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Creatine (Cr) supplementation increases muscle mass, strength, and power. Arginine [alpha]-ketoglutarate (A-AKG) is a precursor for nitric oxide production and has the potential to improve blood flow and nutrient delivery (i.e., Cr) to muscles. This study compared a commercial dietary supplement of Cr, A-AKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with Cr alone or placebo on exercise performance and body composition. Thirty-five men (~23 yr) were randomized to Cr + A-AKG (0.1 g · kg[-1] · d[-1] Cr + 0.075 g · kg[-1] · d[-1] A-AKG, n = 12), Cr (0.1 g · kg[-1] · d[-1], n = 11), or placebo (1 g · kg[-1] · d[-1] sucrose, n = 12) for 10 d. Body composition, muscle endurance (bench press), and peak and average power (Wingate tests) were measured before and after supplementation. Bench-press repetitions over 3 sets increased with Cr + A-AKG (30.9 +/- 6.6 --> 34.9 +/- 8.7 reps; p < .01) and Cr (27.6 +/- 5.9 --> 31.0 +/- 7.6 reps; p < .01), with no change for placebo (26.8 +/- 5.0 --> 27.1 +/- 6.3 reps). Peak power significantly increased in Cr + A-AKG (741 +/- 112 --> 794 +/- 92 W; p < .01), with no changes in Cr (722 +/- 138 --> 730 +/- 144 W) and placebo (696 +/- 63 --> 705 +/- 77 W). There were no differences in average power between groups over time. Only the Cr-only group increased total body mass (79.9 +/- 13.0 --> 81.1 +/- 13.8 kg; p < .01), with no significant changes in lean-tissue or fat mass. These results suggest that Cr alone and in combination with A-AKG improves upper body muscle endurance, and Cr + A-AKG supplementation improves peak power output on repeated Wingate tests. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effects of Red Bull energy drink on Wingate cycle performance and muscle endurance. Healthy young adults (N = 15, 11 men, 4 women, 21 ± 5 y old) participated in a crossover study in which they were randomized to supplement with Red Bull (2 mg/kg body mass of caffeine) or isoenergetic, isovolumetric, noncaffeinated placebo, separated by 7 d. Muscle endurance (bench press) was assessed by the maximum number of repetitions over 3 sets (separated by 1-min rest intervals) at an intensity corresponding to 70% of baseline 1-repetition maximum. Three 30-s Wingate cycling tests (load = 0.075 kp/kg body mass), with 2 min recovery between tests, were used to assess peak and average power output. Red Bull energy drink significantly increased total bench-press repetitions over 3 sets (Red Bull = 34 ± 9 vs. placebo = 32 ± 8, P < 0.05) but had no effect on Wingate peak or average power (Red Bull = 701 ± 124 W vs. placebo = 700 ± 132 W, Red Bull = 479 ± 74 W vs. placebo = 471 ± 74 W, respectively). Red Bull energy drink significantly increased upper body muscle endurance but had no effect on anaerobic peak or average power during repeated Wingate cycling tests in young healthy adults. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether low-dose creatine and protein supplementation during resistance training (RT; 3 d·wk[-1]; 10 wk) in older men (59-77 yr) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites (formaldehyde). Methods: Older men were randomized (double-blind) to receive 0.1 g·kg[-1] creatine + 0.3 g·kg[-1] protein (CP; n = 10), creatine (C; n = 13), or placebo (PLA; n = 12) on training days. Measurements before and after RT included lean tissue mass (air-displacement plethysmography), muscle thickness (ultrasound) of elbow, knee, and ankle flexors and extensors, leg and bench press strength, and urinary indicators of cytotoxicity (formaldehyde), myofibrillar protein degradation [3-methylhistidine (3-MH)],and bone resorption [cross-linked N-telopeptides of type I collagen (NTx)]. Results: Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA (P < 0.05). Subjects who received CP increased lean tissue mass (+5.6%) more than C (+2.2%) or PLA (+1.0%; P < 0.05) and increased bench press strength (+25%) to a greater extent than C and PLA combined (+12.5%; P < 0.05). CP and C did not differ from PLA for changes in formaldehyde production (+24% each). Subjects receiving creatine (C and CP) experienced a decrease in 3-MH by 40% compared with an increase of 29% for PLA (P < 0.05) and a reduction in NTx (-27%) versus PLA (+13%; P = 0.05). Conclusions: Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength. Low-dose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production. [ABSTRACT FROM AUTHOR]

The loss of medullary control of spinal circuits controlling the heart and blood vessels is a unifying mechanism linking both hemodynamic instability and the risk for cardiovascular diseases (CVD) following spinal cord injury (SCI). As such, new avenues to regulate sympathetic activity are essential to mitigate CVD in this population. Acute intermittent hypoxia (AIH) induces a type of neuroplasticity known as long-term facilitation (LTF), a persistent increase in nerve activity post-AIH in spinal motor circuits. Whether LTF occurs within the sympathetic circuit following SCI is largely unknown. We aimed to test whether AIH elicits sympathetic LTF (i.e., sLTF) and attenuates hypoactivity in sub-lesional splanchnic sympathetic circuits in a male rat model of SCI. In 3 experimental series, we tested whether 1) high-thoracic contusion SCI induces hypoactivity in splanchnic sympathetic nerve activity, 2) AIH elicits sLTF following SCI, and 3) sLTF requires carotid chemoreflex activation or spinal cord tissue hypoxia. Our results indicate that a single-session of AIH therapy (10 × 1 min of F i O 2  = 0.1, interspersed with 2 min of F i O 2  = 1.0) delivered at 2 weeks following SCI attenuates SCI-induced sympathetic hypoactivity by eliciting sLTF 90 min post-treatment that is independent of peripheral chemoreflex activation and/or spinal cord hypoxia. These findings advance our mechanistic understanding of AIH in the field and yield new insights into factors underpinning AIH-induced sLTF following SCI in a rat model. Our findings also set the stage for the chronic application of AIH to alleviate secondary complications resulting from sympathetic hypoactivity following SCI., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, products, or services that may be related to the subject matter of the article., (Copyright © 2024. Published by Elsevier Inc.)

