Crossover Design Research Articles

The effect of ischemic preconditioning on repeated sprint cycling performance: a randomized crossover study.

Ischemic preconditioning (IPC) has been suggested to improve exercise performance by 1-8%. Prior research concerning its impact on short-duration exercises, such as sprints, has been limited and yielded conflicting results. The aim of this study, which included a non-occlusion-based placebo control, was to determine whether IPC improves repeated sprint performance in a manner that accounted for psychophysiological effects. Twenty-two healthy males participated in this study, which employed a randomized crossover design. Following the 10-min baseline period, participants received intervention under four different conditions: 1) no-intervention control (CON); 2) non-occlusion-based placebo control (SHAM); 3) remote IPC (RIPC); and 4) local IPC (LIPC). Participants then performed a standardized repeated sprint cycling (5×10s maximal cycling sprint, separated by a 40-s rest in each set). Repeated sprint performance, as indexed by average power output, peak power output, and total work, the improvement was observed in the RIPC and LIPC during the initial phase (set 1-3) when compared with CON (P<0.05). SHAM condition also showed an increase in peak power output in the set 1 (CON 9.97±1.05 vs. SHAM 10.30±1.13 w/kg, P<0.05), which may represent a psychophysiological component in the IPC-induced improvement. Higher lactate concertation was found in the SHAM and LIPC groups, than in the CON group, 5 minutes after the exercise (CON 15.72±0.68 vs. SHAM 16.82±0.41 vs. LIPC 17.19±0.39 mmol/L, P<0.0001 for both, respectively). In conclusion, LIPC enhanced repeated sprint cycling performance during the initial phase, beyond what could be accounted for entirely by a psychophysiological effect. The improvement associated with RIPC, however, did not surpass the effect of a placebo intervention.

Acute Effects of Cadence-Controlled Walking on Cognition and Vascular Function in Physically Inactive Older Adults: A Randomized Crossover Study.

Cadence-controlled walking may be a desirable approach for older adults to self-monitor exercise intensity and achieve physical activity guidelines. We examined the acute effects of cadence-controlled walking on cognition and vascular function in physically inactive older adults. In a randomized crossover design, 26 participants (65% females, 67.8 ± 11.3years) underwent 30-min acute exercise (walking at 100steps/min) and control (sitting) conditions. We measured cognition, central blood pressure (BP), and arterial stiffness before, and immediately, after each condition. We observed significant Time × Condition interactions in the Flanker Inhibitory Control and Attention (Flanker) test and Dimensional Change Card Sort (DCCS) test scores, and in central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity (p < .05). The Flanker and DCCS scores significantly increased after walking (d = 0.4 and 0.5, respectively), but not after sitting. Central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity significantly increased after sitting but remained unchanged after acute walking (d = 0.4-0.2), with p-values < .05. After walking, significant correlations were observed between DCCS and diastolic BP and central pulse pressure change scores and change scores in central pulse wave velocity,Flanker, and DCCS (rs = -0.45 to -0.52). These findings suggest that a single bout of cadence-controlled walking elicited an immediate improvement in cognition and might have mitigated increases in arterial stiffness and central BP observed in the seated control condition. Further research is needed to examine the association between cognition and vascular function following acute exercise compared to control conditions. Our findings may have practical implications for developing daily physical activity recommendations for improving the cognitive health for successful aging.

Acute inorganic nitrate ingestion does not impact oral microbial composition, cognitive function, or high-intensity exercise performance in female team-sport athletes.

