which all resulted in a significant APD. This APD was similar when compared across the sessions except for a greater APD found after 10INT versus 25CON (P = .02). In contrast, most TL metrics were different and showed the opposite response to APD, being higher for CON versus INT and lower for 10- versus 25-minute sessions (P < .001, ηp2>.563). An APD was observed consistently after running training sessions, but it was not consistent with most of the calculated TL metrics. The lack of agreement found between APD and TL suggests that current methods for quantifying TL are flawed when used to compare CON and INT running training sessions of different durations and intensities.

An assessment of dose-dependent UV-B sensitivity in Eclipta alba: Biochemical traits, antioxidative properties, and wedelolactone yield.

The UV-B-induced signals play a crucial role in improving the analeptic values of medicinally important plants. Eclipta alba L. (Hassak), commonly known as False Daisy, holds supreme stature with its pharmaceutical association in treating various ailments, particularly in Ayurvedic medicine. The present study aimed to evaluate the response of E. alba plants exposed to ambient (AT) and two different supplemental UV-B doses (eUV-B, ambient ±7.2 kJ m-2 day-1), i.e., intermittent (IT) and continuous (CT) UV-B treatment for 130 and 240 h respectively. Antioxidative activities and medicinally important compounds (wedelolactone) were measured in different plants' parts at three growth stages. Under both the eUV-B treatments, the photosynthetic pigments were adversely affected (along with reductions in protein content) with a concomitant increase in secondary metabolites. Substantial variations in enzymatic antioxidants and non-enzymatic compounds showed the adaptive resilience strategies of plants against eUV-B. The wedelolactone content increased in leaves but compromised in stem and roots under IT. The results concluded that IT UV-B exposure led to the improvement of plant growth and the yield of wedelolactone compared to CT, suggesting its ameliorative role in improving the test plant's medicinal value.

Population pharmacokinetics and Monte Carlo simulation for dosage optimization of fosfomycin in the treatment of osteoarticular infections in patients without renal dysfunction.

Background: Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens.Objective: The aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16g/daily by intermittent (II) or continuous infusion (CI), and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections.Methods: Patients underwent blood sampling on day 5 of therapy (2-3 serial samples). Population pharmacokinetics and Monte Carlo simulations were performed to define the probability of target attainment (PTA) of 70% T>MIC, and the cumulative fraction of response (CFR) against common OI pathogens with dosages of 8, 12, 16, and 20g/day administered by II, extended-infusion (EI) or CI.Results: Forty-eight patients were recruited. A two-compartment open model with infusion input and first-order elimination was developed. Estimated creatinine clearance (CLCR) was included as covariate in the final model. Monte Carlo simulations showed that optimal PTAs and CFRs (≥90%) may be achieved in three different classes of renal function by administering a daily dosage of: 2g q6h by II against S. aureus, E. coli, ESBL-producing E. Coli and MRSA; 8g by CI against CoNS, K. pneumoniae and ESBL-producing K. pneumoniae; 12g by CI against P. aeruginosa, and 16g by CI against KPC-producing K. pneumoniae Conclusion: Our study provides a strong rationale for considering fosfomycin dosages of 8-16 g daily by CI in several clinical scenarios for OI patients. Feasibility of administration by CI in an elastomeric pump makes fosfomycin a candidate for OPAT programs.

Greater decrements in neuromuscular function following interval compared to continuous eccentric cycling

Our aim was to determine the demands and consequences of a single session of continuous (CONT) or interval (INT) eccentric cycling. Fourteen healthy males performed ‘work-matched’ CONT and INT eccentric cycling in a cross over design. Measures of maximal voluntary contraction (MVC), resting twitch force, voluntary activation (VA), muscle soreness and creatine kinase (CK) were taken at baseline, immediately post, and 24, 48 and 72 h post the first exercise bout. The second bout was used to characterise within session demands. Decreases in MVC (INT 19%, CONT 13%), twitch force (INT 31%, CONT 18%), and VA (INT 10%, CONT 6%) were observed immediately post session (p < 0.05). Reductions in twitch force were greater after INT (p < 0.05) and lasted 48 h. Muscle soreness was greater following INT, versus CONT (p < 0.05), although no differences in CK were observed. Metabolic demands (% of V̇O2peak and [BLa]) were greater during INT vs. CONT (32 ± 6% 28 ± 6%; p < 0.001), [BLa] (1.0 ± 0.4 vs. 0.8 ± 0.2 mmol·L−1; p < 0.001) and RPE (12 ± 1 vs. 11 ± 1; p < 0.001), respectively. Total time under tension was 48% greater in CONT compared to INT (p < 0.001), whereas average torque (during exercise) was 40% greater during INT compared to CONT (p < 0.001). Interval eccentric cycling exacerbates muscle soreness, decrements in muscle function and lengthens recovery compared to a work matched continuous bout, which is attributable to increased force rather than time under tension.