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit increased food intake and body weight following exogenous ketone ester supplementation or a ketogenic diet. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, enzymatic amino acid BHB-ylation defines a ketone shunt pathway and bioactive ketone metabolites linked to energy balance., Competing Interests: Declaration of interests A provisional patent application has been filed by Stanford University on BHB-amino acids for the treatment of cardiometabolic disease., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes (T2D) is preceded by prediabetes, and these conditions place a great burden on patients and society. These conditions are significantly associated with poor glycemic control, which is improved by resistance exercise. It has been suggested that resistance exercise should be performed with a high degree of effort to improve glucose metabolism, but this is associated with negative psychological responses that might lead to lower long-term adherence., Objective: This study aimed to investigate the effect of the degree of effort during a resistance exercise session on glycemic control and psychological responses in individuals living with prediabetes or T2D., Methods: This study will be a crossover, 3-arm, randomized controlled trial. A total of 15 participants living with prediabetes or T2D will be thoroughly familiarized with 7 resistance exercises; afterward, they will perform 3 randomized experimental sessions, each lasting approximately 48 hours each, separated by at least 4 washout days. In 2 of these sessions, supervised resistance exercise will be performed, but the sessions will differ in the degree of effort in each set (high vs low) and will be equalized in terms of total weight lifted and session duration. For this, proximity to failure will be manipulated by changing the number of sets per exercise, the number of repetitions per set, and the resting interval between sets and exercises. Participants will also complete a sedentary (control) session, where they will not perform any exercise. In response to each session, psychological responses will be assessed (exertion, affect, enjoyment, self-efficacy, and discomfort). Glycemic control will be assessed by a continuous glucose monitoring device every 5 minutes, throughout the approximately 48 hours of each experimental session. Food and drink will be individually prescribed by a registered dietitian nutritionist and provided to participants, in order to control for the confounding effect of energy intake and diet composition. Physical activity levels will be assessed by accelerometry. Randomization will be done using the opaque, sequentially numbered envelopes technique. Participants and researchers will be blinded for continuous glucose monitoring and accelerometry data, and data will be analyzed by a blinded statistician., Results: This study has been funded, and data collection is expected to take place between June 2024 and May 2025. Final manuscript submission should happen by August 2025., Conclusions: The results of this project might encourage individuals living with prediabetes and T2D to engage in resistance exercise while better informing exercise specialists on how to best incorporate resistance exercise in their client's or patient's routine., Trial Registration: ClinicalTrials.gov NCT06208189; https://clinicaltrials.gov/study/NCT06208189., International Registered Report Identifier (irrid): PRR1-10.2196/63598., (©Marissa Ramirez, Maja Gebauer, Christine Mermier, Jonathan Peter Little, Luotao Lin, Gabriel Palley, Yu Yu Hsiao, Roberto Ivan Mota Alvidrez, Zach A Mang, Fabiano Trigueiro Amorim, Valmor Tricoli, Flavio De Castro Magalhaes. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.11.2024.)

Introduction: Changes in plasma concentrations of anti-inflammatory cytokines, such as interleukin-6 (IL-6) and IL-10, after acute resistance exercise (RE) have been widely explored. Whether observed changes in plasma cytokine concentration correspond to the activation of anti-inflammatory signaling pathways in immune cells after acute RE is unknown. This study aimed to determine if changes in plasma cytokines after acute RE resulted in the activation of anti-inflammatory signaling pathways in peripheral blood mononuclear cells (PBMC)., Methods: Healthy young males (N = 16; age = 23.5 ± 2.7 yr; BMI = 22.4 ± 1.7 kg·m-2) participated in a single session of whole-body RE (4 sets of 4 different exercises at 70% 1-repetition maximum with the last set to failure) and a sedentary control (CON) condition in a randomized crossover design. Blood samples were collected at several time points before and after the exercise bout., Results: Higher plasma IL-6, IL-10, and IL-1 RA concentrations were observed after RE compared with CON. Phosphorylation of STAT3 and protein expression of SOCS3 in PBMC were increased in RE compared with CON. The elevation of plasma IL-6, but not IL-10, coincided with the activation of STAT3 signaling in PBMC., Conclusions: These results highlight a potential mechanism by which RE may exert anti-inflammatory actions in circulating immune cells., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Although the efficacy of interval training for improving body composition has been summarized in an increasing number of systematic reviews in recent years, discrepancies in review findings and conclusions have been observed., Objective: This study aims to synthesize the available evidence on the efficacy of interval training compared with moderate-intensity continuous training (MICT) and nonexercise control (CON) in reducing body adiposity in apparently healthy adults., Methods: An umbrella review with meta-analysis was performed. A systematic search was conducted in seven databases (MEDLINE, EMBASE, Cochrane Database, CINAHL, Scopus, SPORTDiscus, and Web of Science) up to October 2023. Systematic reviews with meta-analyses of randomized controlled trials (RCTs) comparing interval training and MICT/CON were included. Literature selection, data extraction, and methodological quality assessment (AMSTAR-2) were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model. Subgroup analyses were conducted based on the type of interval training [high-intensity interval training (HIIT) and sprint interval training (SIT)], intervention duration, body mass index, exercise modality, and volume of HIIT protocols., Results: Sixteen systematic reviews, including 79 RCTs and 2474 unique participants, met the inclusion criteria. Most systematic reviews had a critically low (n = 6) or low (n = 6) AMSTAR-2 score. Interval training demonstrated significantly greater reductions in total body fat percent (BF%) compared with MICT [weighted mean difference (WMD) of - 0.77%; 95% confidence interval (CI) - 1.12 to - 0.32%] and CON (WMD of - 1.50%; 95% CI - 2.40 to - 0.58%). Significant reductions in fat mass, visceral adipose tissue, subcutaneous abdominal fat, and android abdominal fat were also observed following interval training compared to CON. Subgroup analyses indicated that both HIIT and SIT resulted in superior BF% loss than MICT. These benefits appeared to be more prominent in individuals with overweight/obesity and longer duration interventions (≥ 12 weeks), as well as in protocols using cycling as a modality and low-volume HIIT (i.e., < 15 min of high-intensity exercise per session)., Conclusions: This novel umbrella review with large-scale meta-analysis provides an updated synthesis of evidence with implications for physical activity guideline recommendations. The findings support interval training as a viable exercise strategy for reducing adiposity in the general population., Competing Interests: Declarations Funding This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest All authors have no conflicts of interest to disclose. Availability of data and material The datasets analyzed in this review are available from the corresponding author on reasonable request. Code availability Not applicable. Author contributions E.P., J.L., S.W., and R.H. conceived the idea for the review. E.P., J.L., and R.H. conducted the search, study selection, data extraction, and quality assessment. E.P., J.L., and R.H. drafted the initial manuscript. E.P., J.L., and R.H. contributed to writing the manuscript. All authors reviewed and approved the final manuscript., (© 2024. The Author(s).)