The purpose of this study was to investigate the effects of acute nitrate (NO3-)-rich beetroot juice ingestion on explosive and high-intensity exercise performance, oral microbiota composition, and cognitive flexibility (i.e., function), before and after maximal intermittent running exercise. Fifteen women team-sport athletes were assigned in a randomized, double-blind, crossover design to consume concentrated NO3--depleted beetroot juice (PL; 0.1mmol NO3-) and NO3--rich beetroot juice (BR; 12.0mmol NO3-) 2.5h prior to performing a battery of exercise performance tasks and cognitive testing before and after the Yo-Yo intermittent recovery level 1 (YYIR1) running test. Resting plasma [NO3-] and plasma nitrite ([NO2-]) were elevated following BR (P < 0.001). BR did not impact global composition or relative abundance of taxa in the oral microbiome (P > 0.05) or cognitive flexibility before or after exercise (P > 0.05). There was no significant difference in performance during 20-m (PRE, PL: 4.38 ± 0.27 vs. BR: 4.38 ± 0.32s; POST, PL: 4.45 ± 0.29 vs. BR: 4.43 ± 0.35s) and 10-m sprints (PRE, PL 2.78 ± 0.15 vs. BR 2.79 ± 0.18s; POST, PL: 2.82 ± 0.16 vs. BR: 2.81 ± 0.19s), isokinetic handgrip dynamometry, medicine ball throw, horizontal countermovement jump, or YYIR1 (PL: 355 ± 163m vs. BR: 368 ± 184m) between BR and PL (P > 0.05). These findings indicate that acute dietary NO3- may not influence the oral microbiome, explosive and high-intensity exercise performance, or cognitive function in women team-sport athletes.

Bioequivalence and Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study.

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.

Pharmacokinetics of isavuconazonium sulfate and its active metabolite isavuconazole in healthy dogs.

Invasive fungal infections (IFIs) are growing in importance in veterinary and human medicine. IFIs such as aspergillosis, blastomycosis, coccidioidomycosis and histoplasmosis remain challenging to treat in dogs. Isavuconazole is a novel antifungal medication that, when compared to currently used azoles, has an expanded spectrum of antifungal activity Rudramurthy (2011), Pfaller (2013), Spec (2018), has more predictable pharmacokinetics in humans Desai (2016), Cojutti (2021) and may cause fewer side effects such as liver and renal toxicity Maertens (2016), DiPippo (2018). The pharmacokinetic profile and safety of isavuconazole in dogs has not yet been characterized. The purpose of this study was to evaluate the pharmacokinetics of isavuconazole in healthy dogs that received a single dose of the prodrug isavuconazonium sulfate. Using full crossover design, six healthy beagle dogs received isavuconazonium sulfate at a mean (+/- SD) dose of 20.6 (+/- 2.8) mg/kg orally and 21.8 (+/- 4.2) mg/kg intravenously. Plasma was collected for batched pharmacokinetic analysis of prodrug and metabolite, isavuconazole, by ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The median (Q1-Q3) maximum isavuconazole peak plasma concentration was estimated at 3,876.5 (2,811.0-4,800.0) ng/mL following oral administration, with a median (Q1-Q3) peak level at 1.3 (1.0-2.0) hours. Following intravenous administration, the median (Q1-Q3) isavuconazole peak plasma concentration was estimated at 3,221.5 (2,241.5-3,609.0) ng/mL, with a median (Q1-Q3) peak level at 0.4 (0.3-0.6) hours. The median (Q1-Q3) half-life of isavuconazole was 9.4 (7.0-12.2) hours and 14.0 (8.1-21.7) hours for oral and intravenous routes, respectively. One dog received inadvertent subcutaneous drug administration without any apparent adverse effects. Another dog experienced an anaphylactic reaction following accidental rapid drug infusion. No other drug-related adverse events were observed. At dosages used in this study, healthy dogs achieved isavuconazole plasma levels comparable to human therapeutic targets, and when properly administered the drug was well-tolerated.

Physiologic and behavioral effects of long-acting subcutaneous and transdermal buprenorphine in rats.

To investigate thermoregulation, thermal antinociception, food/kaolin intake, fecal output, and behavior following long-acting buprenorphine preparations in rats. 8 adult male rats (Rattus norvegicus) were administered long-acting SC buprenorphine (SB; 0.65 mg/kg), transdermal buprenorphine (TB; 10 mg/kg), and controls in a randomized, cross-over design. Body temperature, self-injury, sedation, food/kaolin intake, fecal output, and thermal withdrawal latencies were measured 1, 4, 8, 12, 24, 48, and 72 hours posttreatment. Data analysis was performed with mixed linear models. Self-injury was present between 1 and 12 hours and 4 and 12 hours following TB and SB, respectively; sedation was associated with TB at 12 to 24 hours. Withdrawal latencies were longer in both TB and SB groups than in the control group. Food intake decreased with time in all groups but was significantly lower 24 to 48 hours after TB and 24 to 72 hours after SB versus controls. Kaolin intake decreased from baseline 48 to 72 hours in the control group. Fecal output decreased from baseline 24 to 72 hours in all groups but was significantly lower than controls 24 hours following TB and 24 to 48 hours in SB. Body temperature increased from baseline at 1 hour, 1 to 12 hours, and 1 to 24 hours in the control, TB, and SB groups, respectively, and was significantly higher than the control group 1 to 72 hours following TB and 4 to 24 hours after SB. Transdermal buprenorphine and SB in normal rats produced antinociception, self-injurious behavior, hyperthermia, and decreased food/fecal output. Although these buprenorphine preparations may produce antinociception, untoward effects such as hyperthermia, self-injurious behavior, and reduced food intake/fecal output may be seen.