Intermittent endoscopic ultrasound guided fine-needle aspiration for the diagnosis of solid pancreatic lesions. A pilot study.

endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is the method of choice for sampling pancreatic solid lesions. However, there is significant heterogeneity in terms of the technique used. Intermittent aspiration has not been evaluated in pancreatic solid lesions and could improve the diagnostic performance. a single-blind, non-inferiority pilot study was performed. Patients with solid pancreatic lesions and an indication for EUS-FNA were prospectively included. Patients were randomly assigned to intermittent (IS) or continuous (CS) suction techniques. Diagnostic performance, cellularity, blood contamination and the number of passes required to reach a diagnosis were evaluated. thirty-three patients were assigned to CS (16 patients) or IS (17 patients). Diagnostic performance was 87.5 % for CS and 94.1 % for IS (OR 2.29, 95 % CI: 0.19-27.99, p = 0.51). In the IS group, samples had a higher cellularity (OR 1.83, 95 % CI: 0.48-6.91, p = 0.37) and lower blood contamination (OR 0.38, 95 % CI: 0.09-1.54, p = 0.18). The number of passes required to reach a diagnosis was 2.12 for CS and 1.94 for IS (p = 0.64). Liquid cytology was obtained in 73.3 % of IS and 61.5 % of CS (OR 1.72, 95 % CI: 0.35-8.50). the IS technique was not inferior to CS in terms of diagnostic accuracy in the evaluation of pancreatic solid lesions, with a tendency to obtain higher cellularity, lower blood contamination and the frequent presence of cell block.

Self-Selected Versus Standardised Warm-Ups; Physiological Response on 500 m Sprint Kayak Performance.

This study investigated the effectiveness of a self-selected (SS) warm-up on 500 m sprint kayak performance (K500) compared to continuous (CON) and intermittent high intensity (INT)-type warm-ups. Twelve nationally ranked sprint kayakers (age 17.7 ± 2.3 years, mass 69.2 ± 10.8 kg) performed CON (15 min at the power at 2 m·mol−1), INT (10 min at 2 m·mol−1, followed by 5 × 10 s sprints at 200% power at VO2max with 50 s recovery at 55% power at VO2max), and SS (athlete’s normal competition warm-up) warm-ups in a randomised order. After a five-minute passive recovery, K500 performance was determined on a kayak ergometer. Heart rate and blood lactate (BLa) were recorded before and immediately after each warm-up and K500 performance. Ratings of perceived exertion (RPE) were recorded at the end of the warm-up and K500. BLa, heart rate, and RPE were generally higher after the INT than CON and SS warm-ups (p < 0.05). No differences in these parameters were found between the conditions for the time trial (p > 0.05). RPE and changes in BLa and heart rate after the K500 were comparable. There were no differences in K500 performance after the CON, SS, or INT warm-ups. Applied practitioners can, therefore, attain similar performance independent of warm-up type.

Treatment-Free Intervals Mitigate T-Cell Exhaustion Induced By Continuous CD19xCD3-BiTE® Construct Stimulation in Vitro

