Alaska Backcountry Expeditionary Hunting Promotes Sustained Muscle Protein Synthesis.

INTRODUCTION: We have previously described negative energy balance (ie, -9.7±3.4 MJ/d) and weight loss (Δ-1.5 ± 0.7 kg) influenced by high levels of energy expenditure (ie, 17.4±2.6 MJ/d) during remote expeditionary hunting in Alaska. Despite negative energy balance, participants retained skeletal muscle. The purpose of this pilot study was to measure skeletal muscle protein synthesis and examine molecular markers of skeletal muscle protein metabolism under similar conditions of physical and nutrient stress. METHODS: The "virtual biopsy method" was used to evaluate integrated fractional synthetic rates (FSRs) of muscle protein from blood samples in 4 participants. Muscle biopsies were taken to measure molecular markers of muscle protein kinetics (ie, FSTL1, MEF2, MYOD1, B2M, and miR-1-3p, -206, -208b, 23a, and 499a) using real-time polymerase chain reaction. RESULTS: Our findings in 4 participants (2 females [28 and 62 y of age; 66.2 and 71.8 kg body weight; 25.5 and 26.7 kg/m2 body mass index] and 2 males [47 and 56 y of age; 87.5 and 91.4 kg body weight; 26.1 and 28.3 kg/m2 body mass index]) describe mean muscle FSRs of serum carbonic anhydrase (2.4%) and creatine kinase M-type (4.0%) and positive increments in molecular regulation. CONCLUSIONS: Preservation of skeletal muscle under conditions of physical and nutrient stress seems to be supported by positive inflection of skeletal muscle FSR and molecular activation.

Alaska Mountain Wilderness Ski Classic: Alterations in Caloric Expenditure and Body Composition.

INTRODUCTION: The Alaska Mountain Wilderness Ski Classic is a self-supported ultramarathon cross-country skiing event that traverses one of the mountain ranges of Alaska each winter. Unique aspects of this event challenge athletes with a significant amount of physical and mental stress while in the chronically cold conditions of the Arctic. Assessment of energy requirements or body composition has never been performed during this event. The objective of the study was to evaluate the influence of the 2016 Alaska Mountain Wilderness Ski Classic on caloric expenditure and body composition. METHODS: Caloric expenditure was estimated using GT3x+ Actigraph accelerometers and ActiLife software. Lean tissue mass, total fat mass, visceral fat mass, and bone mineral density were measured using a General Electric iDXA before and after the event. Data are presented as mean±SD. Differences were analyzed using paired t tests with significance at P<0.05. RESULTS: Fifteen participants (age=32.7±6.6 years, body mass index=23.7±2.3 kg·m2) completed the study, 8 males and 7 females. Caloric expenditure was 6238±1390 kcal·day-1, and 37,163±8425 kcal for the entire event. Fat mass was reduced from pre-event (∆1.3±0.7 kg, P=0.00003). There was an increase in lean tissue mass (∆1.7±1.3 kg, P=0.0003) and relative skeletal muscle index (∆0.2±0.2 kg·m², P=0.001). There was no change in bone mineral density (∆0±0 g·cm3, P=0.4). CONCLUSIONS: Despite the metabolic demands, fat mass was reduced and lean tissue mass was preserved. Future studies of this event should be directed toward assessment of the nutritional provisions utilized and the mechanisms responsible for the preservation of lean tissue mass.

Contralesional Brain-Computer Interface Control of a Powered Exoskeleton for Motor Recovery in Chronic Stroke Survivors.

BACKGROUND AND PURPOSE: There are few effective therapies to achieve functional recovery from motor-related disabilities affecting the upper limb after stroke. This feasibility study tested whether a powered exoskeleton driven by a brain-computer interface (BCI), using neural activity from the unaffected cortical hemisphere, could affect motor recovery in chronic hemiparetic stroke survivors. This novel system was designed and configured for a home-based setting to test the feasibility of BCI-driven neurorehabilitation in outpatient environments. METHODS: Ten chronic hemiparetic stroke survivors with moderate-to-severe upper-limb motor impairment (mean Action Research Arm Test=13.4) used a powered exoskeleton that opened and closed the affected hand using spectral power from electroencephalographic signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. Patients used the system at home for 12 weeks. Motor function was evaluated before, during, and after the treatment. RESULTS: Across patients, our BCI-driven approach resulted in a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in BCI control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved. CONCLUSIONS: The findings demonstrate the therapeutic potential of a BCI-driven neurorehabilitation approach using the unaffected hemisphere in this uncontrolled sample of chronic stroke survivors. They also demonstrate that BCI-driven neurorehabilitation can be effectively delivered in the home environment, thus increasing the probability of future clinical translation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02552368.

