Regulation of metabolic health by dietary histidine in mice.

Low-protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched-chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. KEY POINTS: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in male mice. Reduced histidine does not extend the lifespan of mice when begun in midlife. Dietary levels of histidine are positively associated with body mass index in humans.

Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals.

Introduction: This study evaluated depression, monocyte phenotype, and immune function in physically active cannabis users. Methods: Participants (N = 23) were classified as either cannabis users (CU, n = 11) or non-users (NU, n = 12). White blood cells isolated from blood were analyzed for co-expression of cluster of differentiation 14 and 16 using flow cytometry. Lipopolysaccharide (LPS) was cultured with whole blood and assessed for interleukin-6 and tumor necrosis factor-α (TNF-α) release. Results: The percentage of white blood cells classified as monocytes was not different between groups; however, CU had a significantly greater percentage of monocytes classified as intermediate (p = 0.02). When standardized per milliliter of blood, CU had significantly greater numbers of total monocytes (p = 0.01), classical monocytes (p = 0.02), and intermediate monocytes (p = 0.01). Intermediate monocytes per milliliter of blood were positively correlated to the number of times CU used cannabis per day (r = 0.864, p < 0.01) and Beck Depression Inventory-II (BDI-II) score (r = 0.475, p = 0.03), which was significantly greater in CU (5.1 ± 4.8) compared with NU (0.8 ± 1.0; p < 0.01). CU released significantly less TNF-α per monocyte in response to LPS. Conclusions: CU had altered monocyte phenotypes and functions compared with NU. Elevations in intermediate monocytes were positively correlated with measures of cannabis use and BDI-II score.

Regular Use of Cannabis in Female Athletes Is Associated With a Reduction in Early Anaerobic Power Production.

ABSTRACT: Lisano, JK, Flores, VA, Kisiolek, JN, and Stewart, LK. Regular use of cannabis in female athletes is associated with a reduction in early anaerobic power production. J Strength Cond Res 37(3): 616-622, 2023-Despite a growing number of claims related to the ability of cannabis use to affect health and performance, there is limited research available, especially in female athletes. This cross-sectional study aimed to determine whether chronic cannabis use in physically active female athletes is related to altered health and performance. Healthy, physically active, female cannabis users (CU: n = 12) and noncannabis users (NU: n = 12) with an average age of 23.8 ± 3.7 years and 19.3 ± 4.2% body fat completed athletic performance and health assessments. Significance was set at alpha = 0.05. The age of onset of regular cannabis use was 20.1 ± 2.8 years in CU with an average duration of cannabis use of 5.8 ± 3.1 years. There were no differences between groups with respect to body size, body composition, pulmonary function, cardiorespiratory function, or muscular strength. Cannabis users produced significantly less power in the first 2 stages of the Wingate assessment, but CU experienced significantly less anaerobic fatigue. Although body composition and cardiovascular fitness were comparable, average C-reactive protein concentration classified CU with higher risk for cardiovascular disease (CVD). Athletes and coaches who rely heavily on anaerobic performance should consider these findings because they indicate that regular cannabis use may affect early power production and CVD risk.

Knee Kinetics During Squats of Varying Loads and Depths in Recreationally Trained Women.

Flores, V, Becker, J, Burkhardt, E, and Cotter, J. Knee kinetics during squats of varying loads and depths in recreationally trained women. J Strength Cond Res 34(7): 1945-1952, 2020-The back squat exercise is typically practiced with varying squat depths and barbell loads. However, depth has been inconsistently defined, resulting in unclear safety precautions when squatting with loads. In addition, women exhibit anatomical and kinematic differences to men, which may predispose them to knee joint injuries. The purpose of this study was to characterize peak knee extensor moments (pKEMs) at 3 commonly practiced squat depths of above-parallel, parallel, and full depths, and with 3 loads of 0 (unloaded), 50, and 85% depth-specific 1 repetition maximum (1RM) in recreationally active women. Nineteen women (age, 25.1 ± 5.8 years; body mass, 62.5 ± 10.2 kg; height, 1.6 ± 0.10 m; mean ± SD) performed squats of randomized depth and load. Inverse dynamics were used to obtain pKEMs from 3-dimensional knee kinematics. Depth and load had significant interaction effects on pKEMs (p = 0.014). Significantly greater pKEMs were observed at full depth compared with parallel depth with 50% 1RM load (p = 0.001, d = 0.615) and 85% 1RM load (p = 0.010, d = 0.714). Greater pKEMs were also observed at full depth compared with above-parallel depth with 50% 1RM load (p = 0.003, d = 0.504). Results indicate that effect of load on female pKEMs do not follow a progressively increasing pattern with either increasing depth or load. Therefore, when high knee loading is a concern, individuals must carefully consider both the depth of squat being performed and the relative load they are using.