Purpose: Identification of adolescent idiopathic scoliosis (AIS) patients with mild curvatures who pose significant risk of progressing to severe levels of curvatures is of paramount importance for clinical care. This study aimed to compare segmental deformity changes in AIS sub-cohorts that are dichotomised by progression status., Methods: Thirty-six female participants with Lenke 1 AIS curves were investigated with sequential MRIs during growth. Scans were reformatted to measure orthogonal segmental parameters, including sagittal/coronal wedging angles and axial rotation angles. Participants were dichotomised by progression. Two-tailed, independent sample t-tests were used to compare sub-cohort multi-segmental and segmental deformity parameters. Measurements were compared at each scan number and variable rates of change were determined using actual time between measures., Results: AIS progression status sub-cohorts were comparable at scan 1 for multi-segmental deformity parameters (e.g. major thoracic curve angle, rib hump, kyphosis) (P > 0.05). However, apical measures of coronal IVD wedging, axial IVD rotation and axial vertebral rotation were segmental parameters at scan 1 which were larger for participants whose AIS would later go on to clinically progress (all P < 0.05). Measures of segmental hypokyphosis were comparable between groups. As development was tracked at each subsequent scan, coronal and axial plane differences between groups increased in both magnitude and number of differences., Conclusion: Initial disparity and then subsequent increasing magnitude of change of axial rotation may indicate a higher propensity to clinically progress in the future. This knowledge hopes to provide useful management information for AIS care providers and prognostic education for patients alike., Level of Evidence: II., (© 2024. The Author(s).)

Transcranial Ultrasound Stimulation (TUS) can noninvasively and reversibly perturb neuronal activity, but the mechanisms by which ultrasound engages brain circuits to induce functional effects remain unclear. To elucidate these interactions, we applied TUS to the cortex of awake mice and concurrently monitored local neural activity at the acoustic focus with two-photon calcium imaging. We show that TUS evokes highly focal responses in three canonical neuronal populations, with cell-type-specific dose dependencies. Through independent parametric variations, we demonstrate that evoked responses collectively scale with the time-average intensity of the stimulus. Finally, using computational unmixing we propose a physiologically realistic cortical circuit model that predicts TUS-evoked responses as a result of both direct effects and local network interactions. Our results provide a first direct evidence of TUS's focal effects on cortical activity and shed light on the complex circuit mechanisms underlying these effects, paving the way for TUS's deployment in clinical settings.

β-hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve interconversion of BHB and primary energy intermediates. Here we show that CNDP2 controls a previously undescribed secondary BHB metabolic pathway via enzymatic conjugation of BHB and free amino acids. This BHB-ylation reaction produces a family of endogenous ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. Administration of BHB-Phe, the most abundant BHB-amino acid, to obese mice activates neural populations in the hypothalamus and brainstem and suppresses feeding and body weight. Conversely, CNDP2-KO mice exhibit increased food intake and body weight upon ketosis stimuli. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, the metabolic pathways of BHB extend beyond primary metabolism and include secondary ketone metabolites linked to energy balance., Competing Interests: Declaration of interests A provisional patent application has been filed by Stanford University on BHB-amino acids for the treatment of cardiometabolic disease.

Infection control measures to prevent viral and bacterial infection spread are critical to maintaining a healthy environment. Pathogens such as viruses and pyogenic bacteria can cause infectious complications. Viruses such as SARS-CoV-2 are known to spread through the aerosol route and on fomite surfaces, lasting for a prolonged time in the environment. Developing technologies to mitigate the spread of pathogens through airborne routes and on surfaces is critical, especially for patients at high risk for infectious complications. Multifunctional coatings with a broad capacity to bind pathogens that result in inactivation can disrupt infectious spread through aerosol and inanimate surface spread. This study uses C-POLAR, a proprietary cationic, polyamine, organic polymer with a charged, dielectric property coated onto air filtration material and textiles. Using both SARS-CoV-2 live viral particles and bovine coronavirus models, C-POLAR-treated material shows a dramatic 2-log reduction in circulating viral inoculum. This reduction is consistent in a static room model, indicating simple airflow through a static C-POLAR hanging can capture significant airborne particles. Finally, Gram-positive and Gram-negative bacteria are applied to C-POLAR textiles using a viability indicator to demonstrate eradication on fomite surfaces. These data suggest that a cationic polymer surface can capture and eradicate human pathogens, potentially interrupting the infectious spread for a more resilient environment., Importance: Infection control is critical for maintaining a healthy home, work, and hospital environment. We test a cationic polymer capable of capturing and eradicating viral and bacterial pathogens by applying the polymer to the air filtration material and textiles. The data suggest that the simple addition of cationic material can result in the improvement of an infectious resilient environment against viral and bacterial pathogens., Competing Interests: The authors declare no conflict of interest.

Little is known about the physiological and biomechanical factors that determine individual preferences in lying posture during sleep. This study investigated relationships between position preference and position-specific arousals, awakenings, limb movements and limb movement arousals to explore the mechanisms by which biomechanical factors influence position preference. Forty-one mature-aged adults underwent 2 nights of at-home polysomnography ~2 weeks apart, on a standardised firm foam mattress, measuring nocturnal sleep architecture and position. The lateral supine ratio and restlessness indices specific to lateral and supine positions including limb movement index, limb movement arousal index, arousal index, wake index, respiratory arousal index and apnea-hypopnea index were calculated and analysed via linear mixed-effects regression. In the supine position, all restlessness indices were significantly increased compared with the lateral position, including a 379% increase in respiratory arousals (β = 7.0, p < 0.001), 108% increase in arousal index (β = 10.3, p < 0.001) and 107% increase in wake index (β = 2.5, p < 0.001). Wake index in the supine position increased significantly with more lateral sleep (β = 1.9, p = 0.0013), and significant correlation between lateral supine ratio polysomnography 1 and lateral supine ratio polysomnography 2 (β = 0.95, p < 0.001) indicated strong consistency in sleep preference. Overall, the findings suggest that some individuals have low tolerance to supine posture, represented by a comparatively high wake index in the supine position, and that these individuals compensate by sleeping a greater proportion in the lateral position., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The aims of this study were (1) to determine how stair-climbing-based exercise snacks (ES) compared to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness (CRF), and (2) to explore whether ES could improve maximal fat oxidation rate (MFO) in inactive adults. Healthy, young, inactive adults ( n : 42, age: 21.6 ± 2.3 years, BMI: 22.5 ± 3.6 kg·m -2 , peak oxygen uptake (VO 2 peak): 33.6 ± 6.3 mL·kg -1 ·min -1 ) were randomly assigned to ES, MICT, or Control. ES ( n  = 14) and MICT ( n  = 13) groups performed three sessions per week over 6 weeks, while the control group ( n  = 15) maintained their habitual lifestyle. ES involved 3 × 30 s "all-out" stair-climbing (6 flight, 126 steps, and 18.9 m total height) bouts separated by >1 h rest, and MICT involved 40 min × 60%-70% HR max stationary cycling. A significant group × time interaction was found for relative VO 2 peak ( p  < 0.05) with ES significantly increasing by 7% compared to baseline (MD = 2.5 mL·kg -1 ·min -1 (95% CI = 1.2, 3.7), Cohen's d  = 0.44), while MICT had no significant effects (MD = 1.0 mL·kg -1 ·min -1 (-1.1, 3.2), Cohen's d  = 0.17), and Control experienced a significant decrease (MD = -1.7 mL·kg -1 ·min -1 (-2.9, -0.4), Cohen's d  = 0.26). MFO was unchanged among the three groups (group × time interaction, p  > 0.05 for all). Stair climbing-based ES are a time-efficient alternative to MICT for improving CRF among inactive adults, but the tested ES intervention appears to have limited potential to increase MFO., Competing Interests: No conflicts and interests are relevant to the content of this research.