The bispecific T-cell engager (BiTE®) blinatumomab is approved for treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia and applied as continuous infusion over 28 days. The overall response rate to blinatumomab reported in clinical trials was 43 % and correlated to T-cell expansion (Zugmaier et al. 2015). In chronic viral infections, continuous antigen stimulation induces T-cell exhaustion, defined by phenotypic changes and functional impairment (Wherry 2011). Thus, we hypothesized that continuous BiTE® construct stimulation leads to T-cell exhaustion and that a treatment-free interval (TFI) reverses progressive T-cell dysfunction. To simulate continuous application of a BiTE® construct in vitro, T-cell long-term co-cultures were set up. Healthy donor T cells were stimulated in the presence of CD19+ OCI-Ly1 cells for 28 days with AMG 562, a half-life extended CD19 and CD3 specific BiTE® construct. T cells were harvested from the co-culture every 3-4 days between day 7 and 28 and assessed for markers of T-cell exhaustion: (1) AMG 562-mediated cytotoxicity of T cells was evaluated as specific lysis of CD19+ Ba/F3 target cells after 3 days, (2) T-cell expansion during the cytotoxicity assay was calculated as fold change (FC) of CD2+ counts, (3) Cytokine secretion of AMG 562-stimulated T cells was evaluated in co-culture supernatants by cytometric bead array (CBA) or after PMA/Ionomycine stimulation via intracellular cytokine staining (ICCS), (4) T-cell metabolic fitness was determined by Mito- and Glycolytic Stress Test using a Seahorse Analyzer, and (5) expression of the exhaustion-related transcription factor TOX was assessed by multiparameter flow cytometry. In order to assess the effect of a TFI on T-cell function, we cultured T cells and CD19+ OCI-Ly1 cells in the absence of AMG 562 from day 7-14 and 21-28 and compared their activity to T cells stimulated continuously with AMG 562. On day 7 of continuous (CONT) AMG 562 stimulation, we observed high cytotoxic and proliferative potential (% specific lysis=93±0.2, FC=2.9±0.2) as well as high IFN-g and TNF-a secretion analyzed by ICCS (% CD8+IFN-g+TNF-a+=23±6.7). However, cytotoxicity and proliferation decreased gradually until day 28 (% specific lysis=28±8.9; FC=0.6±0.1). CBA analysis confirmed decreasing secretion of IFN-g (day 3: 61113±12482, day 24: 3085±1351 pg/ml) and TNF-a (day 3: 1160±567, day 24: 43±7.6 pg/ml) as well as decreased IL-2 and granzyme B levels in culture supernatants. We furthermore observed highest mitochondrial fitness and basal glycolysis in T cells on day 7 of stimulation (basal OCR=2.2±0.6, maximal OCR=3.7±1.0, SRC=1.5±1.1 pmol/min/1000 cells, basal ECAR=2.0±0.4 mpH/min/1000 cells) which decreased until day 28 (basal OCR=0.4±0.2, maximal OCR=1.5±0.5, SRC=1.0±0.2 pmol/min/1000 cells, basal ECAR=0.5±0.2 mpH/min/1000 cells). In concordance, TOX increased during continuous stimulation (MFI ratio CD8+ day 7=6±0.8 to 12±0.8 on day 28). Strikingly, implementation of a TFI of 7 days led to superior cytotoxicity in T cells compared to continuously stimulated T cells (% specific lysis on day 14 CONT=34±4.2, TFI=99±2.2) and granzyme B production (CD8+; MFI ratio on day 14 CONT=124±11, TFI=303±34). Furthermore, increased proliferation during the cytotoxicity assay was observed in previously rested T cells (FC CONT=0.2±0.0, TFI=1.6±0.6). Although T cell function also decreased over time in TFI T cells, they maintained a strikingly higher cytotoxic potential (CONT=6±4.4, TFI=52±9.9) as well as higher granzyme B production (CONT=25±2, TFI=170±11) on day 28 compared to continuously stimulated T cells. In addition, TFI T cells showed increased IFN-g and TNF-a secretion after PMA/Ionomycine stimulation on day 28 (% CD8+IFN-g+TNF-a+ CONT=21±3.8, TFI=38±11.6). Our in vitro results demonstrate that continuous AMG 562 exposure negatively impacts T-cell function. Comprehensive analysis of T-cell activity in an array of functional assays suggests that continuous BiTE® construct exposure leads to T-cell exhaustion which can be mitigated through TFI. Currently, T cells from patients receiving blinatumomab are being analyzed to confirm the clinical relevance of our findings. Furthermore, RNA-Seq of continuously vs. intermittently AMG 562-exposed T cells will help us to understand underlying transcriptional mechanisms of BiTE® construct induced T-cell exhaustion. Disclosures Zieger: AMGEN Research Munich: Research Funding. Buecklein:Pfizer: Consultancy; Novartis: Research Funding; Celgene: Research Funding; Amgen: Consultancy; Gilead: Consultancy, Research Funding. Brauchle:AMGEN Inc.: Research Funding. Marcinek:AMGEN Research Munich: Research Funding. Kischel:AMGEN: Current Employment, Current equity holder in publicly-traded company, Patents &amp; Royalties. Subklewe:Gilead Sciences: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Morphosys: Research Funding; Seattle Genetics: Research Funding; AMGEN: Consultancy, Honoraria, Research Funding; Janssen: Consultancy; Roche AG: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Honoraria.

Continuous grazing of mixed native warm‐season grass in the fescue belt

AbstractContinuous, season‐long (May–August) grazing is the most commonly used grazing strategy among tall fescue [Lolium arundinaceum (Schreb.) Darbysh.] belt beef (Bos taurus) producers. However, little information is available regarding the feasibility of managing native warm‐season grass (NWSG) pastures in this region with continuous, season‐long grazing. We compared stand sustainability, beef cattle performance, and pasture production between continuous (CONT), season‐long grazing and heavy‐early (HEAVY), a modified continuous grazing strategy, on mixed‐NWSG pastures. Heavy‐early was designed to match the growth curve of NWSG, with an initial stocking target of 1.25 times the CONT density until 25 June, at which time stocking was reduced to 0.75 times the CONT density. Pastures were mixed big bluestem (Andropogon gerardii Vitman), indiangrass [Sorghastrum nutans (L.) Nash], and little bluestem [Schizachyrium scoparium (Michx.)]. The plant population (plants m−2) was similar between treatments, but years differed (P &lt; .001), with a 35% reduction from 2017, the third and final year of grazing, to 2018. Despite the decline in plant density, overall tiller density (tillers m−2) increased 14%, indicating that the grazing strategies were likely sustainable. The grazing strategies had similar (P &gt; .05) average daily gain (ADG; kg d−1), animal‐days ha−1, and total gain (kg ha−1). Weaned steer ADG was 0.98 kg d−1 for CONT and 0.89 kg d−1 for HEAVY. Total gain was 379 kg ha−1 for CONT and 334 kg ha−1 for HEAVY. Continuous grazing appears to be an appropriate strategy for managing NWSG pastures in the Fescue Belt.