Preliminary comparisons between a point-of-care ketometer and reference method using Steller sea lion pup whole blood and plasma.

We evaluated the Precision Xtra™ ketometer as part of a larger study categorizing fasting status of free-ranging Steller sea lion (Eumetopias jubatus; SSL) pups which necessitated the identification of plasma ß-hydroxybutyrate concentrations ([ß-HBA]) around a threshold of <0.3 and ≥0.3 mmol/l. Whole blood samples mixed with sodium heparin (NaHep) or ethylenediaminetetraacetic acid liquid anticoagulants were tested <10 minutes after collection (n = 14; triplicate technical replicates). Plasma (stored at -80°C, NaHep, Thaw1) measured via our laboratory's Reference Assay (Sigma Aldrich, St. Louis, MO, Kit #MAK041) served as the standard [ß-HBA] for ketometer comparisons. Our observed ß-HBA range (0.0-1.6 mmol/l), consistent with published [ß-HBA] of free-ranging Otariid pups, represented the lower 20% of the ketometer's range (0.0-8.0 mmol/l). The maximal coefficient of variation (%CV) of ketometer technical replicates was 9.1% (NaHep, whole blood). The majority of ketometer technical replicate sets (84%, including all matrices, anticoagulants and thawings) were identical (CV = 0%). We found linear relationships and agreement of ketometer [ß-HBA] between whole blood preserved with different anticoagulants and between whole blood and plasma (Thaw1) measurements. The ketometer produced results with linearity to the Reference Assay for both whole blood and plasma (Thaw1). We identified a non-linear relationship between plasma at Thaw1 and Thaw2 (tested four months apart, NaHep), as only samples with higher SSL [ß-HBA] decreased in concentration, and all others remained the same. With respect to categorizing SSL pup fasting in our larger study, the ketometer's %Accuracy, %Sensitivity and %Specificity for samples with Reference Assay ß-HBA <0.2 and >0.4 mmol/l were 100%. We adopted a modified procedure: plasma samples with mean ketometer concentrations ±0.1 mmol/l of 0.3 mmol/l ß-HBA were re-evaluated using the Reference Assay, improving measurement precision from tenths (ketometer) to thousandths (assay) mmol/l. The Precision Xtra™ ketometer was valuable to our application over the range of [ß-HBA] observed in SSL pup plasma and whole blood samples.

Physiology of the Wildland Firefighter: Managing Extreme Energy Demands in Hostile, Smoky, Mountainous Environments.

Wildland firefighters (WLFFs) are inserted as the front-line defense to minimize loss of natural resources, property, and human life when fires erupt in forested regions of the world. The WLFF occupation is physically demanding as exemplified by total daily energy expenditures that can exceed 25 MJ/day (6000 calories). WLFFs must also cope with complex physical and environmental situations (i.e., heat, altitude, smoke, compromised sleep, elevated stress) which challenge thermoregulatory responses, impair recovery, and increase short- and long-term injury/health risks while presenting logistical obstacles to nutrient and fluid replenishment. The occupation also imposes emotional strain on both the firefighter and their families. The long-term implications of wildfire management and suppression on the physical and mental health of WLFFs are significant, as the frequency and intensity of wildland fire outbreaks as well as the duration of the fire season is lengthening and expected to continue to expand over the next three decades. This article details the physical demands and emerging health concerns facing WLFFs, in addition to the challenges that the U.S. Forest Service and other international agencies must address to protect the health and performance of WLFFs and their ability to endure the strain of an increasingly dangerous work environment. © 2023 American Physiological Society. Compr Physiol 13:4587-4615, 2023.

Fasting durations of Steller sea lion pups vary among subpopulations-evidence from two plasma metabolites.

