Kg-1 Min-1 Research Articles

Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial.

Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT. Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (n=30) or usual care (UC; n=32). Activity comprised multicomponent exercise training (3 days/week) and sedentary time reduction (≥30 min/day) program and was delivered throughout hospitalization (≈4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake ([Formula: see text]), exercise cardiac magnetic resonance imaging for peak cardiac volume (CIpeak) and stroke volume (SVIpeak) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]). Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41-96%). There was a marked decline in [Formula: see text] in the UC program (-3.4 mL‧kg-1‧min-1 [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL‧kg-1‧min-1 [95% CI, -2.5 to 0.8]; interaction P=0.029). Activity preserved exercise cardiac function, with preservation of CIpeak (0.30 L‧min-1‧m-2 [95% CI, -0.34 to 0.41]) and SVIpeak (0.6 mL/m2 [95% CI, -1.3 to 2.5]), both of which declined with UC (CIpeak, -0.68 L‧min-1‧m-2 [95% CI, -1.3 to -0.32]; interaction P=0.008; SVIpeak, -2.7 mL/m2 [95% CI, -4.6 to -0.9]; interaction P=0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices. Multicomponent activity intervention during and after allo-SCT is beneficial for preserving patient cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT. URL: https://anzctr.org.au/; Unique identifier: ACTRN12619000741189.

Greater lactate accumulation does not alter peripheral concentrations of key appetite-regulating neuropeptides.

The potential mechanisms involved in lactate's role in exercise-induced appetite suppression requires further examination. We used sodium bicarbonate (NaHCO3) supplementation in a double-blind, placebo controlled, randomized crossover design to explore lactate's role on neuropeptide Y (NPY), agouti-related peptide (AgRP), and alpha-melanocyte stimulating hormone (α-MSH) concentrations. Twelve adults (7 males; 24.2±3.4 kg‧m-2; 42.18±8.56 mL‧kg-1‧min-1) completed two identical high-intensity interval training sessions following ingestion of NaHCO3 (BICARB) or sodium chloride (PLACEBO) pre-exercise. Blood lactate, acylated ghrelin, NPY, AgRP, α-MSH, and appetite perceptions were measured pre-exercise, 0-, 30-, 60-, and 90-min post-exercise. Free-living energy intake (electronic food diaries) was measured the day before, of, and after each experimental session. In BICARB, blood lactate was greater post-exercise (p<0.002, d>0.70) though acylated ghrelin was similar (p=0.075, =0.206) at all time-points post-exercise (p>0.034, d<0.22). NPY (p=0.006, >0.509) and AgRP (p<0.001, >0.488) had main effects of time increasing following exercise and returning to baseline, with no differences between sessions (NPY: p=0.0.192, =0.149; AgRP: p=0.422, =0.060). α-MSH had no main effect of time (p=0.573, =0.063) or session (p=0.269, =0.110). Appetite perceptions were similar during BICARB and PLACEBO (p=0.007, d=0.28) increasing in both sessions post-exercise (p<0.088, d>0.57). Energy intake had a main effect of day (p=0.025, =0.825), where the experimental session day was greater than the day before (p=0.010, d=0.59) with no other differences between days (p>0.260, d<0.38). The lower accumulation of lactate than our previous work did not generate exercise-induced appetite suppression as there were no differences in acylated ghrelin, appetite perceptions, or peripheral concentrations of neuropeptides.

The Rate of Leg Fat Oxidation Is Not Attenuated During Incremental Intensity One-Leg Knee Extensor Exercise.