Exploring differences in patient participation in simulated emergency cases in co-located and distributed rural emergency teams – an observational study with a randomized cross-over design

BackgroundIn northern rural Sweden, telemedicine is used to improve access to healthcare and to provide patient-centered care. In emergency care during on-call hours, video-conference systems are used to connect the physicians to the rest of the team – creating ‘distributed teams’. Patient participation is a core competency for healthcare professionals. Knowledge about how distributed teamwork affects patient participation is missing.The aim was to investigate if and how teamwork affecting patient participation, as well as clinicians’ perceptions regarding shared decision-making differ between co-located and distributed emergency teams.MethodsIn an observational study with a randomized cross-over design, healthcare professionals (n = 51) participated in authentic teams (n = 17) in two scripted simulated emergency scenarios with a standardized patient: one as a co-located team and the other as a distributed team. Team performances were filmed and observed by independent raters using the PIC-ET tool to rate patient participation behavior. The participants individually filled out the Dyadic OPTION questionnaire after the respective scenarios to measure perceptions of shared decision-making. Scores in both instruments were translated to percentage of a maximum score. The observational data between the two settings were compared using linear mixed-effects regression models and the self-reported questionnaire data were compared using one-way ANOVA. Neither the participants nor the observers were blinded to the allocations.ResultsA significant difference in observer rated overall patient participation behavior was found, mean 51.1 (± 11.5) % for the co-located teams vs 44.7 (± 8.6) % for the distributed teams (p = 0.02). In the PIC-ET tool category ‘Sharing power’, the scores decreased from 14.4 (± 12.4) % in the co-located teams to 2 (± 4.4) % in the distributed teams (p = 0.001). Co-located teams scored in mean 60.5% (± 14.4) when self-assessing shared decision-making, vs 55.8% (± 15.1) in the distributed teams (p = 0.03).ConclusionsTeam behavior enabling patient participation was found decreased in distributed teams, especially regarding sharing power with the patient. This finding was also mirrored in the self-assessments of the healthcare professionals. This study highlights the risk of an increased power asymmetry between patients and distributed emergency teams and can serve as a basis for further research, education, and quality improvement.

The Effects of Caffeine on Heart Rate and Heart Rate Variability at Rest and During Submaximal Cycling Exercise

ABSTRACT The aim of this study was to investigate the effects of caffeine on heart rate and heart rate variability (HRV) at rest and during submaximal exercise. Using a balanced, double-blind, randomized, crossover design, 16 male cyclists (age: 37 ± 9 years; V ˙ O2max: 4.44 ± 0.67 L·min−1) completed three trials in an air-conditioned laboratory. In Trial 1, cyclists completed two incremental cycling tests to establish the V ˙ O2-power output relationship and V ˙ O2max. In trials 2 and 3, cyclists were evaluated for heart rate and HRV at rest, after which they ingested a capsule containing 5 mg·kg−1 of caffeine or placebo. Thirty-five minutes post-supplementation, additional resting heart rate and HRV readings were taken after which cyclists completed a submaximal incremental cycling test (6 min stages) at 40–80% of V ˙ O2max; with HR and HRV measurements taken in the last 5 min of each increment. HRV was determined from the root mean square of successive differences between R–R intervals. There were significant supplement × exercise intensity interactions on heart rate (p = .019) and HRV (p = .023), with post hoc tests on the latter showing that caffeine increased HRV at 40%, 50%, and 60% of V ˙ O2max by 3.6 ± 4.9, 2.6 ± 2.8, and 0.6 ± 1.7 ms, respectively. There was a supplement × time interaction effect on resting HRV (p < .001), but not on heart rate (p = .351). The results of this study support the suggestion that caffeine increases the parasympathetic modulation of heart rate.Clinical trial registration number: NCT05521386.