Geographic differences in population growth trends are well-documented in Steller sea lions (Eumetopias jubatus), a species of North Pacific pinniped listed under the U.S. Endangered Species Act in 1990 following a marked decline in population abundance that began during the 1970s. As population growth is intrinsically linked to pup production and survival, examining factors related to pup physiological condition provides useful information to management authorities regarding potential drivers of regional differences. During dam foraging trips, pups predictably transition among three fasting phases, distinguished by the changes in the predominant metabolic byproduct. We used standardized ranges of two plasma metabolites (blood urea nitrogen and ß-hydroxybutyrate) to assign pups to fasting categories (n = 1528, 1990-2016, 12 subpopulations): Recently Fed-Phase I (digestion/assimilation-expected hepatic/muscle glycogen usage), Phase II (expected lipid utilization), transitioning between Phases II-III (expected lipid utilization with increased protein reliance), or Phase III (expected protein catabolism). As anticipated, the majority of pups were classified as Recently Fed-Phase I (overall mean proportion = 0.72) and few pups as Phase III (overall mean proportion = 0.04). By further comparing pups in Short (Recently Fed-Phase II) and Long (all other pups) duration fasts, we identified three subpopulations with significantly (P < 0.03) greater proportions of pups dependent upon endogenous sources of energy for extended periods, during a life stage of somatic growth and development: the 1) central (0.27 ± 0.09) and 2) western (0.36 ± 0.13) Aleutian Island (declining population trend) and 3) southern Southeast Alaska (0.32 ± 0.06; increasing population trend) subpopulations had greater Long fast proportions than the eastern Aleutian Islands (0.10 ± 0.05; stabilized population). Due to contrasting population growth trends among these highlighted subpopulations over the past 50+ years, both density-independent and density-dependent factors likely influence the dam foraging trip duration, contributing to longer fasting durations for pups at some rookeries.

Bedrest and sarcopenia.

PURPOSE OF REVIEW: The primary focus of this review is to characterize the physiological elements of sarcopenia. In addition, we will also describe the impact of bedrest on sarcopenia and how various countermeasures may be able to offset the deleterious clinical consequences of unanticipated bedrest or hospitalization. It is well known that the aging process presents many challenges to the maintenance of overall health. With the increasing rate of obesity and the potentially simultaneous development of sarcopenia, bedrest presents a difficult clinical challenge to the elderly individual. RECENT FINDINGS: The etiology of accelerated sarcopenia has been described as a syndrome. The characteristics of this syndrome include combined alterations in neuromuscular control and muscle protein synthesis that increase the risk of morbidity and mortality in the elderly population. Moreover, the acute onset of bedrest-induced insulin resistance may further complicate the nutritionally derived maintenance of muscle mass and physical function. SUMMARY: Even though many questions remain unresolved concerning the optimal clinical management of elderly individuals who undergo unanticipated bedrest, the supplementation of essential amino acids has shown promise as a therapeutic strategy to minimize the detrimental influence of hospitalization in the elderly. In turn, this nutritional adjunctive therapy may reduce the length of stay and the likelihood of repeated hospitalization.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

BACKGROUND: Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. METHODS: In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. RESULTS: By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. CONCLUSION: The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Essential amino acid enriched meal replacement improves body composition and physical function in obese older adults: A randomized controlled trial.

BACKGROUND: Older adults are threatened by the risk of muscle atrophy and excess accumulation of adipose tissue. The objective of this study was to determine whether an essential amino acid enriched meal replacement would reduce excess fat and foster skeletal muscle retention, potentially improving physical function in this cohort. METHODS: Using a double blind, randomized controlled trial, we compared the influence of an experimental meal replacement enriched with essential amino acids (EMR) to a commercially available, widely used meal replacement (Optifast®) provided once/day (q.d.) for four weeks on body composition, skeletal muscle and physical function in obese older participants. Twenty-eight individuals completed either EMR (n = 13) or Optifast® (n = 15) supplementation protocols. Measurements of body composition, thigh skeletal muscle cross-sectional area (CSA), blood panels, intrahepatic lipid, and physical function were completed pre- and post-supplementation. RESULTS: Body fat mass, visceral fat mass and volume, and intrahepatic lipid were reduced with EMR but not with Optifast®. Thigh muscle CSA increased (Δ 2.4 ± 3.0 cm2) with EMR but not Optifast® (Δ -1.8 ± 6.0 cm2). There was a significant increase in the distance covered during the 6-min walk test with EMR (Δ 23 ± 27 m) but no change in Optifast® (Δ 11 ± 37 m). CONCLUSIONS: Beneficial alterations in fat and muscle support the use of EMR-based meal replacements in obese older adults. CLINICAL TRIAL REGISTRATION: ISRCTN registry under Reference Number ISRCTN15814848.