Aims/hypothesis: The aim of the present study was to conduct a randomised, placebo-controlled, double-blind, crossover trial to determine whether pre-meal ketone monoester ingestion reduces postprandial glucose concentrations in individuals with type 2 diabetes., Methods: In this double-blind, placebo-controlled, crossover design study, ten participants with type 2 diabetes (age 59±1.7 years, 50% female, BMI 32±1 kg/m 2 , HbA 1c 54±2 mmol/mol [7.1±0.2%]) were randomised using computer-generated random numbers. The study took place at the Nutritional Physiology Research Unit, University of Exeter, Exeter, UK. Using a dual-glucose tracer approach, we assessed glucose kinetics after the ingestion of a 0.5 g/kg body mass ketone monoester (KME) or a taste-matched non-caloric placebo before a mixed-meal tolerance test. The primary outcome measure was endogenous glucose production. Secondary outcome measures were total glucose appearance rate and exogenous glucose appearance rate, glucose disappearance rate, blood glucose, serum insulin, β-OHB and NEFA levels, and energy expenditure., Results: Data for all ten participants were analysed. KME ingestion increased mean ± SEM plasma beta-hydroxybutyrate from 0.3±0.03 mmol/l to a peak of 4.3±1.2 mmol/l while reducing 2 h postprandial glucose concentrations by ~18% and 4 h postprandial glucose concentrations by ~12%, predominately as a result of a 28% decrease in the 2 h rate of glucose appearance following meal ingestion (all p<0.05). The reduction in blood glucose concentrations was associated with suppressed plasma NEFA concentrations after KME ingestion, with no difference in plasma insulin concentrations between the control and KME conditions. Postprandial endogenous glucose production was unaffected by KME ingestion (mean ± SEM 0.76±0.15 and 0.88±0.10 mg kg -1 min -1 for the control and KME, respectively). No adverse effects of KME ingestion were observed., Conclusions/interpretation: KME ingestion appears to delay glucose absorption in adults with type 2 diabetes, thereby reducing postprandial glucose concentrations. Future work to explore the therapeutic potential of KME supplementation in type 2 diabetes is warranted., Trial Registration: ClinicalTrials.gov NCT05518448., Funding: This project was supported by a Canadian Institutes of Health Research (CIHR) Project Grant (PJT-169116) and a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (RGPIN-2019-05204) awarded to JPL and an Exeter-UBCO Sports Health Science Fund Project Grant awarded to FBS and JPL., (© 2024. The Author(s).)

The aim of this study was to design physics-preserving and precise surrogate models of the nonlinear elastic behaviour of an intervertebral disc (IVD). Based on artificial force-displacement data sets from detailed finite element (FE) disc models, we used greedy kernel and polynomial approximations of second, third and fourth order to train surrogate models for the scalar force-torque -potential. Doing so, the resulting models of the elastic IVD responses ensured the conservation of mechanical energy through their structure. At the same time, they were capable of predicting disc forces in a physiological range of motion and for the coupling of all six degrees of freedom of an intervertebral joint. The performance of all surrogate models for a subject-specific L4 | 5 disc geometry was evaluated both on training and test data obtained from uncoupled (one-dimensional), weakly coupled (two-dimensional), and random movement trajectories in the entire six-dimensional (6d) physiological displacement range, as well as on synthetic kinematic data. We observed highest precisions for the kernel surrogate followed by the fourth-order polynomial model. Both clearly outperformed the second-order polynomial model which is equivalent to the commonly used stiffness matrix in neuro-musculoskeletal simulations. Hence, the proposed model architectures have the potential to improve the accuracy and, therewith, validity of load predictions in neuro-musculoskeletal spine models., (© 2024. The Author(s).)

Background: Substantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes., Methods: We conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR: <50 g carbohydrates; ~850-1100 kcal/day; n = 20) versus treatment-as-usual (TAU; n = 16). Participants were people with T2D, using ≥ 1 glucose-lowering medication, and a body mass index of ≥ 30 kg/m 2 . Main outcomes were C-peptide to proinsulin ratio, circulating microRNA 375 (miR375), homeostatic model assessment (HOMA) beta-cell function (B), fatty liver index (FLI), hepatic steatosis index (HSI), HOMA insulin resistance (IR), and circulating fetuin-A and fibroblast growth factor 21 (FGF21). Data were analysed using linear regression with baseline as a covariate., Results: There was no observed change in miR375 (p = 0.42), C-peptide to proinsulin ratio (p = 0.17) or HOMA B (p = 0.15). FLI and HSI were reduced by -25.1 (p < 0.0001) and - 4.9 (p < 0.0001), respectively. HOMA IR was reduced by -46.5% (p = 0.011). FGF21 was reduced by -161.2pg/mL (p = 0.035) with a similar tendency found for fetuin-A (mean difference: -16.7ng/mL; p = 0.11). These improvements in markers of hepatic function were accompanied by reductions in circulating metabolites linked to hepatic insulin resistance (e.g., diacylglycerols, ceramides) in the Pharm TCR group., Conclusions: The Pharm-TCR intervention did not improve fasting indices of beta-cell stress; however, markers of liver fat accumulation and and liver function were improved, suggesting that a LCER diet can improve some aspects of the underlying pathophysiology of T2D., Trial Registration: Clinicaltrials.gov (NCT03181165)., (© 2024. The Author(s).)