It is not clear if fat oxidation is attenuated at higher exercise intensities, when exercising with a small muscle mass, and therefore, we studied leg fat oxidation during graded one-leg exercise. Ten males (age: 27 ± 2 years, body mass: 82 ± 3 kg, BMI: 24 ± 1 kg m-2, V̇O2max: 49 ± 2 mL min-1 kg-1) performed one-leg exercise at 25% of maximal workload (Wmax) for 30 min, followed by 120-min exercise at 55% Wmax with the contralateral leg, and finally 30-min exercise at 85% Wmax with the first leg. Blood was sampled from an artery and both femoral veins, and blood flow was determined using Doppler ultrasound. Muscle biopsies were obtained before and after 30 min at each workload. One-way RM ANOVA was applied to determine the impact of exercise intensity. Data are expressed as mean ± SEM. From rest through exercise average blood flow (0.4 ± 0.1, 2.1 ± 0.1, 2.6 ± 0.2, 3.7 ± 0.2 L min-1) and oxygen uptake across the leg (0.03 ± 0.01, 0.23 ± 0.02, 0.35 ± 0.03, 0.53 ± 0.04 L min-1) increased with exercise intensity (p < 0.001). Leg RQ (0.76 ± 0.04, 0.86 ± 0.02,0.87 ± 0.01, 0.92 ± 0.01, p < 0.001), leg plasma FA uptake (2 ± 2, 46 ± 8,83 ± 9, 114 ± 16 μmol min-1; p < 0.001) and rate of leg fat oxidation (0.016 ± 0.005, 0.062 ± 0.012, 0.075 ± 0.011, 0.084 ± 0.018 g min-1, p < 0.007) increased with exercise intensity. Muscle-free carnitine content was unchanged from rest at 25% Wmax and decreased after 30 min exercise at 55% and 85% Wmax (17.4 ± 1.6, 16.6 ± 0.7, 14.5 ± 1.2, 10.5 ± 1.0 mmol/kg dry muscle, respectively; p < 0.006). During incremental one-leg exercise, the rate of leg fat oxidation was not attenuated with increasing exercise intensity, probably due to an insufficient muscle metabolic stress response.

Pharmacokinetics of methadone after intravenous and subcutaneous administration in domestic ferrets (Mustela putorius furo)

ObjectiveTo determine the pharmacokinetic profile of methadone after intravenous (IV) and subcutaneous (SC) administration in domestic ferrets (Mustela putorius furo). Study designCrossover experimental study. AnimalsA group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation). MethodsMethadone hydrochloride (0.3 mg kg–1) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography–tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data. ResultsAfter IV injection, systemic clearance (Clss) and volume of distribution (Vdss) were 78.9 mL min–1 kg–1 and 9.8 L kg–1, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL–1. Behavioral changes were observed after both routes. Conclusions and clinical relevanceThe pharmacokinetic profile of IV methadone was characterized by a high Clss and large Vdss, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.

The Pleth Variability Index as a Guide to Fluid Therapy in Dogs Undergoing General Anesthesia: A Preliminary Study.

The aim of this prospective, randomized clinical trial was to evaluate the use of the pleth variability index (PVi) to guide the rate of intraoperative fluid therapy compared to a traditional fixed-fluid-rate approach in ASA 1-2 dogs undergoing surgery. Twenty-seven dogs met the inclusion criteria and were randomly assigned to the conventional fluid management group (CFM, n = 12) or the PVi-guided group (PVi, n = 15). The CFM group received a fixed rate of 5 mL kg-1 h-1 of crystalloid solution, while in the PVi group the rate was continuously adjusted based on the PVi: PVi < 14% = 3 mL kg-1 h-1; 14% ≤ PVi ≥ 20% = 10 mL kg-1 h-1; and PVi > 20% = 15 mL kg-1 h-1. Hypotension (MAP < 65 mmHg) in the CFM was treated with a maximum of two fluid boluses (5 mL kg-1 in 10 min) and in the case of no response, dobutamine (1-3 mcg kg-1 min-1) was administered. In the PVi group, the treatment of hypotension was similar, except when the PVi > 14%, when dobutamine was started directly. Total fluid volume was significantly lower in the PVI group (0.056 ± 0.027 mL kg-1 min-1) compared to the CFM group (0.132 ± 0.115 mL kg-1 min-1), and the incidence of hypotension was lower (p = 0.023) in the PVi group (0%) compared to the CFM group (41%). The mean arterial pressure (MAP) was significantly higher in the PVi group during surgery. Dobutamine was never administered in either group. Preliminary data suggest that the PVi may be considered as a potential target to guide fluid therapy in dogs; larger studies are needed, especially in cases of cardiovascular instability.

Individualized activity recommendation based on a physical fitness assessment increases short- and long-term regular physical activity in people with multiple sclerosis in a retrospective cohort study.