A Comparison of Intermittent and Continuous Exercise Bouts at Different Intensities on Appetite and Postprandial Metabolic Responses in Healthy Men.

Exercise intensity affects many potential postprandial responses, but there is limited information on the influence of exercise modality. Therefore, the aim of this study was to investigate if the nature of exercise at two different intensities would affect gastric emptying rate (GER), appetite and metabolic responses following ingestion of a semi-solid meal. Twelve healthy men completed, in a random order, four 60-min cycles at 60% VO2peak (MOD), 40% VO2peak (LOW) and in a continuous (CON) or intermittent (INT) manner. INT consisted of 20 × 1-min exercise bouts with 2-min rest breaks. INT and CON were matched for total work output at each intensity. GER of the post-exercise meal was measured for 2 h using the 13C-breath method. Blood glucose, substrate utilisation and appetite ratings were measured at regular intervals throughout all trials and 24-h energy intake (EI) post-trials was assessed. GER-Delta over Baseline (DOB) was lower (p < 0.05) on MOD-INT vs. MOD-CON from 30–120 min post-meal. Blood glucose was higher mid-exercise (p < 0.05) on MOD-INT vs. MOD-CON. Although post-exercise LOW-CON was significantly higher than LOW-INT (p < 0.05), blood glucose was also higher 30-min post-meal ingestion on both CON trials compared to INT (p < 0.001). No interaction effect was observed for perceived appetite responses 2 h after meal ingestion (all p > 0.05). 24-h post-trial EI was similar between LOW-CON vs. LOW-INT (p > 0.05), although MOD-INT vs. MOD-CON 3500 ± 1419 vs. 2556 ± 989 kCal: p < 0.001 was elevated. In summary, MOD-INT exercise delays GER without stimulating perceived appetite in the 2 h period after meal ingestion, although EI was greater in the 24-h post-trial.

Tolerability and durable respones of the PI3Kδ inhibitor ME-401 administered on an intermittent schedule in relapsed/refractory (R/R) follicular lymphoma (FL) and other B-cell malignancies.

8016 Background: ME-401, a potent, selective, and structurally differentiated oral PI3kδ inhibitor was evaluated in a dose escalation/expansion Phase 1b study, and previously demonstrated a high objective response rate (ORR) in FL and chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) when given on a continuous (CS) or an intermittent schedule (IS). IS appeared to significantly reduce the incidence of immune-mediated adverse events of special interest (AESI) associated with PI3kδ inhibitors (diarrhea, rash, transaminase elevation, pneumonitis). We report maturing data from patients treated on the IS in this study. Methods: Eligible patients (pts) had FL, CLL/SLL, marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL), at least 1 prior therapy, adequate bone marrow and organs function, ECOG status ≤2, and no prior PI3K therapy. IS dosing: ME-401 at 60 mg/day for two 28-day cycles, followed by 7 days of therapy every 28-day cycle until disease progression or intolerance. Pts received ME-401 monotherapy (n = 21) or a combination with rituximab (n = 36) given at 375 mg/m2 for 8 doses in Cycles 1-6. Results: Total of 57 pts treated with IS: 35 FL, 10 CLL/SLL, 4 MZL, and 8 DLBCL with 38 (67%) currently still ongoing. Median age: 66 years (range 38-94) and median prior therapies: 2 (range 1-8). As of January 2020, median follow-up = 9.7 mo (range 0.6-25.4+). Grade 3 AESI reported in 7 pts: 2 diarrhea (3.5%), 2 colitis (3.5%), 1 rash (2%), 1 ALT increased (2%), and 1 pneumonitis (2%). No Grade 3 AESI reported beyond Cycle 3. Discontinuation for AE in 3 pts (5%). There were no discernable safety differences between the monotherapy and rituximab combination groups. ORR was 83% in FL (76% in monotherapy group, 88% in combination group) and 89 % in CLL/SLL (100%, 83%), with median duration of response not reached. Median PFS was not reached in all patients with FL and CLL (combined analysis of both single agent and with rituximab). ORR was 100% (4/4) in MZL and 25 % (2/8) in DLBCL (in combination group only). Conclusions: ME-401 administered on an IS was well-tolerated, with a low-rate of Grade 3 class-related AESI and achieved a high-rate of durable objective responses in R/R indolent B-cell malignancies. These results may differentiate ME-401 and support further evaluation as a single-agent and in combination regimens. An ongoing global trial is evaluating ME-401 by IS in pts with FL after failure of ≥2 prior therapies (NCT03768505). Clinical trial information: NCT02914938 .

Effect on essential oil components and wedelolactone content of a medicinal plant Eclipta alba due to modifications in the growth and morphology under different exposures of ultraviolet-B.

