Crossover Design Research Articles

The Cognitive Function and Taekwondo-Specific Kick Performance of Taekwondo Athletes at Different Hydration Statuses.

Successful participation in taekwondo (TKD) requires athletes to possess quick decision-making abilities and demonstrate technical proficiency during competition. Dehydration, occurring during both training and competition, is widely recognized to have various negative effects. This study investigated the impact of different levels of dehydration on cognitive function, as measured by the Vienna Test System, and the specific performance of kicking techniques among TKD athletes. Using a randomized crossover design, 12 participants were involved in the study. Before and after 1 hour of training at 80% of maximal heart rate, participants were weighed and provided urine samples. All participants were randomly assigned to 3 different hydration conditions: the euhydrated (EUH) group had unrestricted access to fluid consumption, while the hypohydrated (HYP) and severelyHYP (S-HYP) groups experienced reductions of 2.0% and 4.0% of their initial body weight, respectively. The EUH group exhibited better reaction speed in reaction-time test-form S1 than the HYP and S-HYP groups. Notably, the EUH group demonstrated a significantly higher success rate in the front-side kick (EUH 98%, HYP 90%, S-HYP 88%; P < .05). However, the success rates of back roundhouse kick and free head kick were similar among the 3 statuses. Furthermore, postexercise heart rates were found to be significantly higher in the HYP and S-HYP groups compared with the EUH group. This study provides insight into the negative effects of dehydration on cognitive function and TKD-specific performance. It is recommended that TKD athletes maintain optimal hydration levels during training and competition to ensure optimal performance.

Enhancing Flexibility through Chinese Auriculotherapy: Investigating the Impact on Sit and Reach Test – A Randomized Controlled Trial

Chinese auriculotherapy (CA) is a technique that is part of acupuncture and traditional Chinese medicine (TCM). Acupuncture techniques have been utilized in physical practices to enhance performance and manage pain. Nevertheless, it remains uncertain whether CA can enhance performance in stretching exercises. Thus, this study aims to determine if CA can have an ergogenic effect on the sit and reach test and to evaluate the impact of CA on pain perception and effort during the test. Our hypotheses is that CA will positively influence performance in the sit and reach test by reducing pain perception through the implemented protocol. The study employed a randomized, double-blind, crossover design. The sample consisted of 15 individuals (12 women and 3 men, mean age 22.33 ± 6.4 years, BMI 23.43 ± 4.24). The participants underwent a flexibility assessment protocol using the sit and reach test under three different conditions: I) CA protocol; II) CA placebo protocol (CAP); III) control group without any therapeutic intervention (CG). Subjective pain and effort perception were evaluated using the CR-10 Borg scale. A statistical difference was observed between CA vs. CAP and CA vs. CG in the sit and reach test. No statistical changes were found for the other variables and conditions studied. A significance level of 5% was adopted. Therefore, CA can enhance performance in the sit and reach test; however, the mechanisms responsible for this improvement are still unclear.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction ( P &lt;0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P =0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov ; Unique Identifier: NCT03450252.

Equivalence, modality use and patient satisfaction of telepractice administration of the scenario test in persons with primary progressive aphasia

BACKGROUND: The use of telediagnostics for people with primary progressive aphasia (PPA) could improve access to specialised care. There is a gap in research, especially regarding to the evaluation of communicative-pragmatic measurement tools in a digital setting. OBJECTIVE: This study examined the equivalence, modality use, and patient satisfaction of telepractice administration of the Scenario Test (ST) in people with PPA. METHODS: In a cross-over design, the ST was conducted once by videoconferencing and once in person. Fifteen people with PPA participated. Participant satisfaction was assessed after each test session using a short self-designed questionnaire. The total ST scores, the use of the different communicative modalities and the participant satisfaction scores were evaluated using the equivalence and McNemar test. RESULTS: Statistical equivalence was established for the present sample with regard to the total score of the ST. Regarding the use of the different modalities, no significant difference was found. Sample satisfaction was positive for both diagnostic settings, but there was no statistical equivalence of satisfaction. Severe psychiatric and cognitive symptoms affected the test performance. CONCLUSIONS: This study highlights opportunities and limitations of telepractice administration of the ST in people with PPA. There is some evidence that testing with the ST via videoconferencing is feasible. Differences in the use of communication modalities and participant satisfaction should be further investigated. Influencing factors such as psychiatric symptoms and cognitive deficits should be considered in future research projects.