Despite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clinic since 2016. This study serves as retrospective quality control of this program. In a retrospective cohort study, we assessed the physical fitness of pwMS and the impact of the program on short- and long-term PA changes and behavioral determinants. The program consisted of four appointments each 2-4 weeks apart. Spiroergometric test results of female pwMS were compared to female non-MS controls who underwent a voluntary physical fitness analysis. The short version of the Freiburger questionnaire, self-developed questions and the modified Physical activity screening questionnaire (PASQ) were sent to all participants assessing the PA levels before the program, 3 months after the program (short-term), and at the time of the survey (long-term). Additionally, established questionnaires assessed behavioral determinants before the program and long-term. A total of 166 participants [mean age 38.32 (± 10.61 SD), mean EDSS 2.30 (±1.29 SD)] and mostly females (63.3%, n = 105) were included in the study and started the program. A total of 136 participants completed the program. Out of these 63.9% (n = 87) answered the questionnaires in 12.38 (±11.34 SD) months after finishing the program. At baseline female pwMS (n = 100) showed a lower physical fitness in comparison to non-MS controls (n = 26) (maximal workload (Watts): 138.86 ± 37.85 vs. 191.73 ± 45.25, p < 0.001; peak oxygen consumption (ml min-1 kg-1): 26.40 ± 7.23 vs. 31.56 ± 10.10, p = 0.020). pwMS were more regularly active in short- (62.1%) and long-term (55.2%) compared to baseline (24.2%, p < 0.001). Among the activated participants, we observed improved internal motivation (p = 0.002) and decreased perception of barriers (p = 0.006) compared to baseline. PwMS showed a lower physical fitness in comparison to non-MS controls. An individually tailored PA promotion program might improve behavioral determinants and thereby increase short- and long-term PA levels of pwMS.

Comparison of Propofol and Sevoflurane Anaesthesia in Terms of Postoperative Nausea-Vomiting Complication in Cardiac Surgery Patients Undergoing Enhanced Recovery After Surgery Protocol: A Prospective Randomized Study.

Postoperative nausea (PN) and vomiting (PONV) in cardiac surgery increases adrenergic stimulation, limits mobilization and oral intake, and can be distressing for patients. The primary aim of our study was to investigate the effect of sevoflurane and propofol anaesthesia on the incidence of PONV in cardiac surgery patients undergoing Enhanced Recovery After Surgery (ERAS) protocol. Following ethics committee approval, 62 patients undergoing elective coronary artery bypass surgery with ERAS protocol were included in this prospective randomized study. After standard induction of anaesthesia, Group S received 1.5-2% sevoflurane and Group P received 50-100 μg kg-1 min-1 propofol infusion as maintenance anaesthetic agent with a bispectral index of 40-50. The incidence of PN and PONV between 0-6 hours (early) and 6-24 hours (late) after extubation was compared as the primary outcome. The incidence of delirium was analyzed as a secondary outcome for similar periods. In the propofol group, 3 patients were excluded due to postoperative tamponade revision and prolonged mechanical ventilation. PN in the early post-extubation period (29% vs. 7.1%, P=0.031) was significantly higher in Group S. The incidence of delirium was similar between the groups in both periods. Propofol may reduce the incidence of PN in the first 6 hours after extubation compared with sevoflurane. We believe that this period will be beneficial for gastrointestinal tolerance as it is the period when oral intake is initiated in patients. In conclusion, propofol maintenance in cardiac surgery patients may facilitate patient rehabilitation as part of the ERAS protocol.

Physical fitness assessment of a Venezuelan industrial direct labor force population

Introduction The purpose of this research is to evaluate the physical fitness variables of Venezuelan workers, taking into account exercise batteries or submaximal tests that have been little used in the industrial environment.Methods: A quantitative, descriptive, cross-sectional, epidemiological and field study was conducted in a Venezuelan population of industrial direct labor workers in bipedestation. The sample consisted of 185 workers (M: 136, W: 49) in the main industrial areas of the state of Aragua-Venezuela.Results: Results were obtained on the physical fitness of Venezuelan industrial direct labor workers presenting average results in both sexes. Calculations for obtaining HRmax and RAC in ml O2 min-1 kg-1 were taken into account.Conclusions: A population of industrial direct labor was observed, of low physical capacity with values associated with age (42.87 M-38.43W), physical wear and tear, poor physical fitness habits, poor dietary habits and decrease in muscle mass.

Propofol-sparing and hemodynamic effects of guaifenesin in sheep

ObjectiveTo evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep. Study designProspective, blinded, two-way crossover experimental study. AnimalsThirteen healthy adult female sheep. MethodsAnesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg–1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg–1 min–1). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student’s t-test. Values of p < 0.05 were considered statistically significant. ResultsThe propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg–1) than in the SAL treatment (5.94 ± 1.09 mg kg–1). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments. Conclusions and clinical relevanceGuaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range.

Handcycling with concurrent lower body low-frequency electromyostimulation significantly increases acute oxygen uptake in elite wheelchair basketball players: an acute crossover trial.

