Crossover Design Research Articles

Evaluation of a continuous glucose monitoring system in healthy dairy calves and adult goats.

To determine the accuracy of a continuous glucose monitoring system (CGMS) device by comparing glucose concentrations measured over time as determined by the CGMS to those of the chemistry analyzer (reference method). 7 healthy goats and 7 dairy calves. A randomized, crossover design with 3 treatments: control, hypoglycemia, and hyperglycemia. The CGMS device was applied to the neck. Hypoglycemia and hyperglycemia were induced by insulin and xylazine, respectively. Glucose concentrations were measured by the chemistry analyzer CGMS, point-of-care glucometer, and intensive care unit machine at 0 (before treatment), 2, 4, 6, 8, 10, and 12 hours. Agreement between the CGMS and the chemistry analyzer was determined by Bland-Altman plots. The analytical and clinical accuracy of the CGMS was determined using the International Organization for Standardization (ISO) 15197:2013 criteria and the Parkes error grid analysis. In goats, the CGMS overestimated glucose concentrations during the hypoglycemic, normoglycemia, and hyperglycemia treatments. In calves, the CGMS underestimated glucose concentrations during the hypoglycemic treatment but overestimated glucose concentrations in normoglycemia and hyperglycemic treatments. The CGMS met the ISO clinical accuracy criteria for goats and calves, with > 99% of the glucose measurements in zones A and B of the Parkes grid. However, the CGMS did not meet the ISO 15197:2013 criteria for analytical accuracy. The CGMS evaluated in our study only met the ISO 15197:2013 clinical accuracy criteria, not the analytical accuracy. Therefore, the device might be considered for clinical use.

Phenotypic traits related to methane emissions from Holstein dairy cows challenged by low or high forage proportion

Limited literature is available identifying phenotypical traits related to enteric methane (CH4) production from dairy cows, despite its relevance in relation to breeding for animals with a low CH4 yield (g/kg DMI), and the derived consequences hereof. This study aimed to investigate the relationships between CH4 yield and different animal phenotypes when 16 2nd parity dairy cows, fitted with a ruminal cannula, were fed 2 diets differing in forage:concentrate ratio in a crossover design. The diets had either a low forage proportion (35% on DM basis, F35) or a high forage proportion (63% on DM basis, F63). Gas exchange was measured by means of indirect calorimetry. Spot samples of feces were collected, and indigestible NDF (INDF) was used as an internal marker to determine total-tract digestibility. In addition, ruminal evacuations, monitoring of chewing activity, determination of ruminal VFA concentration, analysis of relative abundance of methanogens, and measurement of liquid passage rate were performed. Statistical differences were analyzed by a linear mixed model with diet, days in milk, and period as fixed effects, and cow as random effect. The random cow estimates (RCE) were extracted from the model to get the Pearson correlations (r) between RCE of CH4 yield with RCE of all other variables measured, to identify possible phenotypes related to CH4 yield. Significant correlations were observed between RCE of CH4 yield and RCE of OM digestibility (r = 0.63) and ruminal concentration of valeric acid (r = -0.61), acetic acid (r = 0.54), ammonium (r = 0.55), and lactic acid (r = ‒0.53). Additionally, tendencies were observed for correlations between RCE of CH4 yield and RCE of H2 yield in g/kg DM (r = 0.47, P = 0.07), and ruminal isobutyric acid concentration (r = 0.43, P = 0.09). No correlations were observed between RCE of CH4 yield and RCE of ruminal pool sizes, milk data, urinary measurements, or chewing activity. Cows had a lower DMI and ECM, when they were fed F63 compared with F35. Cows fed F63 had higher NDF digestibility, CH4 emissions (g/d, g/kg of DMI, and g/kg of ECM), ruminal concentration of acetic acid, ruminal pH, degradation rate of digestible NDF (DNDF, %/h), and longer rumen retention time (h). Also, rumination and total chewing time (min/kg DMI) were higher for cows fed F63. The results in the present study emphasize the positive relation between cow's ability to digest OM and their CH4 emissions. The derived consequences of breeding for lower CH4 emission might be cows with lower ability to digest OM, but more studies are warranted for further documentation of this relationship.