Deterioration of Lipid Metabolism Despite Fitness Improvements in Wildland Firefighters.

OBJECTIVE: Determine serum lipid and general health/fitness alterations following a 5-month wildfire suppression season. METHODS: We recruited 100 wildland firefighters (WLFFs) to a 5-month pre- to post-season observational study. Nude body mass, blood pressure (BP), grip strength, and steptest heart rate (HR) were recorded. Blood samples were collected for lipid panel analysis (total cholesterol, high density lipoproteins (HDL)-cholesterol, low density lipoproteins-cholesterol, very low density lipoproteinscholesterol, triglycerides, triglyceride:HDL-cholesterol ratio). Two-tailed dependent t tests determined statistical significance (P < 0.05). RESULTS: There were pre- to post-season changes in nude body mass (+2 ±â€Š4%, P  = 0.001), systolic BP (-2 ±â€Š10%, P  = 0.01), step-test HR (-5 ±â€Š10%, P  < 0.001), and all serum lipids (total cholesterol: +5 ±â€Š14%, P  = 0.02, HDL-cholesterol: = 1 ±â€Š17%, P  = 0.04, low density lipoproteins-cholesterol: +8 ±â€Š22%, P  = 0.02, very low density lipoproteins-cholesterol: +31 ±â€Š49%, P  < 0.001, triglycerides: +30 ±â€Š49%, P  < 0.001, triglyceride:HDL-cholesterol ratio: +37 ±â€Š58%, P  < 0.001). Pre- to post-season diastolic BP (P = 0.12) and grip strength (P = 0.60) remained stable. CONCLUSIONS: WLFFs demonstrate maladaptive serum lipids and body mass alterations despite subtle aerobic fitness improvements.

Planetary Protection Assessment of Radioisotope Thermoelectric Generator (RTG)-Powered Landed Missions to Ocean Worlds: Application to Enceladus.

Landed missions to icy worlds with a subsurface liquid water ocean must meet planetary protection requirements and ensure a sufficiently small likelihood of any microorganism-bearing part of the landed element reaching the ocean. A higher bound on this likelihood is set by the potential for radioisotope thermoelectric generator (RTG) power sources, the hottest possible landed element, to melt through the ice shell and reach the ocean. In this study, we quantify this potential as a function of three key parameters: surface temperature, ice shell thickness (i.e., heat flux through the shell), and thickness of a porous (insulating) snow or regolith cover. Although the model we describe can be applied to any ocean world, we present results in the context of a landed mission concept to the south polar terrain of Saturn's moon Enceladus. In this particular context, we discuss planetary protection considerations for landing site selection. The likelihood of forward microbial contamination of Enceladus' ocean by an RTG-powered landed mission can be made sufficiently low to not undermine compliance with the planetary protection policy.

Influences on glycocalyx shedding during the Yukon Arctic Ultra: the longest and the coldest ultramarathon.