A Casino goes smoke free: a longitudinal study of secondhand and thirdhand smoke pollution and exposure.

BACKGROUND: Secondhand smoke (SHS) in US casinos is common, but little is known about the residue of tobacco smoke pollutants left behind in dust and on surfaces, commonly referred to as thirdhand smoke (THS). We examined SHS and THS pollution and exposure before and during a casino smoking ban and after smoking resumed. METHODS: A casino was visited nine times over a 15-month period to collect dust, surface and air samples in eight locations. Finger wipe and urine samples were collected from non-smoking confederates before and after a 4-hour casino visit. Samples were analysed for markers of SHS and THS pollution and exposure. RESULTS: Exceptionally high levels of THS were found in dust and on surfaces. Although the smoking ban led to immediate improvements in air quality, surface nicotine levels were unchanged and remained very high for the first month of the smoking ban. Surface nicotine decreased by 90% after 1 month (P<0.01), but nicotine and tobacco-specific nitrosamines in dust decreased more slowly, declining by 90% only after 3 months (P<0.01). Exposure was significantly reduced after the ban, but the benefits of the ban were reversed after smoking resumed. CONCLUSIONS: Long-term smoking in a casino creates deep THS reservoirs that persist for months after a smoking ban. A complete smoking ban immediately improves air quality and significantly reduces exposure to SHS and THS. However, THS reservoirs contribute to continued low-level exposure to toxicants. To accelerate the effect of smoking bans, remediation efforts should address specific THS reservoirs, which may require intensive cleaning as well as replacement of carpets, furniture and building materials.

Nurses' Communication of Safety Events to Nursing Home Residents and Families.

Although communication is an essential part of the nursing process, nurses have little to no formal education in how to best communicate patient safety event (PSE) information to nursing home (NH) residents and their family members. The current mixed-methods study tested an intervention aimed at educating nurses on how to communicate a PSE to residents/family members using a structured communication tool. Nurse participants improved their knowledge of PSE communication, especially about the cause of the event, what they would say to the resident/family member, and future prevention of the PSE. Through qualitative subgroup analysis, an increased number of empathic statements were noted post-intervention. The tool tested in this study provides structure to an important care process that is necessary for improving the culture of safety in NH settings. [Journal of Gerontological Nursing, 44(2), 25-32.].

Spatial release from simultaneous echo masking in bat sonar.

Big brown bats (Eptesicus fuscus) use biosonar to navigate and locate objects in their surroundings. During natural foraging, they often encounter echoes returned by a target of interest located to the front while other, often stronger, clutter echoes are returned from objects, such as vegetation, located to the sides or above. Nevertheless, bats behave as if they do not suffer interference from this clutter. Using a two-choice delay discrimination procedure, bats were tested for the masking effectiveness of clutter echoes on target echoes when the target echoes were delivered from the bat's front while clutter echoes were delivered from 90° overhead, a direction of lowpass filtering by the external ears. When clutter echoes are presented from the front at the same delay as target echoes, detection performance declines and clutter masking occurs. When the clutter echoes are presented at the same delay but from overhead, discrimination performance is unaffected and no masking occurs. Thus there is masking release for simultaneous off-axis lowpass clutter compared to masking by simultaneous clutter from the front. The bat's performance for simultaneous target and clutter echoes indicates a new role for the mechanism that separates overlapping echoes by decomposing the bat's auditory time-frequency representation.

Support moment distribution during the back squat at different depths and loads in recreationally trained females.