The effects of facial cooling on physiological and perceptual responses during a simulated Épée fencing competition: a pilot study.

The aim of this study was to investigate the effects of facial cooling on physiological and perceptual responses during a simulated fencing competition. Using a randomized, crossover design, six competitive male fencers completed two trials of seven simulated fencing matches. Each match consisted of 22×10 s bouts of high-intensity fencing movements. Static rest (12 s) separated each bout, with 60-second rest after bouts seven and 14, during which, in the experimental condition, participants were sprayed with a facial water mist and fanned. Relative to control, facial cooling reduced tympanic temperature (mean difference [MD]: 0.2±0.03 °C; 95% likely range [CL<inf>95</inf>]: 0.13-0.3 °C), heart rate (MD: 12±3 b·min-1; CL<inf>95</inf>: 5-20 b·min-1), and ratings of perceived exertion (RPE) for the dominant arm (MD: 2±0; CL<inf>95</inf>: 1-3), legs (MD: 2±0; CL<inf>95</inf>: 1-3), and total exertion (MD: 2±0; CL<inf>95</inf>: 1-3). Moreover, the benefits of facial cooling on RPE of the dominant arm and legs were magnified as the competition progressed. Facial cooling also improved ratings of perceived thermal comfort and perceived thermal strain. While the performance benefits of the intervention require exploration, facial misting positively affects both physiological and perceptual responses during fencing.

The effects of acute aerobic exercise on appetite-regulating parameters and energy intake in males with obesity.

To investigate the effects of moderate-intensity aerobic exercise on appetite control parameters, appetite perceptions, and energy intake in sedentary males with obesity. Eleven males with obesity (body fat percentage 36.5 ± 2.5%, body mass index 35.3 ± 4.2 kg/m2, V̇O2peak 29 ± 3.1 mL·kg-1·min-1) completed two experimental sessions: (1) no exercise (CTRL) and (2) 60 min of moderate-intensity cycling exercise at 60% V̇O2peak (MICT) in a crossover design. Blood analysis included growth differentiation factor 15 (GDF-15), total ghrelin, peptide tyrosine tyrosine3-36 (PYY3-36), total glucagon-like peptide-1 (GLP-1), insulin, and glucose, as well as subjective appetite perceptions were measured in specific intervals. A standard breakfast at 0 h and an ad libitum meal postexercise was provided. GDF-15 (95% confidence interval [CI]: [2.48-27.28] ng/L, p = 0.021) increased immediately following MICT compared to CTRL. However, there were no differences for PYY3-36 (p = 0.480, ), total ghrelin (p = 0.646, ), and total GLP-1 (p = 0.451, ) between sessions. Appetite perceptions (95% CI: [(-20.38)-(-6.16)] mm, p = 0.001) were suppressed following MICT though energy intake was not different between the sessions (95% CI: [(-1904.9)-928.1] kJ, p = 0.480). Sixty minutes of MICT increased GDF-15 while suppressing appetite perceptions in individuals with obesity. There was no energy compensation postexercise.

The Effect of Meal Frequency and Glycemic Index During the Night Shift on Alertness, Hunger, and Gastrointestinal Complaints in Female Health Care Workers—A Two-Armed Randomized Crossover Trial