Acute effects of static stretching exercise-induced decrease in arterial stiffness on maximal aerobic capacity.

We recently have reported that individual day-to-day arterial stiffness variations are associated with maximal aerobic capacity. However, the evidence of this phenomenon was not provided sufficiently. The present study aimed to examine whether a decrease in arterial stiffness through static stretching exercise could enhance maximal aerobic capacity. Twelve healthy young men (age 22±2 years, mean and standard deviation) participated in this study and underwent two separate sessions in a randomized controlled crossover design: a single session of a whole-body static stretching exercise protocol that involved the trunk, upper limb, and lower limb (stretch condition), and sedentary control where they rested in the exercise room. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of systemic arterial stiffness before, immediately after and at 30 min after both conditions. Maximal oxygen uptake (V̇O<inf>2</inf>max) was assessed using a graded power test on an electronically braked cycle ergometer after these measurements. As we expected, there was a significant decrease in the baPWV at 30 min after the stretch trial compared to baseline values (P=0.01). The baPWV in the stretch condition was lower than that of the control condition, while V̇O<inf>2</inf>max in the stretch condition was higher than that of the control condition (P=0.03). Based on these findings, it can be inferred that an acute reduction in arterial stiffness may contribute to change in maximal aerobic capacity.

An Efficient Way to Find Optimal Crossover Designs Using CVX for Precision Medicine

Crossover designs play an increasingly important role in precision medicine. We show the search of an optimal crossover design can be formulated as a convex optimization problem and convex optimization tools, such as CVX, can be directly used to search for an optimal crossover design. We first demonstrate how to transform crossover design problems into convex optimization problems and show CVX can effortlessly find optimal crossover designs that coincide with a few theoretical crossover optimal designs in the literature. The proposed approach is especially useful when it becomes problematic to construct optimal designs analytically for complicated models. We then apply CVX to find crossover designs for models with auto-correlated error structures or when the information matrices may be singular and analytical answers are unavailable. We also construct N-of-1 trials frequently used in precision medicine to estimate treatment effects on the individuals or to estimate average treatment effects, including finding dual-objective optimal crossover designs.

Acute Upper-Body and Lower-Body Neuromuscular Fatigue Effect on Baseball Pitchers' Velocity: A Pilot Study.

Tremblay, M, Anderson Sirois, S, Verville, W, Auger, M, Abboud, J, and Descarreaux, M. Acute upper-body and lower-body neuromuscular fatigue effect on baseball pitchers' velocity: A pilot study. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this pilot study was to explore the acute effect of upper-body and lower-body neuromuscular fatigue protocols on baseball pitchers' velocity. Sixteen baseball pitchers were recruited, and a crossover design was used to meet the study purpose. Pitchers were tested twice, 7 days apart, with their upper-body and lower-body explosiveness, pitching velocity, and muscle soreness perception of their throwing arm (forearm flexors, biceps, anterior deltoid, and upper trapezius muscles) assessed before and after an upper-body and lower-body neuromuscular fatigue protocol. Two-way analysis of variances and paired t tests (p < 0.05) were used to identify and compare prescores and postscores. Following both fatigue protocols, results revealed a significant decrease in time for pitching velocity (p = 0.005, ηp2 = 0.462), and increases in muscle soreness perception of the forearm flexors (p = 0.005, ηp2 = 0.470), anterior deltoid (p = 0.045, ηp2 = 0.274), and upper trapezius (p = 0.023, ηp2 = 0.339) muscles. Paired t test results showed a significant decrease in preneuromuscular and postneuromuscular fatigue protocol in the upper-body (p < 0.01) and lower-body (p < 0.01) explosiveness scores. These pilot study results show the impact of different exercise protocols on pitchers' explosiveness, velocity, and muscle soreness perception emphasizing the need for further investigation into the acute effect of exercise targeting the upper or lower-body on pitching performance, specifically at the pitcher's position.

Timing matters: diurnal variation of maximal fat oxidation and substrate oxidation rates in metabolic syndrome-a randomized crossover study.