In the present study sensitivity of a medicinal plant Eclipta alba L. (Hassk) (False daisy) was assessed under intermittent (IT) and continuous (CT) doses of elevated ultraviolet-B (eUV-B). Eclipta alba is rich in medicinally important phytochemical constituents, used against several diseases. The hypothesis of this study is that alterations in UV-B dose may modify the quantity and quality of medicinally valuable components with changes in the morphological and physiological parameters of test plant. To fulfill our hypothesis IT and CT of eUV-B (ambient ± 7.2kJm-2day-2) was given for 130 and 240h respectively to assess the impact of UV-B stress. Growth and physiological parameters were adversely affected under both the treatments with varying magnitude. The observation of leaf surfaces showed increase in stomatal and trichome densities suggesting the adaptive resilience of the plants against UV-B. Besides, biosynthesis of wedelolactone, a major medicinal compound of E. alba was observed to be stimulated under UV-B exposure. The essential oil content was reduced under IT while increased under CT. A total of 114 compounds were identified from oil extract of E. alba. n-Pentadecane (25.79%), n-Octadecane (12.98%), β-Farnesene (9.43%), α-Humulene (4.95%) (E)-Caryophyllene (4.87%), Phytol (4.25%), α-Copaene (2.26%), Humulene epoxide (1.46%), β-Pinene (1.07) and β-Caryophyllene oxide (1.06%) were identified as major components of oil. CT induced the synthesis of some medicinally important compounds such as α-terpineol, δ-cadinene, linolenic acid, methyl linoleate and myristic acid amide. Hence, the study revealed that continuous UV-B exposure of low intensity could be helpful for commercial exploitation of essential oil in E. alba.

Impact of Short-Term Continuous and Interval Exercise Training on Endothelial Function and Glucose Metabolism in Prediabetes.

Introduction The impact of interval (INT) vs. continuous (CONT) exercise training on endothelial function in relation to glucose metabolism prior to clinically meaningful weight loss is unknown in adults with prediabetes. Methods Twenty-six subjects with prediabetes (60 ± 1 y; 33 ± 1 kg/m2; 2-hr-PG OGTT: 145 ± 7 mg/dl) were randomized to 60 min of CONT (n = 12; 70% of HRpeak) or work-matched INT exercise training (n = 14; alternating 3 min at 90 and 50% HRpeak) for 2 weeks. Aerobic fitness (VO2peak) and body composition (bioelectrical impedance) were assessed before and after training. Flow-mediated dilation (FMD) was measured during a 2 h 75 g OGTT (0, 60, and 120 min) to assess endothelial function. Postprandial FMD was calculated as incremental area under the curve (iAUC). Glucose tolerance and insulin were also calculated by iAUC. Fasting plasma VCAM, ICAM, and hs-CRP were also assessed as indicators of vascular/systemic inflammation. Results Both interventions increased VO2peak (P = 0.002) but had no effect on body fat (P = 0.20). Although both treatments improved glucose tolerance (P = 0.06) and insulin iAUC (P = 0.02), VCAM increased (P = 0.01). There was no effect of either treatment on ICAM, hs-CRP, or fasting as well as postprandial FMD. However, 57% of people improved fasting and iAUC FMD following CONT compared with only 42% after INT exercise (each: P = 0.04). Elevated VCAM was linked to blunted fasting FMD after training (r = −0.38, P = 0.05). But, there was no correlation between fasting FMD or postprandial FMD with glucose tolerance (r = 0.17, P = 0.39 and r = 0.02, P = 0.90, respectively) or insulin iAUC following training (r = 0.34, P = 0.08 and r = 0.04, P = 0.83, respectively). Conclusion Endothelial function is not improved consistently after short-term training, despite improvements in glucose and insulin responses to the OGTT in obese adults with prediabetes.

The Effects of Interval and Continuous Training on the Oxygen Cost of Running in Recreational Runners: A Systematic Review and Meta-analysis.

Oxygen cost of running is largely influenced by endurance training strategies, including interval and continuous training. However, which training method better reduces the oxygen cost remains unknown. This study aimed to systematically review the scientific literature and performs a meta-analysis to address the effects of different endurance training modalities on the oxygen cost of running. A literature search on 3 databases (MEDLINE, SPORTDiscus and Web of Science) was conducted on February 28, 2019. After analysing 8028 resultant articles, studies were included if they met the following inclusion criteria: (a) studies were randomised controlled trials, (b) studies included trained runners without previous injuries (c) interventions lasted at least 6weeks, with participants allocated to Interval (INT) or Continuous (CON) groups, and (d) oxygen cost was assessed pre- and post-training intervention. Six studies (seven trials) met the inclusion criteria and were included in the meta-analysis. This resulted in 295 participants (n = 200 INT; n = 95 CON training method). Standardised mean difference with 95% confidence intervals (CI) between INT and CON conditions and effect sizes were calculated. To assess the potential effects of moderator variables (such as, age, VO2max of participants, number of weeks of intervention) on main outcome (oxygen cost of running), subgroup analyses were performed. Comparing changes from pre- to post-intervention, oxygen cost improved to a greater extent in CON when compared to INT interventions (0.28 [95% CI 0.01, 0.54], Z = 2.05, p = 0.04, I2 = 30%). Oxygen cost improvements were larger in participants with higher VO2max (≥ 52.3mlkg-1min-1) (0.39 [95% CI 0.06, 0.72], Z = 2.34, p = 0.02), andin programs greater or equal to 8weeks (0.35 [95% CI 0.03, 0.67], Z = 2.13, p = 0.03). When the total volume per week of INT was ≥ 23.2min, there was a significant improvement favorable to CON (0.34 [95% CI 0.01, 0.61], Z = 2.02, p = 0.04). Continuous training seems, overall, a better strategy than interval training to reduce the oxygen cost in recreational endurance runners. However, oxygen cost reductions are influenced by several variables including the duration of the program, runners' aerobic capacity, the intervals duration and the volume of interval training per week. Practitioners and coaches should construct training programs that include both endurance training methods shown to be effective in reducing the oxygen cost of running.