BackgroundNutrition strategies for night-shift workers could optimize alertness and minimize hunger and reduce gastrointestinal complaints, enhancing safety and well-being. ObjectivesThis study aimed to investigate the effects of 1 or 3 small meals, with either low or high glycemic index (GI), compared with no meal, on alertness, hunger, and gastrointestinal complaints during the night shift. MethodsFifty-one female health care workers, aged 18 to 61 Y, participated in a 2-armed randomized crossover design. In 1 study arm, participants received 1 yogurt meal during the night shift, AND in the other, they received 3. Each study arm involved 3 intervention periods during night shifts, with participants consuming yogurt with low GI (1LGI or 3LGI) OR high GI (1HGI or 3HGI) carbohydrates, or no meal (0NGI). Objective alertness was assessed using a validated brief psychomotor vigilance task (PVT-B), subjective alertness with the Samn–Perelli scale, and hunger and gastrointestinal complaints through questionnaires. ResultsParticipants in the 1LGI (β: −4.6; 95% CI: 0.0, 9.3) and 3LGI (β: −3.4; 95% CI: 0.0, 6.8) conditions had fewer lapses during the PVT-B than those in the 3HGI condition. No differences were found between meal conditions for median and reciprocal reaction time or subjective alertness. All 4 conditions reported less hunger (β: from −0.6 to −1.2) compared with no meal. The 3LGI condition resulted in more rumbling intestines than the 3HGI (β: 1.1; 95% CI: 0.4, 1.7) and 0NGI (β: 0.74; 95% CI: 0.11, 1.37) conditions. ConclusionsOur study suggests that consuming 3 small low GI meals during the night shift helps maintain alertness and reduces lapses compared with 3 high GI meals. It also minimizes hunger but may cause mild gastrointestinal complaints.This trial was registered at International Clinical Trial Registry (https://trialsearch.who.int/Trial2.aspx?TrialID%3dNL-OMON25574).

The Effects of Foam Rolling at Different Speeds on Mechanical Properties of Quadriceps Femoris.

Foam rolling have gained popularity among elite athletes, but the effect of the speed parameter of foam rolling has not yet been determined. Our objective was to investigate the impact of different application speeds of foam roller on the mechanical properties of the quadriceps femoris muscle. Eighteen male professional basketball athletes (age 23 ± 4 years, body mass index 24.43 ± 1.59 kg/m2) participated in this study. We used a crossover design to randomize the order of the treatment speeds (30 beats per minute-FAST, 15 beats per minute-SLOW, and a self-determined speed-SELF) with a one-week washout period between each session. We measured dominant quadriceps femoris muscle tone, elasticity, and stiffness using the Myoton device before and after the interventions. We found that the average rate for SELF was 33±10 beats per minute, making SELF the fastest. All application speeds showed similar results in pre-intervention measurements of the mechanical properties of the tissues (P > 0.05). However, post hoc analysis revealed that a decrease was evident in SLOW compared to SELF in muscle tone in post-intervention measurements (P = 0.037). Also, we noted that comparison of pre- and post-intervention on FAST and SLOW showed a significant reduction in muscle tone (P = 0.002, P = 0.008). Slower foam rolling prior to training or competition may lead to a delay in the reaction time due to the reduction in tonus, that can increase the injury risks. Alternatively, the significant reduction in tonus may be useful in regulating the increased tonus after training and competition.

Valenced dual tasking in patients with posttraumatic stress disorder.

Dual-tasking studies show that emotionality and vividness of aversive memory decrease by engaging in a working memory task and simultaneous recall of that memory. Adding positive valence to a dual task might be a promising innovation in the amelioration of lab-induced memory. However, studies aiming to translate these findings into autobiographical memory of a posttraumatic stress disorder (PTSD) population find conflicting results or show methodological flaws. The current study assesses the benefit of adding positive valence to a dual-tasking procedure in PTSD patients. In a cross-over design PTSD patients (N = 33) recalled their traumatic memory and received the following three conditions in randomized order: rating positive pictures + exposure, rating neutral pictures + exposure, and exposure only. Each of the three conditions consisted of four sets of 1 min. In the first cycle, participants were exposed to each condition in a randomized order, which was then repeated in a second cycle. Before and after each condition, emotionality and vividness were rated on a visual analog scale (VAS), resulting in seven measurement timepoints in total. Firstly, repeated measures ANOVAs showed a time effect: memories were less emotional and vivid after our summed (three) interventions. Secondly, repeated measures ANCOVAs indicated no evidence for differences between the conditions. We did not find evidence for a benefit of adding positive valence to a dual-task procedure in PTSD patients. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pharmacokinetic Pattern of Menbutone in Calves after Single Intravenous and Intramuscular Administration.