Wheelchair basketball (WCB) demands high-intensity training due to its intermittent nature. However, acute oxygen uptake (V˙O2) in handcycling is restricted. Combining handcycling with low-frequency electromyostimulation (LF-EMS) may enhance V˙O2 in elite WBC athletes. Randomized crossover trail. Twelve German national team WCB players (age: 25.6 [5.6] years, height: 1.75 [0.16] m, mass: 74.0 [21.7] kg, classification: 2.92 [1.26]). Participants underwent 2×5 min of handcycling (60 rpm, ¾ bodyweight resistance in watts) (HANDCYCLE) and 2×5 min of handcycling with concurrent LF-EMS (EMS_HANDCYCLE). LF-EMS (4Hz, 350µs, continuous stimulation) targeted gluteal, quadriceps, and calf muscles, adjusted to individual pain thresholds (buttocks: 69.5 [22.3] mA, thighs: 66.8 [20.0] mA, calves: 68.9 [31.5] mA). Significant mode-dependent differences between HANDCYCLE and EMS_HANDCYCLE were found in V˙O2 (17.60 [3.57] vs 19.23 [4.37] ml min-1 kg-1, p = 0.001) and oxygen pulse (16.69 [4.51] vs 18.41 [5.17] ml, p = 0.002). ΔLactate was significantly lower in HANDCYCLE (0.04 [0.28] vs 0.31 [0.26] mmol l-1). Although perceived effort did not differ (p = 0.293), discomfort was rated lower in HANDCYCLE (1.44 [1.28] vs 3.94 [2.14], p = 0.002). LF-EMS applied to the lower extremities increases oxygen demand during submaximal handcycling. Thus, longitudinal application of LF-EMS should be investigated as a potential training stimulus to improve aerobic capacity in wheelchair athletes.

Evaluating Airflow Sensor Methods: Precision in IndirectCalorimetry.

This study assesses the impact of three volumetric gas flow measurement methods-turbine (fT); pneumotachograph (fP), and Venturi (fV)-on predictive accuracy and precision of expired gas analysis indirect calorimetry (EGAIC) across varying exercise intensities. Six males (Age: 38 ± 8 year; Height: 178.8 ± 4.2 cm; : 42 ± 2.8 mL O2 kg-1 min-1) and 14 females (Age = 44.6 ± 9.6 year; Height = 164.6 ± 6.9 cm; = 45 ± 8.6 mL O2 kg-1 min-1) were recruited. Participants completed physical exertion on a stationary cycle ergometer for simultaneous pulmonary minute ventilation ( ) measurements and EGAIC computations. Exercise protocols and subsequent conditions involved a 5-min cycling warm-up at 25 W min-1, incremental exercise to exhaustion ( ramp test), then a steady-state exercise bout induced by a constant Watt load equivalent to 80% ventilatory threshold (80% VT). A linear mixed model revealed that exercise intensity significantly affected measurements (p < 0.0001), whereas airflow sensor method (p = 0.97) and its interaction with exercise intensity (p = 0.91) did not. Group analysis of precision yielded a CV % = 21%; SEM = 5 mL O2 kg-1 min-1. Intra- and interindividual analysis of precision via Bland-Altman revealed a 95% confidence interval (CI) precision benchmark of 3-5 mL kg-1 min-1. Agreement among methods decreased at power outputs eliciting up to 150 L min-1, indicating a decrease in precision and highlighting potential challenges in interpreting biological variability, training response heterogeneity, and test-retest comparisons. These findings suggest careful consideration of airflow sensor method variance across metabolic cart configurations.

Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

Longitudinal changes in anthropometric, physiological, and physical qualities of international women's rugby league players.