OBJECTIVES: The squat is used in athletic and clinical settings. However, the coordination of the lower extremity during the lift is not well understood. The purpose was to compare the peak moments of the lower extremity joints at three squat depths (above parallel, parallel and full) and three squat loads (unloaded, 50 % 1 repetition maximum, and 85 % of depth specific 1 repetition maximum) and find their contribution to support (Ms). DESIGN: Nineteen females performed squats in a randomized order. METHODS: Inverse dynamics and Winter's Ms equation were used to calculate peak moments of the hip, knee and ankle and calculate their contribution to Ms (α < 0.05). RESULTS: Peak hip and ankle extensor moments varied with load but not depth and were greatest when using 85 % 1 repetition maximum. Peak knee extensor moments demonstrated a depth by load interaction. Within each depth as load increased so too did peak knee extensor moments and were highest squatting below parallel when loaded. The hip and knee contribution to Ms demonstrated a depth by load interaction while the ankle was only influenced by load. Within each depth as load increased hip contribution increased whereas the knee decreased contribution. When squatting with load the contribution of the hip decreased at below parallel while the knee increased. CONCLUSIONS: To maximize peak hip moments squat with high load and to maximize peak knee moments squat deep with high load; however, depth and load dosages should be taken into consideration based on the status and goals of the individual.

Updated Systematic Review and Quantitative Synthesis of Physical Activity Levels in Multiple Sclerosis.

OBJECTIVE: This article provided an updated quantitative synthesis of physical activity levels in persons with multiple sclerosis compared with controls and other clinical populations. DESIGN: A systematic search through PubMed, Scopus, and PsycINFO was conducted for articles published between August 2016 and July 2022. Articles that included a group comparison of at least one measurement of physical activity between adults with multiple sclerosis and controls or other clinical populations were included in the meta-analysis. RESULTS: Twenty-four studies met the inclusion criteria and yielded a total of 119 comparisons. There was a moderate difference in physical activity levels between persons with multiple sclerosis and controls (effect size = -0.56, P < 0.01), but no significant difference between persons with multiple sclerosis and other clinical populations (effect size = 0.01, P = 0.90). The pooled effect sizes comparing multiple sclerosis with controls ( Q104 = 457.9, P < 0.01) as well as with clinical populations ( Q13 = 108.4, P < 0.01) were heterogeneous. Moderating variables included sex, disability status, measurement method, outcome, intensity, and application of a multiple sclerosis-specific cut-point. CONCLUSIONS: Physical activity levels remain significantly lower in persons with multiple sclerosis compared with controls, but the magnitude of difference has become smaller over the past decade. There is a need for continued development of effective physical activity programs that can reach the greater community with multiple sclerosis.

Diazepam nanocapsules as an alternative for sleep induction: Development study and toxicity assessment.

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models.

Dietary isoleucine content defines the metabolic and molecular response to a Western diet.

The amino acid composition of the diet has recently emerged as a critical regulator of metabolic health. Consumption of the branched-chain amino acid isoleucine is positively correlated with body mass index in humans, and reducing dietary levels of isoleucine rapidly improves the metabolic health of diet-induced obese male C57BL/6J mice. However, it is unknown how sex, strain, and dietary isoleucine intake may interact to impact the response to a Western Diet (WD). Here, we find that although the magnitude of the effect varies by sex and strain, reducing dietary levels of isoleucine protects C57BL/6J and DBA/2J mice of both sexes from the deleterious metabolic effects of a WD, while increasing dietary levels of isoleucine impairs aspects of metabolic health. Despite broadly positive responses across all sexes and strains to reduced isoleucine, the molecular response of each sex and strain is highly distinctive. Using a multi-omics approach, we identify a core sex- and strain- independent molecular response to dietary isoleucine, and identify mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype. Intriguingly, the metabolic effects of reduced isoleucine in mice are not associated with FGF21 - and we find that in humans plasma FGF21 levels are likewise not associated with dietary levels of isoleucine. Finally, we find that foods contain a range of isoleucine levels, and that consumption of dietary isoleucine is lower in humans with healthy eating habits. Our results demonstrate that the dietary level of isoleucine is critical in the metabolic and molecular response to a WD, and suggest that lowering dietary levels of isoleucine may be an innovative and translatable strategy to protect from the negative metabolic consequences of a WD.

When to approach novel prey cues? Social learning strategies in frog-eating bats.