Menbutone is a choleretic agent currently used in Europe to treat digestive disorders in livestock and dogs. Pharmacokinetic parameters were established in 4-month Holstein calves after intravenous (IV) and intramuscular (IM) administration. The drug was administered to 12 animals (10 mg/kg) for both IV and IM routes following a crossover design. Plasma samples were collected at various time points over 24 h and analyzed by reverse-phase high-performance liquid chromatography with a photodiode-array detector, following a method validated according to European Medicines Agency guidelines. Pharmacokinetic parameters were calculated using compartmental and non-compartmental methods. Menbutone followed a two-compartment open model after IV injection, with a total clearance (Cl) of 71.9 ± 13.5 mL/h/kg, an elimination half-life (t½β) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (Vss) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t½λ) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (Cmax) was 15.1 ± 4.3 µg/mL; the time to reach Cmax (tmax), 1.66 ± 0.55 h; and the mean absorption time (MAT), 2.50 ± 1.42 h. Absorption was high, with a fraction of the dose absorbed (F) of 83.5 ± 22.4%. Menbutone was rapidly eliminated from plasma for both routes of administration, with a fast and high IM bioavailability.

Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Acute effects of exercise on gaze fixation and affective response inhibition in children with autism spectrum disorder: A randomized cross-over study.

Children with autism spectrum disorder (ASD) show impairments in response inhibition, especially in socio-emotional contexts. A single aerobic exercise session has the potential to temporarily reduce such impairments as findings from neurotypical children support acute benefits of this exercise type for inhibitory control and emotion recognition. In children with ASD, we therefore aimed to investigate the effects of an aerobic exercise bout on response inhibition in an emotional Go/NoGo task and gaze fixation as possible mechanism underlying changes in performance. Using a cross-over design, 29 patients completed a 20-min aerobic exercise bout at moderate intensity on a cycling ergometer and a control condition in a randomized order. An emotional Go/NoGo task was administered before and after both experimental conditions. Eye-tracking was performed during the cognitive task to assess the duration of gaze fixation of eyes and mouth parts of faces expressing happy or sad emotions. The results support no beneficial effect of exercise on performance on the emotional Go/NoGo task. Instead, patients showed a greater decrease in accuracy on Go trials displaying happy faces in the exercise compared to the control condition. This change was associated with a more pronounced decrease in the fixation duration of the eyes for faces expressing either happy or sad emotions. In conclusion, while a single session of moderately intense aerobic exercise does not affect response inhibition, it temporarily aggravates ASD-specific deficits in the processing of and response to facial emotions.

Time to resolution of airway inflammation caused by bronchoalveolar lavage in healthy horses.

Bronchoalveolar lavage (BAL) is a common procedure for evaluation of the equine lower airways. Time to resolution of post-BAL inflammation has not been clearly defined. Residual inflammation, evident by changes in immune cell populations and inflammatory cytokines, will resolve by 72 hours after BAL. Six adult, healthy, institution-owned horses. Randomized, complete cross-over design. Each horse underwent 3 paired BALs, including a baseline and then 48, 72, and 96 hours later, with a 7-day washout between paired BALs. Each sample underwent cytological evaluation and cytokine concentrations were determined by a commercially available multiplex bead immunoassay. Statistical analysis was performed by multilevel mixed-effects Poisson regression analysis. Data are reported as marginal means and 95% confidence interval (CI). Neutrophil, eosinophil and mast cell percentages were not significantly different at any time points. Macrophage percentages were higher at 72 hours (45.0 [95% CI, 41.6-48.4]%) and 96 hours (45.3 [95% CI, 42.9-47.7]%) vs baseline (37.4 [95% CI, 33.5-41.4]%; P < .001 and P = .01, respectively), and at 72 hours and 96 hours vs 48 hours (31.9 [95% CI, 28.1-35.6]%; P < .001). Neutrophil percentage was not significantly increased at 48 hours (P = .11). Interleukin (IL)-6 concentration was increased at 72 hours (5.22 [95% CI, 3.44-6.99] pg/mL) vs 48 hours (4.38 [95% CI, 2.99-5.78] pg/mL; P < .001). Significant lung inflammation was not detected at 72 and 96 hours, suggesting that repeating BAL at 72 hours or more can be done without concern of residual inflammation.