Two high-intensity interval training (HIIT) regimens are often used in research and clinical settings. Yet, there has been no direct comparison to determine if one can improve glucose control and variability to a greater extent in individuals living with type 2 diabetes (T2D). Fourteen older females with T2D participated in a semi-randomized control trial where HIIT10 (10 × 1-min intervals at 90% heart rate max; HRmax) and HIIT4 (4 × 4-min intervals at 90% of HRmax) were compared to a control condition (CON; no exercise). Continuous glucose monitoring was used to assess glucose control and variability over 24 h after each condition. Both HIIT10 (-2.1 ± 1.1 mmol/L) and HIIT4 (-2.1 ± 1.3 mmol/L) acutely lowered glucose compared to CON (-0.7 ± 0.8 mmol/L; p  = 0.001), with no difference between exercise conditions. This glucose-lowering effect did not persist over the 24-h post-exercise period, as both mean glucose ( p  = 0.751) and glucose variability ( p  = 0.168) were not significantly different among conditions. However, exploratory analyses focusing on individuals with less optimal glucose control (above median 24-h mean glucose in the CON condition; n  = 7) revealed that 24-h mean glucose (7.4 [7.14-8.92] vs. 8.4 [7.5-9.9] mmol/L; p  = 0.048), glucose variability ( p  = 0.010), and peak glucose ( p  = 0.048) were lower following HIIT10 compared to CON, while HIIT4 reduced time spent in moderate hyperglycemia compared to CON ( p  = 0.023). Both HIIT10 and HIIT4 acutely lower glycemia, but the effect does not persist over 24 h. However, in individuals with worse glucose control, HIIT10 may improve mean 24-h glucose and glycemic variability, while HIIT4 may reduce time spent in moderate hyperglycemia., Competing Interests: The authors declare no conflict of interest.

Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1). Next (Study 2), we investigated if exogenously raising BHB acutely in vivo by ketone monoester supplementation (KME) in adults with T2D would suppress pro-inflammatory plasma cytokines. In Study 3, we investigated the effect of BHB on inflammation via ex vivo treatment of LPS-stimulated leukocytes with BHB and in vivo thrice-daily pre-meal KME for 14 days in adults with T2D. Ex vivo treatment with BHB suppressed LPS-stimulated IL-1β, TNF-α, and IL-6 secretion and increased IL-1RA and IL-10 (Study 1). Plasma IL-10 increased by 90 min following ingestion of a single dose of KME in T2D, which corresponded to peak blood BHB (Study 2). Finally, 14 days of thrice-daily KME ingestion did not significantly alter plasma cytokines or leukocyte subsets including monocyte and T-cell polarization (Study 3). However, direct treatment of leukocytes with BHB modulated TNF-α, IL-1β, IFN-γ, and MCP-1 secretion in a time- and glucose-dependent manner (Study 3). Therefore, BHB appears to be anti-inflammatory in T2D, but this effect is transient and is modulated by the presence of disease, glycaemia, and exposure time., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The present meta-analysis aimed to assess the effects of low-volume high-intensity interval training (LV-HIIT; i.e., ≤5 min high-intensity exercise within a ≤15 min session) on cardiometabolic health and body composition. A systematic search was performed in accordance with PRISMA guidelines to assess the effect of LV-HIIT on cardiometabolic health and body composition. Twenty-one studies (moderate to high quality) with a total of 849 participants were included in this meta-analysis. LV-HIIT increased cardiorespiratory fitness (CRF, SMD = 1.19 [0.87, 1.50]) while lowering systolic blood pressure (SMD = -1.44 [-1.68, -1.20]), diastolic blood pressure (SMD = -1.51 [-1.75, -1.27]), mean arterial pressure (SMD = -1.55 [-1.80, -1.30]), MetS z-score (SMD = -0.76 [-1.02, -0.49]), fat mass (kg) (SMD = -0.22 [-0.44, 0.00]), fat mass (%) (SMD = -0.22 [-0.41, -0.02]), and waist circumference (SMD = -0.53 [-0.75, -0.31]) compared to untrained control (CONTROL). Despite a total time-commitment of LV-HIIT of only 14%-47% and 45%-94% compared to moderate-intensity continuous training and HV-HIIT, respectively, there were no statistically significant differences observed for any outcomes in comparisons between LV-HIIT and moderate-intensity continuous training (MICT) or high-volume HIIT. Significant inverse dose-responses were observed between the change in CRF with LV-HIIT and sprint repetitions ( β = -0.52 [-0.76, -0.28]), high-intensity duration ( β = -0.21 [-0.39, -0.02]), and total duration ( β = -0.19 [-0.36, -0.02]), while higher intensity significantly improved CRF gains. LV-HIIT can improve cardiometabolic health and body composition and represent a time-efficient alternative to MICT and HV-HIIT. Performing LV-HIIT at a higher intensity drives higher CRF gains. More repetitions, longer time at high intensity, and total session duration did not augment gains in CRF., Competing Interests: No conflicts and interests are relevant to the content of this review.

Purpose: To understand how the axial plane deformity contributes to progression of the three-dimensional spinal deformity of Adolescent Idiopathic Scoliosis (AIS), with a main thoracic curve type, using a series of sequential magnetic resonance images (MRI)., Methods: Twenty-seven AIS patients (at scan 1: mean 12.4 years (± 1.5), mean Cobb angle 29.1°(± 8.8°)) had 3 MRI scans (T4-L1) performed at intervals of mean 0.7 years (± 0.4). The outer profile of the superior and inferior endplates were traced on a reformatted axial image using ImageJ (NIH). Endplate AVR, and intravertebral rotation (IVR), defined as the difference between superior and inferior endplate AVR, was calculated for each vertebral level., Results: For all patients and scans, the mean AVR was greatest at the curve apex, with AVR diminishing in a caudal and cephalic direction from the apex. At scan 3 the mean apical AVR was 15.1°(± 4.6°) with a mean change in apical AVR between MRI 1 and 3 of 2.7°(± 2.9°). The increase in standing height between MRI 1 and 3 was mean 7.4 cm (± 4.6). Linear regression showed a positive correlation between apical AVR and Cobb angle (R 2  = 0.57, P < 0.001), and a positive correlation between apical AVR and rib hump (R 2  = 0.54, p < 0.001). The mean change in IVR was greater 3 vertebral levels cephalic and caudal to the apex (1.4°(± 4.1°) and 1.2°(± 2.0°), respectively), compared to the apex (0.4°(± 3.1°))., Conclusions: AVR increased, during curve progression, most markedly at the curve apex. The greatest IVR was observed at the periapical levels, with the apex by contrast having only a modest degree of rotation, suggesting the periapical vertebral levels of the scoliosis deformity may be a significant driver in the progression of AIS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Overactivation of the NLRP3 inflammasome is implicated in chronic low-grade inflammation associated with various disease states, including obesity, type 2 diabetes, atherosclerosis, Alzheimer's disease, and Parkinson's disease. Emerging evidence, mostly from cell and animal models of disease, supports a role for ketosis in general, and the main circulating ketone body beta-hydroxybutyrate (BHB) in particular, in reducing NLRP3 inflammasome activation to improve chronic inflammation. As a result, interventions that can induce ketosis (e.g., fasting, intermittent fasting, time-restricted feeding/eating, very low-carbohydrate high-fat ketogenic diets) and/or increase circulating BHB (e.g., exogenous ketone supplementation) have garnered increasing interest for their therapeutic potential. The purpose of the present review is to summarize our current understanding of the literature on how ketogenic interventions impact the NLRP3 inflammasome across human, rodent and cell models. Overall, there is convincing evidence that ketogenic interventions, likely acting through multiple interacting mechanisms in a cell-, disease- and context-specific manner, can reduce NLRP3 inflammasome activation. The evidence supports a direct effect of BHB, although it is important to consider the myriad of other metabolic responses to fasting or ketogenic diet interventions (e.g., elevated lipolysis, low insulin, stable glucose, negative energy balance) that may also impact innate immune responses. Future research is needed to translate promising findings from discovery science to clinical application., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