The addition of mycoprotein to a mixed-meal impacts postprandial glucose kinetics without altering blood glucose concentrations: a randomised controlled trial.

Mycoprotein is a high-fibre food previously shown to reduce postprandial glucose concentrations when ingested within a mixed-meal. We applied a dual stable isotope tracer approach to determine whether this is due to a reduced rate of appearance of glucose, in participants of ranging BMI. Twenty-four adults (F = 8, BMI 30 ± 6 kg·m-2) attended 2 trials in a double-blind, randomised, cross-over design. Participants ingested two energy and macronutrient matched milk-based drinks (enriched with 1000 mg [U-13C6] glucose in a subset of 12 participants), containing 50 g glucose and either 0 (CON) or 20 g (MYC) mycoprotein. A primed continuous intravenous infusion of D-[6,6-2H2] glucose determined plasma glucose kinetics over 6 h. Postprandial time-course, and AUC, of glucose and insulin concentration, rate of disappearance (RdT) and appearance of exogenous (RaEx), endogenous (EGP), and total (RaT) plasma glucose were assessed using two- and one-way ANOVA. Drink ingestion increased blood glucose and serum insulin concentrations (P < 0.05) and were comparable between conditions (P > 0.05). Both RaT and RdT were higher with MYC compared with CON over 6 h (mean 6 h glucose appearance and disappearance increased by 5 and 9%, respectively, P < 0.05). RaEx was not affected by MYC ingestion over 6 h (P > 0.05). The mean contribution of EGP to total glucose appearance was 15% greater with MYC, with a trend towards significance (P = 0.05). There was no relationship between BMI and the response to MYC ingestion for any of the variables (P < 0.05). The ingestion of mycoprotein within a mixed-meal impacted postprandial glucose kinetics, but not blood glucose or serum insulin concentrations, in individuals of ranging BMI. This trial was registered at clinicaltrials.gov as NCT04084639 and can be accessed at https://clinicaltrials.gov/ct2/show/NCT04084639 .

Bi-directional and multi-modal effects of dexamphetamine on spatial binding windows in healthy individuals.

Stimuli that are separated by a short window of space or time, known as spatial and temporal binding windows (SBW/TBWs), may be perceived as separate. Widened TBWs are evidenced in schizophrenia, although it is unclear if the SBW is similarly affected. The current study aimed to assess if dexamphetamine (DEX) may increase SBWs in a multimodal visuo-tactile illusion, potentially validating usefulness as an experimental model for multimodal visuo-tactile hallucinations in schizophrenia, and to examine a possible association between altered binding windows (BWs) and working memory (WM) suggested by previous research. A placebo-controlled, double-blinded, and counter-balanced crossover design was employed. Permuted block randomisation was used for drug order. Healthy participants received DEX (0.45mg/kg, PO, b.i.d.) or placebo (glucose powder) in capsules. The Rubber Hand Illusion (RHI) and Wechsler Adult Intelligence Scale Spatial Span was employed to determine whether DEX would alter SBWs and WM, respectively. Schizotypy was assessed with a variety of psychological scales. Most participants did not experience the RHI even under normal circumstances. Bi-directional and multimodal effects of DEX on individual SBWs and schizotypy were observed, but not on WM. Bidirectional multimodal effects of DEX on the RHI and SBWs were observed in individuals, although not associated with alterations in WM.

Moderate-dose caffeine enhances anaerobic performance without altering hydration status