The endothelial glycocalyx maintains vascular structure and may be subject to shedding during inflammation and also during high-intensive exercise. There are no studies on shedding during ultra-endurance exercise. The "Yukon Arctic Ultra" (YAU) is one of the longest and coldest ultramarathons and its impact on glycocalyx shedding was investigated. Thirteen adults (38.92 ± 8.67 yr, 6 females) of YAU editions 2015-2019 completed 657.03 ± 71.65 km at a moving velocity of 4.17 ± 0.62 km/h. Mean daily temperatures ranged from -12.6°C to -30.5°C. Glycocalyx elements heparan sulfate, hyaluronan, and syndecan CD-138 were quantified from serum at start, 277 km, 383 km, and 690 km. Cortisol, C-reactive protein, creatine kinase, and N-terminal-prohormone of brain natriuretic peptide were also quantified. Seven YAU volunteers (36.14 ± 11.04 yr, 5 females) served as control. There were no time-changes among the control. Among finishers, there was a significant increase for hyaluronan and a significant decrease for syndecan CD-138. Values were greater among female finishers for heparan sulfate at start, 383 km, and 690 km, and among male finishers for hyaluronan at 277 km. Values for syndecan CD-138 were greater among older finishers at all timepoints. There were weak significant correlations (R2 < 0.215) between hyaluronan and distance, creatine kinase, and NT-Pro BNP, respectively. Shedding of glycocalyx elements is shown among participants of the YAU. Greater shedding of heparan sulfate among female, greater increases of hyaluronan among male, and greater shedding of syndecan CD-138 among older athletes indicate complex glycocalyx shedding during ultra-endurance exercise.NEW & NOTEWORTHY This is the first study to investigate changes in glycocalyx elements in an endurance footrace and first study to investigate exercise-induced shedding in both sexes. This study comprised of an athlete group who finished the ultra-long distance of up to 690 km during the Yukon Arctic Ultra as well as a control group. Results indicate relevant and different shedding of glycocalyx elements heparan sulfate, hyaluronan, and syndecan CD-138. Sex, age, BMI, and covered distance appear to have an influence on the shedding. Other serum parameters indicative of stress appear to be associated with shedding.

Adiponectin, leptin, cortisol, neuropeptide Y and profile of mood states in athletes participating in an ultramarathon during winter: An observational study.

Background: The Montane® Yukon Arctic Ultra (YAU) is one of the longest (690 km) and coldest (+10.6°C-43.9°C) ultramarathons worldwide. Taking part in an ultramarathon is associated with great physiological and psychological stress, which can affect one's mood, level of hormones, and peptides. The current study aimed to identify relationships between peptides, hormones, and mood states in participants during this ultramarathon. Methods: The study cohort consisted of 36 participants (19 men, 17 women, 38.64 ± 9.12 years) split into a finisher (n = 10), non-finisher (n = 19), and control group (n = 7). Data were collected at four time points: baseline (PRE), during (D1 after 277 km, D2 after 383 km), and after the race (POST). Questionnaires were used to assess ratings of perceived exertion (RPE), total quality of recovery (TQR), and profile of mood states (POMS-SF). Serum NPY, leptin, adiponectin, and cortisol were measured. Results: Among non-finishers, scores for confusion, anger, depression, and tension-anxiety (PRE vs. D2, p < 0.05) increased, while vigor decreased (PRE vs. D1, p < 0.05). In contrast, finishers' tension-anxiety scores decreased (PRE vs. D1, p < 0.05). Fatigue increased in finishers (PRE vs. POST, p < 0.05) and non-finishers (PRE vs. D1, p < 0.05). In non-finishers, depressive mood correlated positively with leptin, anger, and confusion at several time points (p < 0.001). In finishers, NPY correlated with TQR at PRE (p < 0.05), while leptin correlated negatively with TQR at POST (p < 0.05). Tension-anxiety correlated highly with perceived exertion in non-finishers (p < 0.001) and with cortisol in finishers (p < 0.05) and non-finishers (p < 0.001). In finishers, confusion correlated negatively with NPY (p < 0.01). Conclusion: The study reveals an essential interplay between hormones and mood states affecting performance: Leptin was associated with anger and a depressive mood state in non-finishers and worse recovery in finishers. In contrast, NPY appeared linked to a lower confusion score and heightened recovery in finishers. A simultaneous increase in depressed mood, anger, tension-anxiety, and confusion might harm performance and lead to race failure.

Alaska backcountry expeditionary hunting promotes rapid improvements in metabolic biomarkers in healthy males and females.