In the workplace, people are often sedentary for prolonged time and do not regularly engage in physical activity-two factors independently linked to premature morbidity and mortality. This study aimed to determine the receptivity of incorporating practical stair-climbing "exercise snacks" (Snacks; three isolated bouts of ascending 53-60 stairs performed sporadically throughout the day) into workplace settings compared to more traditional high-intensity interval training (HIIT; performed as three bouts of 53-60 stairs within a structured HIIT workout) and to explore if these exercise strategies could influence sedentary and physical activity behaviour. Fourteen participants (12 women; M age = 38.9 ± 10.2 years) completed two supervised exercise trials (Snacks and HIIT) followed by 1 week participating in either form of exercise in their workplace. Ratings of perceived exertion (RPE), affective valence, enjoyment, and self-efficacy were measured at the supervised exercise sessions. During the follow-up period, sedentary behaviour and physical activity were measured with an accelerometer. Affective valence was more positive ( p  = 0.03; η 2 p  = 0.21) and there was a lower rise in RPE ( p  = 0.01; η 2 p  = 0.29) during Snacks than HIIT. Post-exercise enjoyment of, and self-efficacy towards, Snacks and HIIT were high and similar ( p s > 0.05). After the supervised trials, 10/14 of the participants preferred Snacks and 4/14 preferred HIIT ( p  = 0.18). On days when participants chose to perform either exercise modality, the average number of sit-to-stands in a 24 h period was increased (48.3 ± 8.7 to 52.8 ± 7.8; p  = 0.03; Hedge's g  = 0.73) and moderate-to-vigorous physical activity tended to increase (21.9 ± 18.2 to 38.1 ± 22.1 min; p  = 0.06; Hedge's g  = 0.60) compared to days when they chose not to exercise. Stair-climbing exercise snacks may be an attractive approach to implement in the workplace setting and has potential to positively impact sedentary behaviour and physical activity metrics., Competing Interests: The authors declare there are no competing interests. MJS is currently a full-time employee (Senior Research Scientist) at Lululemon. This study was completed while he was a postdoctoral fellow at the University of British Columbia, before starting his role at Lululemon, and is unrelated to his current work. MJS has not received (or will receive) any compensation from Lululemon towards this study or completion of this manuscript.

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1 ) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2 ) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood β-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted. NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.

Exogenous ketone monoesters can raise blood β-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood β-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-β-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood β-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. β-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve ( p  < 0.05) and peak β-OHB ( p   < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-β-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised β-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.

Exogenous ketone supplements have been suggested to have potential cardiovascular benefits, but their overall effect on blood pressure is unclear. Our objective was to perform a systematic review and meta-analysis on the effects of exogenous ketone supplements on blood pressure (BP) and concomitant changes in resting heart rate (HR). Five databases were searched on January 27 th , 2023, for randomized and non-randomized studies. A random-effects model meta-analysis was performed including all studies jointly and separately for acute and chronic ingestion of ketone supplements. Out of 4012 studies identified in the search, 4 acute and 6 chronic studies with n  = 187 participants were included. Pooled results ( n  = 10) showed no change in systolic (SMD [95% CI]= -0.14 [-0.40; 0.11]; I 2 = 30%; p  = 0.17) or diastolic BP (-0.12 [-0.30; 0.05]; I 2 = 0%; p  = 0.69), with a potential tendency observed toward increased resting heart rate (0.17 [-0.14; 0.47]; I 2 = 40%; p  = 0.10). Similar results for systolic and diastolic BP were observed when assessing separately the effect of acute and chronic ingestion of ketone supplements ( p  ≥ 0.33). Supplement dosage was found to modulate the increase in resting heart rate (0.019 ± 0.006; p  = 0.013; R 2 =100%), suggesting that higher supplement doses lead to a higher resting heart rate. Based on currently available data, acute or prolonged ingestion of ketone supplements does not seem to modulate BP. However, a tendency for HR to increase after acute ingestion was observed, particularly with higher doses. Higher quality studies with appropriate standardized measurements are needed to confirm these results.

Study Design: This is a case-control study of prospectively collected data., Objective: To quantify paraspinal muscle size asymmetry in adolescent idiopathic scoliosis (AIS) and determine if this asymmetry is (i) greater than observed in adolescent controls with symmetrical spines; and (ii) positively associated with skeletal maturity using Risser grade, scoliosis severity using the Cobb angle, and chronological age in years., Summary of Background Data: AIS is a three-dimensional deformity of the spine which occurs in 2.5% to 3.7% of the Australian population. There is some evidence of asymmetry in paraspinal muscle activation and morphology in AIS. Asymmetric paraspinal muscle forces may facilitate asymmetric vertebral growth during adolescence., Methods: An asymmetry index [Ln(concave/convex volume)] of deep and superficial paraspinal muscle volumes, at the level of the major curve apex (Thoracic 8-9 th vertebral level) and lower-end vertebrae ( LEV , Thoracic 10-12 th vertebral level), was determined from three-dimensional Magnetic Resonance Imaging of 25 adolescents with AIS (all right thoracic curves), and 22 healthy controls (convex=left); all female, 10 to 16 years., Results: Asymmetry index of deep paraspinal muscle volumes was greater in AIS (0.16±0.20) than healthy spine controls (-0.06±0.13) at the level of the apex ( P <0.01, linear mixed-effects analysis) but not LEV ( P >0.05). Asymmetry index was positively correlated with Risser grade ( r =0.50, P <0.05) and scoliosis Cobb angle ( r =0.45, P <0.05), but not age ( r =0.34, P >0.05). There was no difference in the asymmetry index of superficial paraspinal muscle volumes between AIS and controls ( P >0.05)., Conclusions: The asymmetry of deep apical paraspinal muscle volume in AIS at the scoliosis apex is greater than that observed at equivalent vertebral levels in controls and may play a role in the pathogenesis of AIS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Interval training is a simple concept that refers to repeated bouts of relatively hard work interspersed with recovery periods of easier work or rest. The method has been used by high-level athletes for over a century to improve performance in endurance-type sports and events such as middle- and long-distance running. The concept of interval training to improve health, including in a rehabilitative context or when practiced by individuals who are relatively inactive or deconditioned, has also been advanced for decades. An important issue that affects the interpretation and application of interval training is the lack of standardized terminology. This particularly relates to the classification of intensity. There is no common definition of the term "high-intensity interval training" (HIIT) despite its widespread use. We contend that in a performance context, HIIT can be characterized as intermittent exercise bouts performed above the heavy-intensity domain. This categorization of HIIT is primarily encompassed by the severe-intensity domain. It is demarcated by indicators that principally include the critical power or critical speed, or other indices, including the second lactate threshold, maximal lactate steady state, or lactate turnpoint. In a health context, we contend that HIIT can be characterized as intermittent exercise bouts performed above moderate intensity. This categorization of HIIT is primarily encompassed by the classification of vigorous intensity. It is demarcated by various indicators related to perceived exertion, oxygen uptake, or heart rate as defined in authoritative public health and exercise prescription guidelines. A particularly intense variant of HIIT commonly termed "sprint interval training" can be distinguished as repeated bouts performed with near-maximal to "all out" effort. This characterization coincides with the highest intensity classification identified in training zone models or exercise prescription guidelines, including the extreme-intensity domain, anaerobic speed reserve, or near-maximal to maximal intensity classification. HIIT is considered an essential training component for the enhancement of athletic performance, but the optimal intensity distribution and specific HIIT prescription for endurance athletes is unclear. HIIT is also a viable method to improve cardiorespiratory fitness and other health-related indices in people who are insufficiently active, including those with cardiometabolic diseases. Research is needed to clarify responses to different HIIT strategies using robust study designs that employ best practices. We offer a perspective on the topic of HIIT for performance and health, including a conceptual framework that builds on the work of others and outlines how the method can be defined and operationalized within each context., (© 2023. The Author(s).)