Exercise induced hypoalgesia after a high intensity functional training: a randomized controlled crossover study

BackgroundAcute physical activity often induces an acute reduction in pain sensitivity known as exercise induced hypoalgesia (EIH). The aim of this study was to investigate the effects of a high intensity functional training (HIFT) on EIH compared to a control session.Methods50 (age: 26.0 ± 2.7; 23 female) participants successfully conducted this study consisting of a pre-experimental test as well as a 12-minute HIFT (body-weight exercises) and a 12-minute control (supervised breathing) session in a randomized crossover design. Pre and post, pressure pain thresholds (PPT) were measured at the ankles, knees, elbows, and forehead.ResultsThe HIFT resulted in a relative maximum and average heart rate of 96.2% (± 3.6%) and 91.1% (± 4.2%), respectively, and maximum and average RPE values of 19.1 (± 1.2) and 16.2 (± 1.4), respectively. Results reveal a significant ‘Intervention’ × ‘Time point’ interaction (p < 0.001) for PPT (pooled for one average value) with hypoalgesia observed following the HIFT (p < 0.001; pre: 56.0 ± 16.8, post: 61.6 ± 19.0 [Newton]) and no change following the control (p = 0.067; pre: 56.6 ± 18.4, post: 55.3 ± 18.9 [Newton]). Further, a significant ‘Time’ × ‘Intervention’ × ‘Landmark’ interaction effect (p = 0.024) is observed and all landmarks showed significant hypoalgesia following HIFT (p < 0.01), except for the right elbow and forehead. Following control, no hypoalgesia was observed at any landmark. Analysing male and female participants separately, it was observed that EIH occured only in men.ConclusionA HIFT using bodyweight exercises reduces pain sensitivity. Hence, combining strength and aerobically demanding exercises in a short but high intensity manner, as done in HIFT, can be seen as a usable tool to induce hypoalgesia. Yet, these results were observed only in male participants, necessitating future sex-specific research.Trial registrationDRKS00034391, retrospectively registered on the 4th of June 2024.

Pharmacokinetic Evaluation of Amlodipine Tablet Compared with Norvask® Tablet in Healthy Indonesian Adults

This study objective to evaluate the pharmacokinetics of Amlodipine 10 mg Produced by PT. Tropica Mas Pharmaceuticals compared to Norvask® 10 mg Tablet Produced by PT. Pfizer Indonesia, in healthy Indonesian Adults through bioequivalence study. This study is utilized by randomized, single-dose, openlabel, two-way cross-over design with a washout period 14 days and fasting. This study involved 18 subjects, with only 17 subjects included in the statistical analysis, because 1 subject withdrew due to diarrhoea in the 2nd period. Plasma samples were collected 17 times for 72-hour per period. Amlodipine concentrations were measured using LCMS/MS. Bioequivalence was determined by value of 90% confidence interval (CI) with α = 5.00% within the range of 80.00–125.00% for AUC and Cmax. The geometric mean ratios (90% CI) of the test drug vs. the innovator drug were 101.67% (97.16 – 106.39) for AUC0-t and 100.46% (95.00 – 106.23) for Cmax. Based on the result, the test drug is bioequivalent to the comparator drug.