The aim of this study was to investigate if diurnal oscillation in maximal fat oxidation (MFO) and substrate oxidation rates during exercise exists in subjects with metabolic syndrome (MetS). In a randomized crossover design, 14 MetS patients were assigned to two graded exercise tests conditions performed in the morning (between 7:00 and 9:00 a.m) and in the afternoon (between 4:00 and 5:00 p.m). MFO was defined as the highest absolute value of fat oxidation obtained from the average of last 2-min stages during an indirect calorimetry test. MFO increased by 20.6% from morning to afternoon (p = 0.0002, Cohen's d = 0.52). There was a significant time of day, (p < 0.0001, η2p = 0.76) and intensity effect (p = 0.002, η2p = 0.32) in fat oxidation (Fatox) rates indicating that Fatox was higher in the afternoon than in the morning. Our study extends previous findings on the existence of diurnal variation in maximal fat oxidation to MetS patients, highlighting the afternoon as a more favorable time for fat utilization during exercise. These findings have practical implications for optimizing training timing in MetS patients. PACTR202306776991260.

Population Pharmacokinetics and Absolute Oral Bioavailability of Lasalocid after Single Intravenous and Intracrop Administration in Laying Hens.

Lasalocid sodium is a polyether carboxylic ionophore agent authorized by the EU for use as a coccidiostat in broilers, turkeys, and pullets up to 16 weeks of age, except for laying hens. However, laying hens are the most common nontarget species exposed to lasalocid sodium, mainly due to cross-contamination from feed mills. This exposure may result in potential drug residue deposition in eggs, which could potentially expose consumers to the drug. The breeds commonly used for commercial egg production in Poland are Isa Brown and Green-legged Partridge hens, which have been found to significantly differ in egg-laying performance. This variability may also affect the pharmacokinetics of lasalocid. Data on lasalocid plasma pharmacokinetics in laying hens are lacking. In this study, we aimed to determine typical population pharmacokinetic parameters, absolute oral bioavailability, and how breed may influence the pharmacokinetics of lasalocid. Twenty-layer hens of the two breeds were used in this study. Lasalocid was administered orally at a single dose of either 1 mg or 5 mg/kg body weight or intravenously at a dose of 1 mg/kg body weight, in a crossover design with a three-week washout period between study periods. Blood samples were collected for 72 h, and lasalocid concentrations were measured using high-performance liquid chromatography with fluorescence detection. A population pharmacokinetic analysis was conducted using nonlinear mixed effects modeling. Standard numerical and graphical criteria were used to select the best model, and a stepwise covariate modeling approach was used to determine any influencing factors. The best model was a three-compartment mammillary model with first-order absorption, transit compartments, and linear elimination. The estimated absolute oral bioavailability was low (36%). It was found that breed significantly influenced not only absorption but also the elimination of lasalocid. This study revealed that lasalocid absorption and elimination varied between the two breeds. This variability in pharmacokinetics may result in breed-related differences in drug residue accumulation in eggs, and ultimately, the risk associated with consumer exposure to drug residues may also vary.

Safety and effects of acetylated and butyrylated high amylose maize starch in recently diagnosed youths with type 1 diabetes; a Pilot Study.

Acetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic shown to be effective in type 1 diabetes (T1D) prevention in mouse models and is safe in adults with established T1D. HAMS-AB alters the gut microbiome profile with increased bacterial fermenters that produce short chain fatty acids (SCFAs) with anti-inflammatory and immune-modulatory effects. We performed a pilot study using a cross-over design to assess the safety and efficacy of 4 weeks of oral HAMS-AB consumption by recently diagnosed (< 2 years of diagnosis) youths with T1D. Seven individuals completed the study. The mean±SD age was 15.0±1.2 years, diabetes duration 19.5±6.3 months, 5/7 were female and 4/7 were White, all with a BMI of < 85th%. The prebiotic was safe. Following prebiotic intake, gut microbiome changes were seen, including a notable increase in the relative abundance of fermenters such as Bifidobacterium and Faecalibacterium. Treatment was also associated with changes in bacterial functional pathways associated with either improved energy metabolism (upregulation of tyrosine metabolism) or anti-inflammatory effects (reduced geraniol degradation). There were no differences in stool SCFA levels. Plasma metabolites associated with improved glycemia, such as hippurate, were significantly increased after treatment and there were positive and significant changes in the immune regulatory function of mucosal associated invariant T cells. There was a significant decrease in the area under the curve glucose but not C-peptide, as measured during a mixed meal tolerance testing, following the prebiotic consumption. In summary, the prebiotic HAMS-AB was safe in adolescents with T1D and showed promising effects on the gut microbiome composition, function and immune regulatory function.