Study Design: A prospective cohort study., Objective: Detail typical three-dimensional segmental deformities and their rates of change that occur within developing adolescent idiopathic scoliosis (AIS) spines over multiple timepoints., Summary of Background Data: AIS is a potentially progressive deforming condition that occurs in three dimensions of the scoliotic spine during periods of growth. However, there remains a gap for multiple timepoint segmental deformity analysis in AIS cohorts during development., Materials and Methods: Thirty-six female patients with Lenke 1 AIS curves underwent two to six sequential magnetic resonance images. Scans were reformatted to produce images in orthogonal dimensions. Wedging angles and rotatory values were measured for segmental elements within the major curve. Two-tailed, paired t tests compared morphologic differences between sequential scans. Rates of change were calculated for variables given the actual time between successive scans. Pearson correlation coefficients were determined for multidimensional deformity measurements., Results: Vertebral bodies were typically coronally convexly wedged, locally lordotic, convexly axially rotated, and demonstrated evidence of local mechanical torsion. Between the first and final scans, apical measures of coronal wedging and axial rotation were all greater in both vertebral and intervertebral disk morphology than nonapical regions (all reaching differences where P <0.05). No measures of sagittal deformity demonstrated a statistically significant change between scans. Cross-planar correlations were predominantly apparent between coronal and axial planes, with sagittal plane parameters rarely correlating across dimensions. Rates of segmental deformity changes between earlier scans were characterized by coronal plane convex wedging and convexly directed axial rotation. The major locally lordotic deformity changes that did occur in the sagittal plane were static between scans., Conclusions: This novel investigation documented a three-dimensional characterization of segmental elements of the growing AIS spine and reported these changes across multiple timepoints. Segmental elements are typically deformed from initial presentation, and subsequent changes occur in separate orthogonal planes at unique times., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: With increasing global interest in sleep hygiene, sleep ergonomics is an area that has been largely understudied. During sleep individuals turn over during the night to restore blood flow in occluded blood vessels, indicating that control of local tissue pressure may play a role in improving sleep comfort. This study investigates the influence of mattress stiffness on tissue compressive stresses during supine lying., Methods: A subject-specific 3D finite element (FE) model of the pelvis area has been developed to simulate supine lying on substrates of varying firmness. Constitutive parameters for the adipose-skin tissue and muscle-organ tissue were calibrated using a novel application of the inverse finite element method., Findings: The compressive stress was consistently greatest in the muscle interfacing the sacrum at 18.5 kPa on the soft foam, and 30.9 kPa on the firm foam. From soft to firm, the compressive stress increased by 67% at the sacrum, 20% at the ischium, 42% at the lesser trochanter, and 50% at the skin., Interpretation: The non-linearity of the foam substrate had a pressure distributing effect, relieving the peak compressive stresses at the sacrum, indicating that it may be possible to design arrays of foam substrates that can provide most efficient pressure relief., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Vertebral body tethering (VBT) is a recent procedure to correct and reduce spinal curves in skeletally immature patients with adolescent idiopathic scoliosis (AIS). The purpose of this systematic review and meta-analysis is to determine the expected curve reduction and potential complications for adolescent patients after VBT., Methods: PubMed, Embase, Google Scholar and Cochrane databases were searched until February 2022. Records were screened against pre-defined inclusion and exclusion criteria. Data sources were prospective and retrospective studies. Demographics, mean differences in Cobb angle, surgical details and complication rates were recorded. Meta-analysis was conducted using a random-effects model., Results: This systematic review includes 19 studies, and the meta-analysis includes 16 of these. VBT displayed a statistically significant reduction in Cobb angle from pre-operative to final (minimum 2 years) measurements. The initial mean Cobb angle was 47.8° (CI 95% 42.9-52.7°) and decreased to 22.2° (CI 95% 19.9-24.5°). The mean difference is - 25.8° (CI 95% - 28.9-22.7) (p < 0.01). The overall complication rate was 23% (CI 95% 14.4-31.6%), the most common complication was tether breakage 21.9% (CI 95% 10.6-33.1%). The spinal fusion rate was 7.2% (CI 95% 2.3-12.1%)., Conclusion: VBT results in a significant reduction of AIS at 2 years of follow-up. Overall complication rate was relatively high although the consequences of the complications are unknown. Further research is required to explore the reasons behind the complication rate and determine the optimal timing for the procedure. VBT remains a promising new procedure that is effective at reducing scoliotic curves and preventing spinal fusion in the majority of patients., Level of Evidence: Systematic review of Therapeutic Studies with evidence level II-IV., (© 2023. The Author(s).)