High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist. The aims of this study were (1) to demonstrate the feasibility of treating aggression with high-dose propranolol using telehealth study visits and (2) to document cardiac safety. This study utilized a randomized, double-blind, placebo-controlled, crossover design. Dosing was titrated up in a flexible but stepwise fashion until therapeutic response was obtained or up to 200 mg tid. Following washout, those who were assigned propranolol were crossed over to placebo and vice versa. Six participants between the ages 12-19 participated. The primary outcome measures were the final Clinical Global Impression Improvement Scale (CGI-I) and the Aberrant Behavior Checklist-Community Irritability (ABC-C/I) scores at 200 mg tid. The CGI-I indicated a 50% reduction in symptoms in the propranolol phase, while the ABC-I indicated a 37% reduction in comparison to placebo. The effect sizes ( r ) for the CGI-I and the ABC-C/I were large, -0.74 and -0.64, respectively. The average blood pressure was 122/68 during the placebo phase and 109/72 during the propranolol phase. All Holter monitor exams were unremarkable. These results suggest that propranolol is an effective option in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed.

Teaching medical students hematopathology: a randomized crossover study comparing direct inspection by light microscope versus projected images.

Students' ability to diagnose various blood disorders could be substantially improved by continuously reviewing approaches toward teaching hematology. This study aims to compare the effectiveness of light microscopes and projected images on students' learning and determine medical students' perception of these teaching methods. A randomized trial was conducted using a crossover design. Two groups, each with 30 students, were subjected to teaching methods based on light microscopes and projected images alternatively. No differences were found in the two study groups' baseline characteristics, such as median age, sex, and prior academic performance, as well as in the pre-test scores. Post-test scores were significantly higher among students subjected to the projection method than in the control group (Mean ± SD = 9.8 ± 1.7 vs. 5.1 ± 1.3, p < 0.001). In the post-cross-over assessment, 85% (n = 51) of students reported their satisfaction for the projected images, and 78% (n = 47) of students were willing to be taught by projection. Students perceived that the projection method facilitated participation and better involvement in discussions, improved learning, provided greater motivation, and eventually increased comprehension and efficiency. The projection-based teaching method is more effective in improving knowledge and achieving intended learning outcomes. Students tend to prefer the projection method over the laboratory-based method and perceive it as an effective method to enhance their learning of hematology.

Ketone monoester attenuates declines in cognitive performance and oxygen saturation during acute severe hypoxic exposure under resting conditions.

Exogenous ketone supplements are a potential augmentation strategy for cognitive resilience during acute hypoxic exposure due to their capacity to attenuate the decline in oxygen (O2) availability, and by providing an alternative substrate for cerebral metabolism. Utilizing a single-blind randomized crossover design, 16 male military personnel (age, 25.3±2.4year, body mass, 86.2±9.3kg) performed tests of cognitive performance at rest in three environments: room air (baseline), normoxia (20min; 0m; 20.9% O2) and hypoxia (20min; 6096m, 9.7% O2) using a reduced O2 breathing device (ROBD). (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME; 650mg/kg, split dose given at 30min prior to each exposure) or taste-matched placebo (PLA) was ingested prior to normoxia and hypoxic exposure. Blood R-βHB and glucose concentrations, cognitive performance and O2 saturation ( ) were collected throughout. KME ingestion increased blood R-βHB concentration, which was rapid and sustained (>4mM 30min post; P<0.001) and accompanied by lower blood glucose concentration (∼20mg/dL; P<0.01) compared to PLA. Declines in cognitive performance during hypoxic exposure, assessed as cognitive efficiency during a Defense Automated Neurobehavioral Assessment (DANA) code substitution task, were attenuated with KME leading to 6.8 (95% CL: 1.0, 12.6) more correct responses per minute compared to PLA (P=0.018). The decline in during hypoxic exposure was attenuated (6.40% ; 95% CL: 0.04, 12.75; P=0.049) in KME compared to PLA (KME, 76.8±6.4% ; PLA, 70.4±7.4% ). Acute ingestion of KME attenuated the decline in cognitive performance during acute severe hypoxic exposure, which coincided with attenuation of declines in O2 saturation.

Ketone monoester attenuates oxygen desaturation during weighted ruck exercise under acute hypoxic exposure but does not impact cognitive performance.