Transcutaneous vagal nerve stimulation during lower body negative pressure

BackgroundPara-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP). Method10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded. ResultsOverall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05). ConclusiontVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

Systematic review for optimizing sample size in dairy cow methane emission studies in temperate regions: a comprehensive methodological approach.

This research introduces a systematic framework for calculating sample size in studies focusing on enteric methane (CH4, g/kg of DMI) yield reduction in dairy cows. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search across the Web of Science, Scopus, and PubMed Central databases for studies published from 2012 to 2023. The inclusion criteria were: studies reporting CH4 yield and its variability in dairy cows, employing specific experimental designs (Latin Square Design (LSD), Crossover Design, Randomized Complete Block Design (RCBD), and Repeated Measures Design) and measurement methods (Open-circuit respirometry chambers (RC), the GreenFeed system, and the sulfur hexafluoride tracer technique), conducted in Canada, the United States and Europe. A total of 150 studies, which included 177 reports, met our criteria and were included in the database. Our methodology for using the database for sample size calculations began by defining 6 CH4 yield reduction levels (5, 10, 15, 20, 30, and 50%). Utilizing an adjusted Cohen's f formula and a power analysis we calculated the sample sizes required for these reductions in balanced LSD and RCBD reports from studies involving 3 or 4 treatments. The results indicate that within-subject studies (i.e., LSD) require smaller sample sizes to detect CH4 yield reductions compared with between-subject studies (i.e., RCBD). Although experiments using RC typically require fewer individuals due to their higher accuracy, our results demonstrate that this expected advantage is not evident in reports from RCBD studies with 4 treatments. A key innovation of this research is the development of a web-based tool that simplifies the process of sample size calculation (samplesizecalculator.ucdavis.edu). Developed using Python, this tool leverages the extensive database to provide tailored sample size recommendations for specific experimental scenarios. It ensures that experiments are adequately powered to detect meaningful differences in CH4 emissions, thereby contributing to the scientific rigor of studies in this critical area of environmental and agricultural research. With its user-friendly interface and robust backend calculations, this tool represents a significant advancement in the methodology for planning and executing CH4 emission studies in dairy cows, aligning with global efforts toward sustainable agricultural practices and environmental conservation.

Effect of carbohydrate type in silages and concentrates on feed intake, enteric methane and milk yield from dairy cows

Dietary carbohydrate manipulation can be used to reduce enteric CH4 emission, but there is a lack of studies on the interaction of different types of carbohydrates that can affect feed intake and ruminal fermentation. Understanding this interaction is necessary to make the most out of CH4 mitigation feeding strategies using different dietary carbohydrates. The aim of this study was to test the effect on enteric CH4 emission, feed intake and milk production response when cows were fed either grass-clover (GCS) or corn silage (CS) as the sole forage source (55% of dry matter, DM), in combination with either barley (BAR) or dried beet pulp (DBP) as a concentrate (21.5% of DM). Twenty-four (half first and half second parity) cows were used in a crossover design with 2 periods of 21 d each, receiving 2 of 4 diets obtained from a 2 × 2 factorial arrangement of the experimental diet. Feed intake, CH4 emission metrics and milk production were recorded at the end of the experimental periods. The diets had NDF concentrations between 258 and 340 g/kg of DM, and starch concentrations between 340 and 7.45 g/kg of DM (CS-BAR and GCS-DBP, respectively). The effects of silage and concentrate on dry matter intake (DMI) were additive, with the highest feed intake in cows fed COR-BAR, followed by cows fed COR-DBP, GCS-BAR, and GCS-DBP (21.2, 19.9, 19.1, and 18.3 kg/d). Energy corrected milk (ECM) yield was not affected by silage source in first parity cows, but it was higher for cows fed CS than cows fed GCS in second parity. The effects of silage and concentrate on CH4 production (g/d), yield (g/kg of DMI) and intensity (g/kg of ECM) were not additive as cows fed GCS had similar responses regardless of the concentrate used, but cows fed CS had lower CH4 production, yield and intensity, when fed BAR instead of DBP. The lower CH4 production, yield and intensity in cows fed CS-BAR compared with other diets could be partially explained by the nonlinear relationship between ruminal VFA and carbohydrates (NDF and starch) concentration reported in literature, however, we observed a linear relationship between acetate:propionate ratio and CH4 yield, suggesting possible other effects. The effects of silage and concentrate on the ruminal VFA were additive in first parity cows, but not in second parity cows. The interaction between dietary CHO type and parity might indicate an effect of feed intake or the energy balance of the cow. Feeding cows silage and concentrate both rich in starch can result in the lowest enteric CH4 emission.