We have previously reported negative energy balance and health benefits during an Alaska backcountry expeditionary hunting (ABEH) immersion in two males. The purpose of our present study was to increase the number of participants, include females, and evaluate macronutrient intake and serum lipids. Four men (age: 46 ± 6 year, BMI: 26 ± 1 kg/m2 ) and three women (age: 46 ± 11 year, BMI: 25 ± 3 kg/m2 ) were recruited. Doubly labeled water methodology and dietary recall were utilized to assess energy expenditure and energy intake, respectively. Data were collected during pre- and post-ABEH visits. Body composition was measured using dual-energy x-ray absorptiometry and the cross-sectional area of skeletal muscle in the upper leg (XT), and intrahepatic lipid (IHL) was determined using magnetic resonance imaging and/or spectroscopy (MRI/MRS). Blood parameters were measured by LabCorp. Paired T-tests were used for statistical analysis. Data are reported as mean ± SD and considered significant at p < 0.05. Total energy intake was 7.7 ± 3.4 MJ/day and total energy expenditure was 17.4 ± 2.6 MJ/day, resulting in a negative energy balance of -9.7 ± 3.4 MJ/day. Protein intake(grams)/body weight(kilograms)/day was 1.0 ± 0.4. There were reductions in body weight (Δ-1.5 ± 0.7 kg), BMI (Δ-0.3 ± 0.2 kg/m2 ), fat mass (Δ-1.7 ± 0.9 kg), and IHL (Δ-0.3 ± 0.3% water peak). There were no changes in lean tissue mass (Δ0.6 ± 1.4 kg) or XT (Δ-1.3 ± 3.3 cm2 ). There were significant reductions in total cholesterol (Δ-44 ± 35 mg/dl), LDL-cholesterol (Δ-25 ± 14 mg/dl), VLDL-cholesterol (Δ-7 ± 7 mg/dl), and triglycerides (Δ-35 ± 33 mg/dl). The ABEH immersion resulted in considerable negative energy balance and provided comprehensive benefits in metabolic health without any reduction in skeletal muscle.

Equivalent servings of free-range reindeer promote greater net protein balance compared to commercial beef.

Wild game consumption has been associated with health benefits but the acute influence on human protein metabolism remains unknown. We compared feeding-induced responses of equivalent amounts of free-range reindeer (FR) and commercial beef (CB) on protein kinetics using stable isotope methodology. Seven participants (age: 40 ± 14 years; body mass index: 24 ± 3 kg/m2) completed two randomised studies, ingesting 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole-body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via plasma sample isotope enrichment analysis by gas chromatography-mass spectrometry; plasma essential amino acid (EAA) concentrations were determined by liquid chromatography-electrospray ionisation-mass spectrometry. Plasma post-prandial EAA concentrations were higher with FR compared to CB (P < 0.05). The acute feeding-induced PS response was not different, but PB was reduced and contributed to a superior level of NB (P < 0.00001) in FR compared to CB. Our results demonstrate that FR may influence more favourable protein metabolism than CB. These data support potential health benefits of wild game onf whole-body protein.Abbreviations: BMI: body mass index; DIAAS: digestible indispensable amino acid score; CB: commercial beef; EAA: essential amino acids; FR: free-range reindeer; Ra: rate of appearance; UAF: University of Alaska Fairbanks; USDA: USA Department of Agriculture.

Nitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels.

Hibernation is a state of extraordinary metabolic plasticity. The pathways of amino acid metabolism as they relate to nitrogen homeostasis in hibernating mammals in vivo are unknown. Here we show, using pulse isotopic tracing, evidence of increased myofibrillar (skeletal muscle) protein breakdown and suppressed whole-body production of metabolites in vivo throughout deep torpor. As whole-body production of metabolites is suppressed, amino acids with nitrogenous side chains accumulate during torpor, while urea cycle intermediates do not. Using 15N stable isotope methodology in arctic ground squirrels (Urocitellus parryii), we provide evidence that free nitrogen is buffered and recycled into essential amino acids, non-essential amino acids and the gamma-glutamyl system during the inter-bout arousal period of hibernation. In the absence of nutrient intake or physical activity, our data illustrate the orchestration of metabolic pathways that sustain the provision of essential and non-essential amino acids and prevent ammonia toxicity during hibernation.

Feasibility of connecting regional research programs to national multisite trials emanating from the CTSA Trial Innovation Network.

A collaborative research model was developed and tested to enable regional healthcare systems to join multisite clinical trials emanating from the Clinical and Translational Science Award (CTSA) Trial Innovation Network (TIN) by the Institute of Translational Health Sciences at the University of Washington and the Northwest Participant and Clinical Interactions (NW PCI) Network. The NW PCI is a collaborative group of regional research programs located at medical centers, healthcare systems, and universities across Washington, Wyoming, Alaska, Montana, and Idaho. This article describes the purpose, development, barriers, and initial experience with feasibility assessment for TIN-supported studies in the NW PCI. The tools and processes of the NW PCI Network were adapted to enable network sites to assess studies for clinical relevance and feasibility. Seven of seventeen TIN-supported studies were reviewed for consideration; three of which resulted in successful completion of study documentation for site selection by NW PCI sites. The NW PCI/TIN model can be adapted by other CTSAs to increase involvement of regional research programs in national multisite clinical research studies. Barriers to expanding TIN-supported trials to regional networks include short timelines for study document submissions, insufficient site reimbursement rates, and non-feasible study designs.