Acute ingestion of exogenous ketone supplements in the form of a (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME) can attenuate declines in oxygen availability during hypoxic exposure and might impact cognitive performance at rest and in response to moderate-intensity exercise. In a single-blind randomized crossover design, 16 males performed assessments of cognitive performance before and during hypoxic exposure with moderate exercise [2×20min weighted ruck (∼22kg) at 3.2km/h at 10% incline] in a normobaric altitude chamber (4572m, 11.8% O2). The R-BD R-βHB KME (573mg/kg) or a calorie- and taste-matched placebo (∼50g maltodextrin) were co-ingested with 40g of dextrose before exposure to hypoxia. The R-βHB concentrations were rapidly elevated and sustained (>3mM; P<0.001) by KME. The decline in oxygen saturation during hypoxic exposure was attenuated in KME conditions by 2.4%-4.2% (P<0.05) compared with placebo. Outcomes of cognitive performance tasks, in the form of the Defense Automated Neurobehavioral Assessment (DANA) code substitution task, the Stroop color and word task, and a shooting simulation, did not differ between trials before and during hypoxic exposure. These data suggest that the acute exogenous ketosis induced by KME ingestion can attenuate declining blood oxygen saturation during acute hypoxic exposure both at rest and during moderate-intensity exercise, but this did not translate into differences in cognitive performance before or after exercise in the conditions investigated.

Potatoes Compared with Rice in Meals with either Animal or Plant Protein Reduce Postprandial Glycemia and Increase Satiety in Healthy Adults: A Randomized Crossover Study

BackgroundRice and pasta are recommended as healthier than potatoes on the basis of their glycemic index when eaten alone. ObjectivesThe study objective was to evaluate postprandial glycemia (PPG), appetite, and food intake (FI) at meals with potatoes or rice when consumed with either meatballs or their vegetarian substitute. MethodsIn a randomized, single-blinded, crossover design, 26 (13 males and 13 females) healthy adults (age: 18–45 y; body mass index [kg/m2]: 18.5–29.9) consumed isocaloric fixed amounts of either meatballs or vegetarian-substitute balls with ad libitum access to either baked French fries (BFF), instant mashed potatoes (IMPs), or rice (control). FI was measured at the meal and at an ad libitum pizza meal served 120 min later. Blood glucose (BG), appetite, and plasma insulin responses were measured within the meal (0–30 min), postmeal (30–120 min), within pizza meal (120–140 min), and post-pizza (140–170 min). Effects of protein source, carbohydrate (CHO) source, and sex and their interactions were analyzed using analysis of variance followed by Tukey’s post hoc test. ResultsParticipants consumed 23–25% less treatment meal energy (kcal), 32–34% less CHO energy (kcal), and 13–16% less total energy (kcal) after the BFF and IMP than rice meals (P < 0.0001). Postmeal BG was lower after IMP (6.76 ± 0.15; P < 0.0001) and rice (6.92 ± 0.15; P = 0.0012) compared with BFF (7.19 ± 0.15). Post-pizza BG was higher after rice (6.77 ± 0.09) than that after BFF (6.51 ± 0.09; P = 0.0012) and IMP (6.39 ± 0.09; P < 0.0001). Postmeal meaned insulin was higher after BFF (82.16 ± 8.58) and IMP (77.75 ± 8.60) compared with rice (56.44 ± 8.59; P < 0.002). Insulin during pizza meal was lower after BFF (17.14 ± 6.90) compared with both IMP (39.03 ± 6.90; P = 0.0060) and rice (34.21 ± 6.90; P = 0.0336). Meatballs led to lower BG (6.48 ± 0.09; P = 0.0076) and higher insulin (84.54 ± 5.87; P = 0.0406) post-pizza compared with their plant protein substitute (6.64 ± 0.09 and 73.18 ± 5.87, respectively). ConclusionsAdults consuming meatballs or plant-based substitute with ad libitum IMP had lower PPG post-treatment and at a later pizza meal compared with rice. Both IMP and BFF resulted in lower energy intake than after rice.This trial was registered at http://clinicaltrials.gov (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CKIJ&selectaction=Edit&uid=U0000IA4&ts=2&cx=-uf51kf) as NCT05610124. Protocol ID: 43406 (Postprandial Glycemia and Satiety of Meals with Potatoes, with and without Protein).

Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants.

Racemic 3,4-methylenedioxymethamphetamine (MDMA) acutely increases mood, feelings of empathy, trust, and closeness to others and is investigated to assist psychotherapy. Preclinical research indicates that S-MDMA releases monoamines and oxytocin more potently than R-MDMA, whereas R-MDMA more potently stimulates serotonin 5-hydroxytryptamine-2A receptors. S-MDMA may have more stimulant properties, and R-MDMA may be more psychedelic-like. However, acute effects of S- and R-MDMA have not been examined in a controlled human study. We used a double-blind, randomized, placebo-controlled, crossover design to compare acute effects of MDMA (125 mg), S-MDMA (125 mg), R-MDMA (125 mg and 250 mg), and placebo in 24 healthy participants. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics, and plasma oxytocin, prolactin, and cortisol concentrations. S-MDMA (125 mg) induced greater subjective effects ("stimulation," "drug high," "happy," "open") and higher increases in blood pressure than R-MDMA (both 125 and 250 mg) and MDMA (125 mg). Unexpectedly, R-MDMA did not produce more psychedelic-like effects than S-MDMA. S-MDMA increased plasma prolactin more than MDMA, and S-MDMA increased plasma cortisol and oxytocin more than MDMA and R-MDMA. The plasma elimination half-life of S-MDMA was 4.1 h after administration. The half-life of R-MDMA was 12 and 14 h after the administration of 125 and 250 mg, respectively. Half-lives for S-MDMA and R-MDMA were 5.1 h and 11 h, respectively, after racemic MDMA administration. Concentrations of the CYP2D6-formed MDMA-metabolite 4-hydroxy-3-methoxymethamphetamine were lower after R-MDMA administration compared with S-MDMA administration. The pharmacokinetic findings are consistent with the R-MDMA-mediated inhibition of CYP2D6. Stronger stimulant-like effects of S-MDMA in the present study may reflect the higher potency of S-MDMA rather than qualitative differences between S-MDMA and R-MDMA. Equivalent acute effects of S-MDMA, MDMA, and R-MDMA can be expected at doses of 100, 125, and 300 mg, respectively, and need to be investigated.Trial registration: ClinicalTrials.gov identifier: NCT05277636.

Impact of Interactions with a Puppy and Handler Versus a Handler Alone on Stress and Vitality in a University Setting: A Crossover Study.

Brief interactions with a well-behaved dog can enhance wellbeing, but most campus-based dog visitation programs employ adult, trained dogs. There is little research about the impact of puppies on wellbeing or stress in this context. The aim of this study was to examine changes in perceived stress and vitality after interacting with a puppy. Staff and students (N = 32) at an Australian university attended the campus on two occasions, one week apart, as part of a crossover design. Participants were pseudo-randomly allocated to a group whereby they spent 20 min interacting with a handler alone at Visit 1 and interacted with a puppy and handler at Visit 2, or another group which reversed the interaction order. Perceived stress and subjective vitality were measured before and after each interaction. The increase in vitality was greater in the group experiencing the puppy and handler interaction first (significant main effect, F(1,49) = 646.89, p = 0.024, η2p = 1.00), regardless of the visit, possibly due to a social lubricating effect by the puppy, which carried over to the 'handler alone' second visit. Reductions in perceived stress were greater after the interaction with the puppy, for both groups (significant interaction effect, F(1,49) = 5.13, p = 0.029, η2p = 0.11), indicating that the puppy's presence can reduce stress more than the handler alone. This extends the evidence for university-based dog-facilitated wellbeing programs, by showing that interactions with puppies can also be effective. This is important as it may mean that puppies already on campus as part of a socialization/training program can be incorporated into wellbeing programs for staff and students.