Acute dose-response effect of photobiomodulation therapy on 5-km running performance in trained runners: a randomized, double-blind, placebo-controlled, crossover study.

Photobiomodulation therapy (PBMT) has been advocated as a potential intervention to improve muscle performance and recovery in the health and sports context. However, the short- and long-term effects of PBMT on endurance running performance remain under-researched and controversial. The purpose of this study was to investigate the acute dose-response effect of PBMT with light-emitting diodes (LEDs) on endurance performance and rating of perceived exertion (RPE; 6-20 Borg) during a 5-km running trial in recreational runners. In a crossover design, eighteen young adult runners (28.7 ± 7.8 years) were randomized to receive 1 of 4 PBMT conditions (placebo, 300, 900, and 1260 Joules [J]) 60min before the 5-km running trial on four occasions, separated by a 2-wk washout period. The treatments were applied to the quadriceps, hamstrings, and gastrocnemius muscles of both legs using a device containing 200 LEDs (100 red and 100 infrared). The following variables were assessed: endurance performance (i.e. total time, mean velocity, and velocity in the split distances at the initial 200m and every 400m lap) and RPE in the split distances at the initial 200m and every 400m lap. Data normality and homogeneity were tested using Shapiro-Wilk's and Levene's tests, respectively. Differences between treatment conditions were assessed using the analysis of variance tests (one- or two-way ANOVA, depending on the comparisons), complemented by the Bonferroni post hoc test. There were significant time effects for the running velocity and RPE in the split distances (p < 0.0001), with no significant treatment-by-time interaction (running velocity, p = 0.59; RPE, p = 0.95). The mean velocity (p = 0.997), total time (p = 0.998), and total mean of the RPE (p = 0.91) were similar between treatment conditions. In conclusion, acute PBMT with LEDs at doses of 300, 900, and 1260J is not recommended for improving endurance performance and RPE in the 5-km running trial in recreational runners.

Beta2-agonist impairs muscle insulin sensitivity in persons with insulin resistance.

Given the promising effects of prolonged treatment with beta2-agonist on insulin sensitivity in animals and non-diabetic individuals, the beta2-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta2-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance. To assess the impact of beta2-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects. In a cross-over design, we assessed the effect of beta2-agonist on insulin-stimulated muscle glucose uptake during a 3-h hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant overweight subjects. Two hours into the clamp, we infused beta2-agonist. We collected muscle biopsies before, two hours into and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques. We establish that beta2-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta2-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. While both beta2-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta2-agonist attenuated incorporation of glucose into glycogen. Our findings suggest that beta2-agonist inhibits glycogenesis while intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta2-agonist.

Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen.

Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of adverse cardiovascular events via suppression of cyclooxygenase (COX)-2-derived prostacyclin (PGI2) formation in heart, vasculature, and kidney. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial and other large clinical studies compared the cardiovascular risk of traditional NSAIDs (i.e. naproxen), which inhibit both COX isozymes, with NSAIDs selective for COX-2 (i.e. celecoxib). However, whether pharmacologically equipotent doses were used - that is, whether a similar degree of COX-2 inhibition was achieved - was not considered. We compared drug target inhibition and blood pressure response to celecoxib at the dose used by most patients in PRECISION with the lowest recommended naproxen dose for osteoarthritis, which is lower than the dose used in PRECISION. Sixteen healthy participants (19-61 years) were treated with celecoxib (100 mg every 12h), naproxen (250 mg every 12h), or placebo administered twice daily for seven days in a double-blind, crossover design randomized by order. On Day 7 when drug levels had reached steady state, the degree of COX inhibition was assessed ex vivo and in vivo. Ambulatory blood pressure was measured throughout the final 12h dosing interval. Both NSAIDs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9±21.7%) than celecoxib (35.7±25.2%; p<0.05). Similarly, naproxen treatment inhibited PGI2 formation in vivo (48.0±24.9%) to a greater degree than celecoxib (26.7±24.6%; p<0.05). Naproxen significantly increased blood pressure compared to celecoxib (differences in least-square means of mean arterial pressure: 2.5 mm Hg (95% CI: 1.5, 3.5); systolic blood pressure: 4.0 mm Hg (95% CI: 2.9, 5.1); diastolic blood pressure: 1.8 mm Hg (95% CI: 0.8, 2.8); p<0.05 for all). The difference in systolic blood pressure relative to placebo was associated with the degree of COX-2 inhibition (p<0.05). Celecoxib 200 mg/day inhibited COX-2 activity to a lesser degree than naproxen 500 mg/day, resulting in a less pronounced blood pressure increase. While the PRECISION trial concluded the non-inferiority of celecoxib regarding cardiovascular risk, this is based on a comparison of doses that are not equipotent.ClinicalTrials.gov identifier: NCT02502006 (https://clinicaltrials.gov/study/NCT02502006).

The application of heating film to hands reduces the decline in manual dexterity performance associated with cold exposure.

Exposure to cold temperatures decreases finger temperature (Tfing) and dexterity. Decreased manual function and dexterity can be serious safety risks, especially in tasks that require fine motor movements that must be performed outdoors. The aim of this study was to determine whether hand heating with a minimal power requirement (14.8W) results in a smaller reduction in Tfing and manual dexterity performance during mild cold exposure compared to a non-heated control condition. In a randomized crossover design, twenty-two healthy participants were exposed to a moderately cold environment (5 ºC) for 90min. One condition had no intervention (CON), while the other had the palmar and dorsal hands heated (HEAT) by using electric heating films. Tfing and cutaneous vascular conductance (CVC) were continuously monitored using laser Doppler flowmetry. Manual dexterity performance and cognitive function were assessed by the Grooved Pegboard Test (GPT) and Stroop Color-Word (SCW) test, respectively, during the baseline period and every 30min during the cold exposure. After the cold exposure, Tfing was higher in HEAT relative to CON (CON 9.8 vs. HEAT 13.7ºC, p < 0.0001). GPT placing time, as an index of dexterity performance, was also shorter in HEAT by 14.5% (CON 69.10 ± 13.08 vs. HEAT 59.06 ± 7.99s, p < 0.0001). There was no difference in CVC between the two conditions during the cold exposure (p > 0.05 for all). Cognitive function was similar between two conditions (p > 0.05 for all). The proposed hand heating method offers a practical means of heating fingers to maintain dexterity throughout prolonged cold exposure.

Evaluation of a novel palm-free fat supplement to reduce the carbon footprint of diets for dairy cows