Animals can use different sources of information when making decisions. Foraging animals often have access to both self-acquired and socially acquired information about prey. The fringe-lipped bat, Trachops cirrhosus, hunts frogs by approaching the calls that frogs produce to attract mates. We examined how the reliability of self-acquired prey cues affects social learning of novel prey cues. We trained bats to associate an artificial acoustic cue (mobile phone ringtone) with food rewards. Bats were assigned to treatments in which the trained cue was either an unreliable indicator of reward (rewarded 50% of the presentations) or a reliable indicator (rewarded 100% of the presentations), and they were exposed to a conspecific tutor foraging on a reliable (rewarded 100%) novel cue or to the novel cue with no tutor. Bats whose trained cue was unreliable and who had a tutor were significantly more likely to preferentially approach the novel cue when compared with bats whose trained cue was reliable, and to bats that had no tutor. Reliability of self-acquired prey cues therefore affects social learning of novel prey cues by frog-eating bats. Examining when animals use social information to learn about novel prey is key to understanding the social transmission of foraging innovations.

Genome-wide tracing to decipher nuclear organization.

Nuclear organization impacts gene expression activity and cell phenotype. Our current understanding is mainly derived from ensemble-level sequencing studies that reflect the 3D genome structure of millions of cells. These approaches have provided invaluable details on the 3D organizations of the genome and their relation to other nuclear landmarks. However, they mostly lack the ability to provide multimodal information simultaneously at the single-cell level. In recent years, cutting-edge imaging technologies have risen to the challenge of simultaneously describing multiple components of the nuclear space at the single-cell level, paving the way for a deeper understanding of the genome structure-function relationship. This review will focus on the development and utilization of such technologies to gain a multi-component view of the nucleus at single-cell resolution, dissecting the complexity and heterogeneity of nuclear organization.

Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity.

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. METHODS: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. RESULTS: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). CONCLUSIONS: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.

Systematic review and meta-analysis of sedentary behavior in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups. METHODS: We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool). RESULTS: Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q16 = 72.2, p < 0.01; I2total = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool. CONCLUSIONS: The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.

Effects of aerobic, resistance, and combined exercise training on health-related quality of life in multiple sclerosis: Systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system that manifests in symptoms that compromise health-related quality of life (HRQOL). HRQOL focuses on a person's overall, subjective evaluation of health status primarily in the physical and mental domains. Exercise training is a form of rehabilitation for managing MS-related outcomes that might influence HRQOL. Reviews on exercise training are available, but we are unaware of a recent comprehensive review and meta-analysis of exercise effects for improving physical and mental domains of HRQOL. This analysis provides an updated review and meta-analysis of randomized controlled trials (RCTs) examining interventions consisting of aerobic, resistance and combined exercise training for improving HRQOL in persons with MS. This systematic review 1) assessed the overall strength of evidence for exercise interventions on HRQOL, 2) evaluated the relative effect of exercise interventions on physical and mental domains of HRQOL, and 3) determined moderators of exercise intervention effects on HRQOL. METHODS: Seven databases were searched for RCTs evaluating physical and/or mental domains of HRQOL with adults diagnosed with MS and undergoing an intervention of aerobic, resistance or combined exercise training compared with a non-exercise comparator. Data extraction included participant and intervention characteristics, and pre- and post-intervention HRQOL outcome data. Effect sizes (ESs) were calculated as standardized mean differences (SMDs) and a multilevel random-effects model was used to generate an aggregated SMD that compared exercise with non-exercise control conditions. RESULTS: Twelve RCTs met the inclusion criteria and yielded 23 ESs to be analyzed. Participants (N = 593; 308 intervention vs. 285 control conditions) had a mean (±standard deviation) age of 42.4 (6.5) years and 80% (18.3%) were female. Results generated a medium effect of exercise for improving overall HRQOL (ES=0.64, p = 0.0001) with high heterogeneity (Q11=58.8, I2=86.7%). Exercise training yielded a large effect on the physical domain (k = 12, ES=0.82, p<0.0009) and a medium effect on the mental domain (k = 11, ES=0.41, p<0.0001). Moderator analyses identified exercise modality, supervision level, intervention delivery and length, HRQOL tool, and number of participants with relapsing-remitting MS as significant influences of ES for HRQOL. CONCLUSIONS: Exercise training is clinically effective for improving overall HRQOL in MS and produces greater improvements in the physical domain of HRQOL than the mental domain. The moderator analysis suggests that supervised, aerobic, and group-delivered exercise training of ≥3 months yields the most influence on HRQOL. Such results may have major implications for MS treatment and care.