Essential Amino Acid Supplement Lowers Intrahepatic Lipid despite Excess Alcohol Consumption.

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this exploratory pilot study was to initiate the evaluation of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38 ± 15 years/age and 7 females at 34 ± 18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 g of EAAS twice/day (BID)) or high dose (HD: 13 g of EAAS BID). Five of the twenty-five enrolled participants dropped out of the intervention. Both groups consumed the supplement BID for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual-energy X-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at p < 0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p = 0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407 ± 141 ng/mL and HD at 429 ± 196 ng/mL, indicating chronic and excess alcohol consumption. The HD of the proprietary EAAS formulation consumed BID seemed to lower IHL in individuals with mild to moderate AUD. We suggest that further studies in a larger cohort be conducted to more completely address this important area of investigation.

Prevention and treatment of type 2 diabetes: current role of lifestyle, natural product, and pharmacological interventions.

Common complications of type 2 diabetes (T2D) are eye, kidney and nerve diseases, as well as an increased risk for the development of cardiovascular disease and cancer. The overwhelming influence of these conditions contributes to a decreased quality of life and life span, as well as significant economic consequences. Although obesity once served as a surrogate marker for the risk of T2D, we know now that excess adipose tissue secretes inflammatory cytokines that left unchecked, accelerate the progression to insulin resistance and T2D. In addition, excess alcohol consumption may also increase the risk of T2D. From a therapeutic standpoint, lifestyle interventions such as dietary modification and/or exercise training have been shown to improve glucose homeostasis but may not normalize the disease process unless weight loss is achieved and increased physical activity patterns are established. Furthermore, utilization of natural products may serve as a significant adjunct in the fight against insulin resistance but further research is needed to ascertain their validity. Since it is clear that pharmaceutical therapy plays a significant role in the treatment of insulin resistance, this review will also discuss some of the newly developed pharmaceutical therapies that may work in conjunction with lifestyle interventions, and lessen the burden of behavioral change as the only strategy against the development of T2D.

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part A: recording.

OBJECTIVE: Advancement in prosthetic limb technology requires corresponding improvements in the capability of the amputee to naturally control the device via original motor pathways while simultaneously receiving haptic feedback via sensory pathways. Recording efferent axonal activity using a peripheral neural interface (PNI) allows a good tradeoff between invasiveness and selectivity while possibly preserving the phenomenology of controlling the original limb. One such PNI, the thin-film transverse intrafascicular multichannel electrode (tfTIME), has been shown to be successful in controlling powered prosthetics. However, the tfTIME is highly susceptible to stimulation artifact; thus, using such a PNI to both record efferent motor signals while concurrently stimulating afferent sensory axons in the same nerve is problematic. The micro-channel sieve electrode could also provide a stable, selective, neural interface with larger signal-to-noise levels that are less susceptible to concurrent stimulation artifact or other external noise effects. APPROACH: This study uses a computational model to compare recording levels of simulated ENGs across neural drive levels as well as basic control signals derived from the ENGs in both tfTIME and micro-channel sieve PNIs. A motor neuron pool model generated axon firing rates at a given neural drive. The time course of the corresponding extracellular currents of the myelinated motor axons were determined using core conductor axon models. Finite element models determined the contribution of the extracellular current from nodes of Ranvier on potentials recorded using each interface. Contributions from each node were combined to create the final ENG. MAIN RESULTS: ENGs recorded using the micro-channel sieves were shown to have much higher amplitudes compared to ENGs recorded using the tfTIMEs. Signal amplitudes also varied less as a function of axonal placement and spike timing, resulting in more consistent signals with amplitudes determined predominantly by neural drive. SIGNIFICANCE: Simulation results suggest that the micro-channel sieve provides higher quality control signals over tfTIME PNIs in decoding ENGs. Coupling these results with concurrent stimulation results of the companion paper (Part B: stimulation) suggests that the micro-channel sieve is an optimal bidirectional PNI.