Most fat supplements added to dairy diets are derived from palm acid oil or palm fatty acid distillate. There are environmental concerns about palm oil production due to deforestation and high greenhouse gas (GHG) emissions. The objective of this study was to evaluate a palm-free fat supplement, Envirolac. Envirolac contains vegetable oils, marine oils and glycerine encapsulated within a cellulosic fibre-clay mineral carrier matrix. The carrier matrix has small particle size to facilitate rapid rumen passage and minimal interference with rumen digestion. Fifty cows were divided into two balanced groups of 25 cows. Each group received Control (calcium soap of palm fatty acid distilate, 0.5 kg/d) and Envirolac (0.5 kg/d) diets in a crossover design with two feeding periods of four weeks duration, so that each cow received both diets. Envirolac has a lower total fat concentration than the calcium soap, so the feeding rate delivered less total fat. When fed on Envirolac, cows yielded more milk 40.7 v 40.1 kg/d), energy-corrected milk (ECM; 42.9 v 41.3 kg/d) and milk components (1605 v 1514 g fat, 1239 v 1199 g protein, 1871 v 1839 g lactose, per day), and produced milk with higher concentrations of fat (40.1 v 38.6 g/kg) and protein (30.7 v 30.1 g/kg), than when fed on Control. When fed on Envirolac, cows produced milk with higher concentrations of fatty acids (FA) synthesised de novo in the mammary gland (25.5 v 23.6 g/100 g total FA), lower concentration of palmitic acid (35.5 v 37.2 g/100 g total FA), and higher concentrations of some long-chain fatty acids (C20:0, C20:1, C20:3n3, C21:0, C22:0, C22:6n3 and C23:0), than when fed on Control. There was no effect of treatment on dry matter intake (DMI; mean 23.4 kg/d), so feed efficiency was higher (1.83 v 1.76 kg ECM/kg DMI) for Envirolac than Control. There was no effect of treatment on dry matter digestibility (0.73), methane production (433 g/d), methane yield (19.3 g/kg DMI) or methane intensity (10.9 g/kg ECM). Feed carbon footprint of Envirolac was calculated to be 1028 g CO2eq/kg DM, which is 0.46 of the value for a calcium soap (2830 g CO2eq/kg DM), and reduced feed carbon footprint per kg ECM milk production by 11 %. This study demonstrates that Envirolac can replace palm-based fat supplements in dairy diets to improve feed efficiency and reduce the carbon footprint of milk production.

The Effects of Post-Exercise Cold Water Immersion on Neuromuscular Control of Knee.

To date, most studies examined the effects of cold water immersion (CWI) on neuromuscular control following exercise solely on measuring proprioception, no study explores changes in the brain and muscles. The aim of this study was to investigate the effects of CWI following exercise on knee neuromuscular control capacity, and physiological and perceptual responses. In a crossover control design, fifteen participants performed an exhaustion exercise. Subsequently, they underwent a 10 min recovery intervention, either in the form of passively seated rest (CON) or CWI at 15 °C. The knee proprioception, oxygenated cerebral hemoglobin concentrations (Δ[HbO]), and muscle activation during the proprioception test, physiological and perceptual responses were measured. CWI did not have a significant effect on proprioception at the post-intervention but attenuated the reductions in Δ[HbO] in the primary sensory cortex and posterior parietal cortex (p < 0.05). The root mean square of vastus medialis was higher in the CWI compared to the CON. CWI effectively reduced core temperature and mean skin temperature and improved the rating of perceived exertion and thermal sensation. These results indicated that 10 min of CWI at 15 °C post-exercise had no negative effect on the neuromuscular control of the knee joint but could improve subjective perception and decrease body temperature.

Influence of nitrate supplementation on motor unit activity during recovery following a sustained ischemic contraction in recreationally active young males.

Dietary nitrate (NO3-) supplementation enhances muscle blood flow and metabolic efficiency in hypoxia, however, its efficacy on neuromuscular function and specifically, the effect on motor unit (MU) activity is less clear. We investigated whether NO3- supplementation affected MU activity following a 3min sustained ischemic contraction and whether this is influenced by blood flow restriction (BFR) during the recovery period. In a randomized, double-blinded, cross-over design, 14 males (mean ± SD, 25 ± 6years) completed two trials following 5days of supplementation with NO3--rich (NIT) or NO3--depleted (PLA) beetroot juice to modify plasma nitrite (NO2-) concentration (482 ± 92 vs. 198 ± 48nmol·L-1, p < 0.001). Intramuscular electromyography was used to assess MU potential (MUP) size (duration and area) and mean firing rates (MUFR) during a 3min submaximal (25% MVC) isometric contraction with BFR. These variables were also assessed during a 90s recovery period with the first half completed with, and the second half completed without, BFR. The change in MUP area and MUFR, did not differ between conditions (all p > 0.05), but NIT elicited a reduction in MUP recovery time during brief isometric contractions (p < 0.001), and during recoveries with (p = 0.002) and without (p = 0.012) BFR. These novel observations improve understanding of the effects of NO3- on the recovery of neuromuscular function post-exercise and might have implications for recovery of muscle contractile function. The study was registered on clinicaltrials.gov with ID of NCT05993715 on August 08, 2023.