This is the first study to assess longitudinal changes in anthropometric, physiological, and physical qualities of international women's rugby league players. Thirteen forwards and 11 backs were tested three times over a 10-month period. Assessments included: standing height and body mass, body composition measured by dual x-ray absorptiometry (DXA), a blood panel, resting metabolic rate (RMR) assessed by indirect calorimetry, aerobic capacity (i.e.,[Formula: see text]) evaluated by an incremental treadmill test, and isometric force production measured by a force plate. During the pre-season phase, lean mass increased significantly by ~2% for backs (testing point 1: 47 kg; testing point 2: 48 kg) and forwards (testing point 1: 50 kg; testing point 2: 51 kg) (p = ≤ 0.05). Backs significantly increased their [Formula: see text] by 22% from testing point 1 (40 ml kg-1 min-1) to testing point 3 (49 ml kg-1 min-1) (p = ≤ 0.04). The [Formula: see text] of forwards increased by 10% from testing point 1 (41 ml kg-1 min-1) to testing point 3 (45 ml kg-1 min-1), however this change was not significant (p = ≥ 0.05). Body mass (values represent the range of means across the three testing points) (backs: 68 kg; forwards: 77-78 kg), fat mass percentage (backs: 25-26%; forwards: 30-31%), resting metabolic rate (backs: 7 MJ day-1; forwards: 7 MJ day-1), isometric mid-thigh pull (backs: 2106-2180 N; forwards: 2155-2241 N), isometric bench press (backs: 799-822 N; forwards: 999-1024 N), isometric prone row (backs: 625-628 N; forwards: 667-678 N) and bloods (backs: ferritin 21-29 ug/L, haemoglobin 137-140 g/L, iron 17-21 umol/L, transferrin 3 g/L, transferring saturation 23-28%; forwards: ferritin 31-33 ug/L, haemoglobin 141-145 g/L, iron 20-23 umol/L, transferrin 3 g/L, transferrin saturation 26-31%) did not change (p = ≥ 0.05). This study provides novel longitudinal data which can be used to better prepare women rugby league players for the unique demands of their sport, underpinning female athlete health.

Evaluating the Efficacy of a Peripheral Nerve Simulator-Guided Brachial Plexus Block in Rabbits Undergoing Orthopaedic Surgery Compared to Systemic Analgesia.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided brachial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl, and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 mL kg-1), and eight received a lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 min-1). Rescue analgesia was provided with fentanyl IV. Carprofen was administered at the end of the surgery. Postoperative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered according to the pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to none in BPB. However, rabbits in both groups had similar pain scores, and there was no difference in the administration of postoperative analgesia. There were no significant differences in food intake or faeces production over 18 h, and no significant differences in distance travelled or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively, both groups were comparable.

Day-to-Day Glycemic Variability Using Continuous Glucose Monitors in Endurance Athletes.

The application of continuous glucose monitors (CGMs) to measure interstitial glucose in athletic populations is limited by the lack of accepted athlete-specific reference values. The aim of this study was to develop athlete-specific reference ranges for glycemic variability under standardized diet and exercise conditions. A total of 12 elite racewalkers (n = 7 men, 22.4 ± 3.5 years, VO2max 61.6 ± 7.3 mL kg-1 min-1) completed two 4-d trials separated by 4-d. Athletes were provided a high-energy, high-carbohydrate diet (225 ± 1.6 kJ kg-1 day-1, 8.4 ± 0.3 g kg-1 day-1 carbohydrate) and completed standardized daily exercise. The timing of food consumed and exercise undertaken were matched each day across the 4-d trials. Interstitial glucose data were collected via Freestyle Libre 2 CGMs. Glycemic variability was calculated as the mean amplitude of glycemic excursions (MAGEs), mean of daily differences (MODD), and standard deviation (SD). Twenty-four hour MODD, MAGE, and SD for interstitial glucose were 12.6 ± 1.8 mg/dL (0.7 ± 0.1 mmol/L), 36.0 ± 5.4 mg/dL (2.0 ± 0.3 mmol/L), and 16.2 ± 1.8 mg/dL (0.9 ± 0.1 mmol/L), respectively. Twenty-four hour mean glucose (MG; 102.6 ± 5.4 mg/dL [5.7 ± 0.3 mmol/L]) was higher than overnight (91.8 ± 5.4 mg/dL [5.1 ± 0.3 mmol/L]; P < .0001) and was lower in women than men (99.0 ± 3.6 mg/dL [5.5 ± 0.2 mmol/L] vs 104.4 ± 3.6 mg/dL [5.8 ± 0.2 mmol/L]; P = .059, d = 1.4). This study provides reference indices under standardized diet and exercise conditions for glycemic variability derived from CGMs in endurance athletes which are similar than previously reported for healthy individuals, despite strenuous daily training and a high daily energy and carbohydrate diet.

Horizontal running inside circular walls of Moon settlements: a comprehensive countermeasure for low-gravity deconditioning?