Interval Exercise Lowers Circulating CD105 Extracellular Vesicles in Prediabetes.

Extracellular vesicles (EV) are purported to mediate type 2 diabetes and CVD risk and development. Physical activity and a balanced diet reduce disease risk, but no study has tested the hypothesis that short-term interval (INT) training would reduce EV compared with continuous (CONT) exercise in adults with prediabetes. Eighteen obese adults (age, 63.8 ± 1.5 yr; body mass index, 31.0 ± 1.3 kg·m) were screened for prediabetes using American Diabetes Association criteria (75 g oral glucose tolerance test). Subjects were randomized to INT (n = 10, alternating 3-min intervals at 90% and 50% HRpeak, respectively) or CONT (n = 8, 70% HRpeak) training for 12 supervised sessions over 13 d for 60 min·d. Cardiorespiratory fitness (V˙ O2peak), weight (kg), as well as ad libitum dietary intake were assessed and arterial stiffness (augmentation index via applanation tonometry) was calculated using total AUC during a 75-g oral glucose tolerance test performed 24 h after the last exercise bout. Total EV, platelet EV (CD31/CD41), endothelial EV (CD105; CD31/ CD41), platelet endothelial cell adhesion molecule (PECAM) (CD31), and leukocyte EV (CD45; CD45/CD41) were analyzed via imaging flow cytometry preintervention/postintervention. The INT exercise increased V˙O2peak (P = 0.04) compared with CONT training. Although training had no effect on platelet or leukocyte EV, INT decreased Annexin V- endothelial EV CD105 compared with CONT (P = 0.04). However, after accounting for dietary sugar intake, the intensity effect was lost (P = 0.18). Increased ad libitum dietary sugar intake after training was linked to elevated AV+ CD105 (r = 0.49, P = 0.06) and AV- CD45 (r = 0.59, P = 0.01). Nonetheless, increased V˙O2peak correlated with decreased AV+ CD105 (r = -0.60, P = 0.01). Interval exercise training decreases endothelial-derived EV in adults with prediabetes. Although increased sugar consumption may alter EV after a short-term exercise intervention, fitness modifies EV count.

In-exercise vascular shear rate during acute continuous and interval exercise: impact on endothelial function and miR-21.

Endothelial cell phenotype and endothelial function are regulated by hemodynamic forces, particularly wall shear stress (WSS). During a single bout of exercise, the specific exercise protocol can affect in-exercise WSS patterns and, consequently, endothelial function. MicroRNAs might provide a biomarker of in-exercise WSS pattern to indicate whether a specific exercise bout will have a positive effect on endothelial function. We evaluated the effect of acute interval (IT) and continuous (CON) in-exercise WSS patterns upon postexercise endothelial function and circulating microRNA (miR)-21 expression. Methods and results: 13 participants performed CON and 3 different IT exercise protocols matched for duration and intensity on separate days. Oxygen uptake, heart rate, and brachial artery blood flow were recorded throughout the exercise. Brachial artery flow-mediated dilation (FMD) was performed pre-exercise and 15 min postexercise. Plasma samples were acquired pre-exercise and 6 h postexercise to determine miR-21 expression. In-exercise shear rate (SR) patterns (a surrogate of WSS) differed according to the CON or IT work-rate profile. In-exercise anterograde SR was greater in CON than IT exercise (P < 0.05), but retrograde SR was equivalent between exercise protocols (P > 0.05). Oscillatory shear index was higher during IT versus CON exercise (P < 0.05). Postexercise FMD increased (pre: 7.08% ± 2.95%, post: 10.54% ± 4.24%, P < 0.05), whereas miR-21 expression was unchanged (pre: 12.0% ± 20.7% cel-miR-39, post: 11.1 ± 19.3% cel-miR-39, P > 0.05) with no effect of exercise protocol (P > 0.05). Conclusions: CON and IT exercise induced different SR patterns but equivalent improvements in acute endothelial function. The absence of change in miR-21 expression suggests that miR-21 is not a suitable biomarker of exercise-induced SR.NEW & NOTEWORTHY Interval exercise has the potential to negatively impact vascular adaptations because of repeated oscillations in vascular shear. To our knowledge, we are the first to continuously assess exercise-induced shear throughout different acute exercise protocols and examine its relationship with acute endothelial function and a circulating biomarker of shear (miR-21). These experiments provide clear data indicating enhancement of the acute vascular response from differing interval exercise protocols, with the study also providing detailed vascular and shear responses for future reference.