Targeted exercise for African-Americans with multiple sclerosis: Project TEAAMS.

BACKGROUND: We propose a randomized controlled trial (RCT) that examines the effects of a remotely-delivered, cultrally-tailored exercise training program for immediate and sustained improvements in patient-reported outcomes (PROs) of walking dysfunction, symptoms, and health-related quality of life (HRQOL) among African-Americans with multiple sclerosis (MS). METHODS/DESIGN: The study will be conducted using a parallel group RCT design. The RCT examines the effects of a remotely-delivered, culturally-tailored exercise training program compared with an active control condition among 100 African-Americans with MS. The primary PROs focus on walking dysfunction. The secondary PROs include symptoms of fatigue, depression, anxiety, and HRQOL. The tertiary PROs include exercise behavior and mediator variables based on social cognitive theory. Participants will be randomly assigned into one of two conditions, intervention (Aerobic and Resistance Exercise Training) or active control (Stretching and Flexibility), using a random numbers sequence with concealed allocation. The conditions will be administered over four months by a trained behavioral coach who will be uninvolved in recruitment, screening, random assignment, and outcome assessment. We will monitor the outcomes of interest before and after the 4-month intervention period, and then again 4 months after intervention cessation for capturing stability of intervention effects. The data analysis will follow intent-to-treat principles with a linear mixed model. DISCUSSION: If successful, this RCT will provide initial evidence for the uptake and implementation of the program in clinics/environments providing healthcare for African-Americans with MS.

Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial.

BACKGROUND: There is a lack of research on the effects of cannabidiol (CBD) on health-related fitness, physical activity, cognitive health, psychological wellbeing, and concentrations of C-reactive protein (CRP) in healthy individuals. CBD has potential anti-inflammatory and neuroprotective effects. METHODS: This study aimed to investigate the effects of 8 weeks of CBD on the above-mentioned measures in healthy individuals. Forty-eight participants were randomized into two groups receiving either oral capsules of 50 mg of CBD or a calorie-matched placebo daily. Participants completed pre- and post-intervention assessments, including blood draws, body composition, fitness, physical activity, and self-reported surveys. RESULTS: There were no significant differences between groups regarding body composition, aerobic fitness, muscular strength, physical activity, cognitive health, psychological wellbeing, and resting CRP concentrations. However, the placebo group experienced a decline in mean peak power and relative peak power compared to the CBD group. CONCLUSIONS: The results suggest that 8 weeks of CBD supplementation may prevent declines in anaerobic fitness over time. However, long-term CBD supplementation may not be beneficial for altering measures of health-related fitness, mental health, and inflammation in healthy individuals.

Particle motion is broadly represented in the vestibular medulla of the bullfrog across larval development.

In their shallow-water habitats, bullfrog (Rana catesbeiana) tadpoles are exposed to both underwater and airborne sources of acoustic stimulation. We probed the representation of underwater particle motion throughout the tadpole's dorsal medulla to determine its spatial extent over larval life. Using neurobiotin-filled micropipettes, we recorded neural activity to z-axis particle motion (frequencies of 40-200 Hz) in the medial vestibular nucleus, lateral vestibular nucleus, dorsal medullary nucleus (DMN), and along the dorsal arcuate pathway. Sensitivity was comparable in the medial and lateral vestibular nuclei, with estimated thresholds between 0.016 and 12.5 µm displacement. Neither best responding frequency nor estimated threshold varied significantly over larval stage. Transport of neurobiotin from active recording sites was also stable over development. The DMN responded poorly to z-axis particle motion, but did respond to low-frequency pressure stimulation. These data suggest that particle motion is represented widely and stably in the tadpole's vestibular medulla. This is in marked contrast to the representation of pressure stimulation in the auditory midbrain, where a transient "deaf period" of non-responsiveness and decreased connectivity occurs immediately prior to metamorphic climax. We suggest that, in bullfrogs, sensitivity to particle motion and to pressure follows different developmental trajectories.