Background: In-task affective responses to moderate-intensity continuous exercise training (MICT) have been shown to predict future physical activity behavior. However, limited research has investigated whether this affect-behavior relationship is similar for high-intensity interval training (HIIT) and whether it holds true over the longer term. This study aims to determine (1) if in-task affect during 2 weeks of supervised MICT and HIIT predicted changes to unsupervised moderate-to-vigorous physical activity (MVPA) behavior 12 months post-intervention and (2) if this predictive relationship was moderated by exercise type (MICT vs. HIIT)., Method: Ninety-nine adults (69.7% female; 50.9 ± 9.4 years) who were low active and overweight were randomized to 2 weeks of exercise training of MICT (n = 52) or HIIT (n = 47), followed by 12 months of accelerometry-assessed free-living MVPA., Results: The pooled moderation model was not significant, F(3, 94) = 2.54, p = .07 (R 2  = 0.085), with a non-significant group by affect interaction (p = .06). The conditional effect for MICT was significant (B = 17.27, t = 2.17, p = .03), suggesting that 12-month change in MVPA increased by 17.27 min/week for every one-point increase in in-task affect. The conditional effect for HIIT was not significant (p = .85), suggesting that in-task affect was not predictive of 12-month change in MVPA., Conclusion: The current findings raise important questions about whether the affect-behavior relationship may vary depending on exercise type. For HIIT-based exercise in particular, additional psychological constructs beyond in-task affect should be considered when attempting to predict future physical activity behavior., (© 2023. International Society of Behavioral Medicine.)

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection., Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m 2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m 2 ; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated., Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE 2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8 + T cells (p adj = 0.014), whereas CD4 + T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients., Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Silva, Pereira, Minuzzi, Padilha, Figueiredo, Olean-Oliveira, dos Santos, von Ah Morano, Marchioto Júnior, Ribeiro, Dos Santos, Seelaender, Teixeira, Dos Santos, Lemos, Freire, Dorneles, Marmett, Olean-Oliveira, Teixeira, Seraphim, Caseiro, Pinho, Islam, Little, Krüger, Rosa-Neto, Coelho-E-Silva and Lira.)

Aims: Sarcopenia generally refers to the age-related reduction in muscle strength, functional ability, and muscle mass. Sarcopenia is a multifactorial condition associated with poor glucose disposal, insulin resistance, and subsequently type 2 diabetes (T2D). The pathophysiological connection between sarcopenia and T2D is complex but likely involves glycemic control, inflammation, oxidative stress, and adiposity., Methods and Results: Resistance exercise and aerobic training are two lifestyle interventions that may improve glycemic control in older adults with T2D and counteract sarcopenia. Further, there is evidence that dietary protein, Omega-3 fatty acids, creatine monohydrate, and Vitamin D hold potential to augment some of these benefits from exercise., Conclusions: The purpose of this narrative review is: (1) discuss the pathophysiological link between age-related sarcopenia and T2D, and (2) discuss lifestyle interventions involving physical activity and nutrition that may counteract sarcopenia and T2D., Competing Interests: Declaration of competing interest D.G.C. has conducted industry-sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. In addition, D.G.C. serves on the Scientific Advisory Board for Alzchem (a company that manufactures creatine) and as an expert witness/consultant in legal cases involving creatine supplementation., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Non-invasive monitoring of insulin could hold promise to identify those with, or at risk for developing, insulin resistance. We aimed to examine saliva insulin responses across the day following high- and low-carbohydrate meals and evaluate whether changes in saliva insulin might accurately reflect changes in plasma insulin. In two randomized crossover studies, young normal weight men (NW; n  = 8; Study 1) and adults with overweight/obesity (OO; n  = 8; Study 2) completed two 9-h experimental trials in which the participants consumed isocaloric mixed high-carbohydrate (HC) or low-carbohydrate (LC) meals at 0, 3, and 6 h. Plasma and saliva samples were collected at fasted baseline and every 30 min for a total of 19 samples across 9 h. Overall, findings revealed a similar trend for postprandial saliva and plasma insulin responses regardless of the time of the day with a ∼30-45 min lag between saliva and plasma insulin responses. In both NW and OO groups, saliva and plasma insulin area under the curve (AUC) and incremental AUC were significantly higher in HC condition as compared to LC condition (all P  ≤ 0.002). Nine-hour plasma and saliva insulin total AUCs were strongly and very strongly correlated in both HC ( r  = 0.68; P  = 0.007) and LC ( r  = 0.84, P  < 0.001) conditions, respectively. Saliva insulin is proportionate to and appears to reasonably track plasma insulin across the day with a ∼30-45 min delay. Saliva insulin shows promise as a non-invasive method to discern between low and high plasma insulin and may have utility in predicting the degree of insulin resistance (NCT03374436)., Competing Interests: JPL holds shares in Metabolic Insights Inc., a for-profit company that is developing non-invasive metabolic monitoring tools. HR, KO, and CRC declare that they have no conflicts of interest relevant to the content of this article.

Background: Effects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial., Objective: This study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects., Methods: Medline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression., Results: The meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = -0.3796, 95% CI [-0.4550, -0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30-60 min; >120 min) and insulin (30-60 min; 90-120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450-550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350-550 mg/kg)., Conclusion: Dose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication., Registry and Registry Number: PROSPERO (CRD42022360620)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In type 2 diabetes (T2D), consuming carbohydrates results in a rapid and large increase in blood glucose, particularly in the morning when glucose intolerance is highest., Objectives: We investigated if a low-carbohydrate (LC) breakfast (∼465 kcal: 25 g protein, 8 g carbohydrates, and 37 g fat) could improve glucose control in people with T2D when compared with a low-fat control (CTL) breakfast (∼450 kcal:20 g protein, 56 g carbohydrates, and 15 g fat)., Methods: Participants with T2D (N = 121, 53% women, mean age 64 y) completed a remote 3-month parallel-group randomized controlled trial comparing a LC with standard low-fat guideline CTL breakfast. The change in HbA1c was the prespecified primary outcome. Continuous glucose monitoring, self-reported anthropometrics, and dietary information were collected for an intention-to-treat analysis., Results: HbA1c was reduced (-0.3%; 95% CI: -0.4%, -0.1%) after 12 wks of a LC breakfast, but the between-group difference in HbA1c was of borderline statistical significance (-0.2; 95% CI: -0.4, 0.0; P = 0.06). Self-reported total daily energy (-242 kcal; 95% CI: -460, -24 kcal; P = 0.03) and carbohydrate (-73 g; 95% CI: -101, -44 g; P < 0.01) intake were lower in the LC group but the significance of this difference is unclear. Mean and maximum glucose, area under the curve, glycemic variability, standard deviation, and time above range were all significantly lower, and time in the range was significantly higher, in the LC group compared with CTL (all P < 0.05)., Conclusions: Advice and guidance to consume a LC breakfast appears to be a simple dietary strategy to reduce overall energy and carbohydrate intake and improve several continuous glucose monitoring variables when compared with a CTL breakfast in persons living with T2D. The trial was registered at clinicaltrials.gov as NCT04550468., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)