Using Continuous And Interval Exercise To Manipulate Shear Rate Patterns In The Common Femoral Artery

Vascular shear rate (SR) assessed via ultrasound represents frictional force of blood flowing over the endothelium. Low and oscillatory shear confers a pro-inflammatory phenotype, whereas greater shear has an anti-inflammatory phenotype decreasing CVD risk. Exercise increases SR, however the impact of continuous (CON) and interval (INT) exercise upon the balance of anterograde (ANT) and retrograde (RET) SR and thus the oscillatory shear index (OSI) is unknown. PURPOSE: To examine the impact of acute CON and INT (no active recovery) exercise on SR patterns and OSI in the common femoral artery (CFA) during exercise. METHODS: 10 healthy individuals (25±3 years, n=5 male) underwent two work-matched exercise sessions (CON and INT) on a supine cycle ergometer at 125% lactate threshold. In each protocol repetitive ultrasound scans were taken of the CFA during a brief cessation in exercise to determine in-exercise shears. Flow mediated dilatation (FMD) was measured before and after exercise to assess acute changes in endothelial function. RESULTS: FMD did not differ after exercise in either protocol (CON: 9.9±8.1% vs 8.4±6.2%; INT: 9.1±5.9% vs 6.6±3.4%: P>0.05). ANT and RET SR reached a plateau in each protocol. Total ANT SR was lower in CON than INT (CON: 861540±291534 vs INT: 1955615±674594 s-1: P<0.05), however total RET SR did not differ between protocols (CON: 76625±89390 vs INT: 78126±78697 s-1: P>0.05). Peak and mean SR were similar in CON and INT, respectively (peak ANT: 1258±403 vs 1480±510 s-1; RET: 107±123 vs 108±75 s-1: P>0.05; meanANT: 1171±372 vs 1358±469 s-1; RET: 61±81 vs 54±55 s-1: P>0.05). Mean and peak OSI were also similar in both types of exercise (peak CON: 0.07±0.08 vs INT: 0.08±0.0.06 AU; mean CON: 0.05±0.06 vs INT: 0.04±0.04 AU; P>0.05). No time was spent in pure oscillatory shear (>0.5 AU). CONCLUSION: During exercise matched for intensity and the duration of muscular work, using an INT approach ensured a similar OSI but a greater total ANT SR compared to CON. This would suggest that in the exercising limb INT exercise does not confer a negative oscillatory profile. GRANT FUNDING: Medical Research Council

Acute High-Intensity Interval Exercise in Multiple Sclerosis with Mobility Disability.

Multiple sclerosis (MS) is an immune-mediated, neurological disease that results in physiological deconditioning with increasing disability. High-intensity interval training (HIIT) exercise has induced significant improvements in physiological conditioning in healthy and clinical populations and might be appropriate for persons with MS who have mobility disability. The feasibility and acute effects of HIIT using recumbent stepping in persons with MS who have mobility disability are relatively unknown. The physiological effects of single sessions of HIIT and continuous (CON), steady-state aerobic exercise using recumbent stepping were compared in 20 persons with MS with mobility disability (i.e., Expanded Disability Status Scale of 4.0-6.5). The HIIT bout included 10 cycles of 1-min intervals at the work rate associated with 90% peak aerobic capacity (V˙O2peak) followed by 1-min recovery intervals at 15 W, totaling 20 min in length. The CON bout consisted of 20 min at the work rate associated with 50% to 60% V˙O2peak. Physiological (i.e., power output, oxygen consumption, carbon dioxide expiration, respiratory exchange ratio, ventilation, HR, and core temperature) and perceptual (i.e., ratings of perceived exertion) measures were collected across the acute sessions. There were statistically significant condition-time interactions for all physiological measures and ratings of perceived exertion expressing differential patterns of change over time for HIIT versus CON (P < 0.05). The main effect of condition was significant for all physiological outcomes, except core temperature, with the HIIT condition inducing significantly higher values than CON (P < 0.05). High-intensity interval training exercise taxes the cardiorespiratory system significantly more than CON, yet without deleterious effects on core temperature in persons with MS. This has important implications for informing an evidence-based exercise prescription that is appropriate for improving physiological conditioning in persons with MS who have mobility disabilities.

Intermittent tinnitus-an empirical description.