The effects of direct nutritional supplements on athletic performance are still being investigated and arouse curiosity. Only one study in the literature was found that investigated the kicking speed performance of futsal players following low-dose caffeine supplementation (3 mg/kg); thus, the question of whether caffeine supplementation improves kicking speed as well as essential physical parameters in soccer players is still controversial. Therefore, the aim of this study was to determine the effect of caffeine supplementation on vertical jump (VJ), sprint, reaction time, balance, change of direction (COD), and ball-kicking speed in soccer players. In a double-blind, cross-over design, nine moderately trained male soccer players (21.11 ± 2.02 years, 171.22 ± 6.14 cm, 71.78 ± 10.02 kg) consumed caffeine (6 mg/kg) or a placebo 60 min before completing balance, reaction time, vertical jump, agility, 30 m sprint, and ball-kicking speed tests. Greater VJ height (p = 0.01) and power (p = 0.08), and faster completion time according to the Illinois Agility Test (p = 0.08) were found following caffeine supplementation compared to placebo. Elapsed time (p = 0.01), average (p = 0.01) time, and the slowest reaction times (p = 0.016) were significantly reduced after caffeine consumption compared to placebo supplementation. Caffeine intake significantly improved VJ, agility, and reaction time (p &amp;lt; 0.05) but did not affect 30 m sprint, ball-kicking speed, balance, and RPE values in soccer players (p &amp;gt; 0.05). Although non-significant, caffeine intake also improved sprint (0.67%) and ball kicking (2.7%) performance percentages. Also, caffeine consumption did not induce dehydration, and the athletes’ body hydration levels were normal. These findings support the use of caffeine supplementation as an effective nutritional ergogenic aid to enhance anaerobic performance, at least for vertical jumps, COD speed, and reaction time, in trained male soccer players.

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.

Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study

Background: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. Methods: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. Discussion: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.

Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study

Background: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. Methods: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. Discussion: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.

Effect of Low-Dose Mulberry Fruit Extract on Postprandial Glucose and Insulin Responses: A Randomized Pilot Trial in Individuals with Type 2 Diabetes

Adding mulberry fruit extract (MFE) to carbohydrate-rich meals can reduce postprandial glucose (PPG) and insulin (PPI) responses in healthy individuals. This pilot study assessed the acute postprandial effects of low doses of MFE in individuals with type 2 diabetes. In a randomized cross-over (within-subjects) design, 24 unmedicated adult males and females with type 2 diabetes (mean [SD] age 51.0 [9.3] yr, BMI 27.5 [3.9] kg/m2) consumed meals with 0 (control), 0.37, and 0.75 g of MFE added to ~50 g of available carbohydrates from rice. Primary and secondary outcomes were the PPG 2 hr positive incremental area under the curve and the corresponding PPI. Results were reported as mean differences from the control meal with 95% CI. Relative to control, 0.37 and 0.75 g of MFE reduced the mean 2 hr PPG by 8.2% (−20.8 to 6.6%) and 22.4% (−38.6 to −1.9%), respectively, and reduced PPI by 9.6% (−20.7 to 3.0%) and 17.5% (−27.9 to −5.7%). There were no indications of adverse events or gastrointestinal discomfort. MFE additions also led to dose-related reductions in glucose peak and glucose swing. At these levels, MFE appears to dose-dependently reduce acute PPG and PPI in individuals with type 2 diabetes and may be a feasible dietary approach to help attenuate glycemic exposures.

Effect of Low-Dose Mulberry Fruit Extract on Postprandial Glucose and Insulin Responses: A Randomized Pilot Trial in Individuals with Type 2 Diabetes

Adding mulberry fruit extract (MFE) to carbohydrate-rich meals can reduce postprandial glucose (PPG) and insulin (PPI) responses in healthy individuals. This pilot study assessed the acute postprandial effects of low doses of MFE in individuals with type 2 diabetes. In a randomized cross-over (within-subjects) design, 24 unmedicated adult males and females with type 2 diabetes (mean [SD] age 51.0 [9.3] yr, BMI 27.5 [3.9] kg/m2) consumed meals with 0 (control), 0.37, and 0.75 g of MFE added to ~50 g of available carbohydrates from rice. Primary and secondary outcomes were the PPG 2 hr positive incremental area under the curve and the corresponding PPI. Results were reported as mean differences from the control meal with 95% CI. Relative to control, 0.37 and 0.75 g of MFE reduced the mean 2 hr PPG by 8.2% (−20.8 to 6.6%) and 22.4% (−38.6 to −1.9%), respectively, and reduced PPI by 9.6% (−20.7 to 3.0%) and 17.5% (−27.9 to −5.7%). There were no indications of adverse events or gastrointestinal discomfort. MFE additions also led to dose-related reductions in glucose peak and glucose swing. At these levels, MFE appears to dose-dependently reduce acute PPG and PPI in individuals with type 2 diabetes and may be a feasible dietary approach to help attenuate glycemic exposures.

Transcranial direct current stimulation-induced changes in motor cortical connectivity are associated with motor gains following ischemic stroke.