Long-lasting exposure to low gravity, such as in lunar settlements planned by the ongoing Artemis Program, elicits muscle hypotrophy, bone demineralization, cardio-respiratory and neuro-control deconditioning, against which optimal countermeasures are still to be designed. Rather than training selected muscle groups only, 'whole-body' activities such as locomotion seem better candidates, but at Moon gravity both 'pendular' walking and bouncing gaits like running exhibit abnormal dynamics at faster speeds. We theoretically and experimentally show that much greater self-generated artificial gravities can be experienced on the Moon by running horizontally inside a static 4.7 m radius cylinder (motorcyclists' 'Wall of Death' of amusement parks) at speeds preventing downward skidding. To emulate lunar gravity, 83% of body weight was unloaded by pre-tensed (36 m) bungee jumping bands. Participants unprecedentedly maintained horizontal fast running (5.4-6.5 m s-1) for a few circular laps, with intense metabolism (estimated as 54-74 mlO2 kg-1 min-1) and peak forces during foot contact, inferred by motion analysis, of 2-3 Earth body weight (corresponding to terrestrial running at 3-4 m s-1), high enough to prevent bone calcium resorption. A training regime of a few laps a day promises to be a viable countermeasure for astronauts to quickly combat whole-body deconditioning, for further missions and home return.

Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters

IntroductionDiabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. Methods and materialsStems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). ResultsThe characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36 μg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of −81.48 Kcal mol−1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of −3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min−1 kg−1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. ConclusionThe data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Sedation for Colonoscopy Procedures Using Dexmedetomidine Versus Propofol-Fentanyl Infusions: A Prospective Randomized Controlled Trial.

Different anaesthetists for sedation or monitored anaesthesia care have been used for colonoscopy. The target of this research was the ability to perform colonoscopy under a painless degree of sedation and the prevalence of undesired proceedings. A total of 60 patients were randomly divided into two groups: Group D received dexmedetomidine and Group PF received propofol-fentanyl. Patients in both groups received the same infusion ratio. The minimum infusion amount of dexmetatomidine is (0.1 to 0.4 μg kg-1 h-1) in Group D, whereas fentanyl is administered at a rate of 0.01 to 0.05 μg kg-1 min-1 in the PF group during the approximately 45-min colonoscopy. Group D exhibited significantly lower modified Observer's Assessment of Alertness/Sedation (OAA/S) scores at intraoperative time points T1-T12. Group D also exhibited significantly lower visual analog scale scores for pain at intraoperative time points T4 and T7. The mean arterial pressure was significantly lower in Group D at intraoperative times T6-T8 and T11-T12, as well as upon admission to the post-anaesthesia care unit (PACU) and 30 min after admission to the PACU. The results of the ANOVA tests revealed a significantly lower heart rate in Group D. The respiratory rate exhibited a notable decrease during time intervals T8 and T10 in the PF group. The administration of dexmetatomidine and propofol-fentanyl during colonoscopy was found to be safe. In addition, dexmetatomidine may present significant benefits in this context because of its lower occurrence of adverse respiratory events.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Histamine H2-receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II–hypertensive mice

Aldosterone through the mineralocorticoid receptor MR has detrimental effects on cardiovascular disease. It reduces the bioavailability of nitric oxide and impairs endothelium-dependent vasodilatation. In resistance arteries, aldosterone impairs the sensitivity of vascular smooth muscle cells to nitric oxide by promoting the local secretion of histamine which activates H2 receptors. The present experiments tested in vivo and ex vivo the hypothesis that systemic H2-receptor antagonism reduces arterial blood pressure and improves vasodilatation in angiotensin II–induced chronic hypertension. Hypertension was induced by intravenous infusion of angiotensin II (60 ng kg−1 min−1) in conscious, unrestrained mice infused concomitantly with the H2-receptor antagonist ranitidine (27.8 µg kg−1 min−1) or vehicle for 24 days. Heart rate and arterial blood pressure were recorded by indwelling arterial catheter. Resistance (mesenteric) and conductance (aortae) arteries were harvested for perfusion myography and isometric tension recordings by wire myography, respectively. Plasma was analyzed for aldosterone concentration. ANGII infusion resulted in elevated arterial blood pressure and while in vivo treatment with ranitidine reduced plasma aldosterone concentration, it did not reduce blood pressure. Ranitidine improved ex vivo endothelial function (acetylcholine 10−9 to 10−6 mol L−1) in mesenteric resistance arteries. This was abolished by ex vivo treatment with aldosterone (10−9 mol L−1, 1 h). In aortic segments, in vivo ranitidine treatment impaired relaxation. Activation of histamine H2 receptors promotes aldosterone secretion, does not affect arterial blood pressure, and protects endothelial function in conduit arteries but promotes endothelial dysfunction in resistance arteries during angiotensin II–mediated hypertension. Aldosterone contributes little to angiotensin II–induced hypertension in mice.