Tinnitus is often classified into acute or chronic persistent forms. However, epidemiologic studies have shown that intermittent tinnitus (IT), which does not clearly belong to either category, is the most common form. The aim of this study was to further characterize IT empirically. We conducted an exploratory cross-sectional interview study among 320 subjects with tinnitus. Sociodemographic and tinnitus characteristics, concomitant complaints, perceived triggers, and help-seeking behavior were assessed. Subjects were classified into continuous (CT), IT, or single-episode tinnitus (SET) if they had experienced tinnitus "continuously," "temporarily time and again," or "only once but for several days," respectively, during the past 12months. Of the sample, 62% reported IT, 23% SET, and 16% CT. Mean time since onset was 36(CT), 28(IT), and 19months (SET), respectively. Most subjects with IT experienced episodes lasting afew days, whereas in 25%, episodes lasted 1-4weeks. Mean duration was 1.6weeks. The frequency of IT episodes ranged from every few days to half-yearly; mean frequency was every 7weeks. Leading triggers were occupational and private stress. Asthenia, depression, social isolation, psychiatric disorders, and inner ear disorders were more prevalent among CT than IT subjects. Help-seeking behavior was comparable between CT and IT. IT is associated with emotional reactions and situational impairment severe enough to trigger multiple treatment attempts, but usually does not result in severe impairment. Inner ear disorders and psychological changes are less frequent than in CT; therefore, treatment response and prognosis might be better. We suggest classification of tinnitus into acute single-episode (<3months), intermittent, or chronic persistent (>3months) forms.

Effects of grazing system, season, and forage carbohydrates on glucose and insulin dynamics of the grazing horse.

Rotational grazing is a recommended practice for grazing livestock, but little is known about its benefits with respect to grazing horses. The objective of this study was to investigate the effects of continuous (CON) and rotational (ROT) grazing on forage nutrient composition and whether those concentrations influenced circulating glucose and insulin concentrations in the grazing horse. Twelve mature Standardbred mares were paired by age and weight and randomly assigned to 1 replicate of either a 1.5 ha cool-season grass CON or ROT system for a total of 3 mares in each system. Mares on CON were allowed to graze the entire system at all times, whereas mares on ROT were given access to a 0.4 ha pasture section and stress lot where they were confined during inclement weather and slow forage growth. Blood and feces from horses and forage from each system were sampled over one 24-h period in June, August, and October. Blood was assessed for plasma glucose (GLU) and serum insulin (INS), feces for pH, and forage for nutritional composition. Data were analyzed by ANOVA with repeated measures with significance set at P < 0.05. There were no treatment differences for water and ethanol soluble carbohydrates (WSC and ESC, respectively), starch, ADF, and NDF, but CP was lower in ROT compared to CON (P = 0.04). With respect to month, WSC were highest in June compared to August and October, whereas ESC were highest in June compared to only August. Starch was lower in October than in June and August. Concentrations of ADF and NDF were lowest in October compared to June and August. Crude protein was higher in October than June and August. Plasma GLU and serum INS were affected by season and time of day but not grazing system. For all horses, GLU was highest in August (105.6 ± 1.3 mg/dL), whereas INS was highest in October (0.21 ± 0.02 μg/L; P < 0.0001). Fecal pH only varied by season and was highest in August (7.06; P < 0.0001). Few consistent correlations between grazing systems were found with the exception of INS with ESC (R = 0.32 to 0.39; P < 0.04) and INS and GLU with ADF and NDF in August and October (R = -0.31 to -0.48; P < 0.04). In conclusion, grazing system did not affect the forage carbohydrate concentrations or GLU or INS in horses; however, season did have an effect on both forage nutrient content and glucose metabolism in horses.

Intermittent tinnitus-an empirical description. German version

Tinnitus is often classified into acute or chronic persistent forms. However, epidemiologic studies have shown that intermittent tinnitus (IT), which does not clearly belong to either category, is the most common form. The aim of this study was to further characterize IT empirically. We conducted an exploratory cross-sectional interview study among 320 subjects with tinnitus. Sociodemographic and tinnitus characteristics, concomitant complaints, perceived triggers, and help-seeking behavior were assessed. Subjects were classified into continuous (CT), IT, or single-episode tinnitus (SET) if they had experienced tinnitus "continuously," "temporarily time and again," or "only once but for several days," respectively, during the past 12months. Of the sample, 62% reported IT, 23% SET, and 16% CT. Mean time since onset was 36(CT), 28(IT), and 19months (SET), respectively. Most subjects with IT experienced episodes lasting afew days, whereas in 25%, episodes lasted 1-4weeks. Mean duration was 1.6weeks. The frequency of IT episodes ranged from every few days to half-yearly; mean frequency was every 7weeks. Leading triggers were occupational and private stress. Asthenia, depression, social isolation, psychiatric disorders, and inner ear disorders were more prevalent among CT than IT subjects. Help-seeking behavior was comparable between CT and IT. IT is associated with emotional reactions and situational impairment severe enough to trigger multiple treatment attempts, but usually does not result in severe impairment. Inner ear disorders and psychological changes are less frequent than in CT; therefore, treatment response and prognosis might be better. We suggest classification of tinnitus into acute single-episode (<3months), intermittent, or chronic persistent (>3months) forms.