Understanding the response of the injured brain to different transcranial direct current stimulation (tDCS) montages may help explain the variable tDCS treatment results on poststroke motor gains. Cortical connectivity has been found to reflect poststroke motor gains and cortical plasticity, but the changes in connectivity following tDCS remain unknown. We aimed to investigate the relationship between tDCS-induced changes in cortical connectivity and poststroke motor gains. In this study, participants were assigned to receive four tDCS montages (anodal, cathodal, bilateral, and sham) over the primary motor cortex (M1) according to a single-blind, randomized, crossover design. Electroencephalography (EEG) and Jebsen-Taylor hand function test (JTT) were performed before and after the intervention. Motor cortical connectivity was measured using beta-band coherence with the ipsilesional and contralesional M1 as seed regions. Motor gain was evaluated based on the JTT completion time. We examined the relationship between baseline connectivity and clinical characteristics and that between changes in connectivity and motor gains after different tDCS montages. Baseline functional connectivity, motor impairment, and poststroke duration were correlated. High ipsilesional M1-frontal-temporal connectivity was correlated with a good baseline motor status, and increased connectivity was accompanied by good functional improvement following anodal tDCS treatment. Low contralesional M1-frontal-central connectivity was correlated with a good baseline motor status, and decreased connectivity was accompanied by good functional improvement following cathodal tDCS treatment. In conclusion, EEG-based motor cortical connectivity was correlated with stroke characteristics, including motor impairment and poststroke duration, and motor gains induced by anodal and cathodal tDCS.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic–pituitary–adrenal-axis dysregulation: a study protocol description

ABSTRACT Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients – potentially with substantial exposure to early-life adversity (ELA) – show dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories. Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration. Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts. Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies. Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

Proteomic Identification and Quantification of Basal Endogenous Proteins in the Ileal Digesta of Growing Pigs

The accurate estimation of basal endogenous losses (BEL) of amino acids at the ileum is indispensable to improve nutrient utilization efficiency. This study used a quantitative proteomic approach to identify variations in BEL in the ileal digesta of growing pigs fed a nitrogen-free diet (NFD) or a casein diet (CAS). Eight barrow pigs (39.8 ± 6.3 kg initial body weight (BW)) were randomly assigned to a 2 × 2 crossover design. A total of 348 proteins were identified and quantified in both treatments, of which 101 showed a significant differential abundance between the treatments (p &lt; 0.05). Functional and pathway enrichment analyses revealed that the endogenous proteins were associated with intestinal metabolic function. Furthermore, differentially abundant proteins (DAPs) in the digesta of pigs fed the NFD enriched terms and pathways that suggest intestinal inflammation, the activation of innate antimicrobial host defense, an increase in cellular autophagy and epithelial turnover, and reduced synthesis of pancreatic and intestinal secretions. These findings suggest that casein diets may provide a more accurate estimation of BEL because they promote normal gastrointestinal secretions. Overall, proteomic and bioinformatic analyses provided valuable insights into the composition of endogenous proteins in the ileal digesta and their relationship with the functions, processes, and pathways modified by diet composition.

Proteomic Identification and Quantification of Basal Endogenous Proteins in the Ileal Digesta of Growing Pigs.

The accurate estimation of basal endogenous losses (BEL) of amino acids at the ileum is indispensable to improve nutrient utilization efficiency. This study used a quantitative proteomic approach to identify variations in BEL in the ileal digesta of growing pigs fed a nitrogen-free diet (NFD) or a casein diet (CAS). Eight barrow pigs (39.8 ± 6.3 kg initial body weight (BW)) were randomly assigned to a 2 × 2 crossover design. A total of 348 proteins were identified and quantified in both treatments, of which 101 showed a significant differential abundance between the treatments (p < 0.05). Functional and pathway enrichment analyses revealed that the endogenous proteins were associated with intestinal metabolic function. Furthermore, differentially abundant proteins (DAPs) in the digesta of pigs fed the NFD enriched terms and pathways that suggest intestinal inflammation, the activation of innate antimicrobial host defense, an increase in cellular autophagy and epithelial turnover, and reduced synthesis of pancreatic and intestinal secretions. These findings suggest that casein diets may provide a more accurate estimation of BEL because they promote normal gastrointestinal secretions. Overall, proteomic and bioinformatic analyses provided valuable insights into the composition of endogenous proteins in the ileal digesta and their relationship with the functions, processes, and pathways modified by diet composition.