bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preserved Tolerance to Lower‐Body Negative Pressure during Heat Stress in Individuals with Multiple Sclerosis
Authors: Huang Mu , Allen Dustin R , Keller David M , Fadel Paul J , Frohman Elliot M , Davis Scott L 
Published: November 2023

Multiple sclerosis (MS), a progressive neurological disease, can result in impairments in both the autonomic control of cardiovascular and thermoregulatory function. We tested the following hypotheses: (i) patients with MS (n=10) would exhibit diminished tolerance to a simulated hemorrhagic challenge compared to age, height, body weight, and sex matched healthy controls (CON, n=10) in normothermic, baseline conditions (NT, perfusing 34 °C water via tube‐lined suit) and (ii) this diminished tolerance would be exaggerated during a passive whole‐body heat stress (WBH, increased core temperature by 0.8 °C perfusing 48 °C water). Hemorrhage was simulated via progressive lower‐body negative pressure (LBNP) to presyncope and tolerance was quantified via a cumulative stress index (CSI). During NT, no differences were observed between MS and CON in response to LBNP (MS: 534±303, CON: 622±209 CSI; p=0.46). However, attenuated CSI reductions (% decline from NT) were revealed during WBH in MS compared to CON (MS: 29.9±23.4, CON: 58.6±21.8 % decline; p=0.01) suggesting a reduced impact of heat stress on LBNP tolerance in MS patients. One possible explanation for these findings is preserved fluid volume, as whole body sweat loss was lower in MS compared to CON (MS: 0.9±0.4, CON: 1.5±0.6 % body mass deficit; p=0.05). Contrary to our original hypotheses, these preliminary findings suggest LBNP tolerance was not different between groups at NT baseline and that individuals with MS had less of a decline in LBNP tolerance during WBH.Support or Funding InformationSupported by NIH (R15HL11722401) and NMSS (RG4696A3/2) grants.
The Effect of Exhaustive Exercise, Carbohydrate Ingestion and Muscle Glycogen Content on Exercise‐Induced Circulatory Immune Responses
Authors: Dent Jessica R , Ogden Henry , Hazeldine Jon , Stocks Ben , Zemp Martina , Harrison Paul , Philp Andrew 
Published: November 2023

Exercising in a state of reduced muscle glycogen content (“compete‐high, train‐low”) enhances metabolic adaptation in skeletal muscle. However, despite the increasing popularity of such regimes, how this training strategy affects post‐exercise immune disturbances and an athlete's susceptibility to acute upper respiratory tract infections (URTIs) is largely unknown. The present study therefore set out to investigate the influence of exhaustive exercise, carbohydrate (CHO) feeding and subsequent next‐day steady state (SS) exercise commenced in a ‘graded’ state of muscle glycogen availability on circulating immune markers. Eight healthy active males (mean ± SD: age 25 ± 2 yrs; height 176.3 ± 7.7 cm; body mass 78.7 ± 12.8 kg; 2 peak 45.6 ± 4.2 ml·kg‐1·min‐1) each completed three trials in a randomized crossover design. On each occasion, participants undertook an evening bout of muscle glycogen depleting cycle ergometry, before consuming 7 hours worth of CHO jelly and beverages at a rate of: 0.0 g.kg.h‐1 (LOW), 0.6 g.kg.h‐1 (MED) or 1.2 g.kg.h‐1 (HIG). The following morning, participants returned to perform one hour of SS cycling at 57% peak power output. Skeletal muscle biopsies were obtained pre‐depletion (trial 2), and immediately prior and post SS exercise. Blood samples were collected pre, post, 1 and 2 hours after both exhaustive and SS exercise bouts. Whole blood was used for the analysis of differential leukocyte counts and neutrophil function via the capacity for phagocytosis and production of superoxide following stimulation with opsonized E.Coli. The experimental design successfully produced three ‘graded’ levels of pre‐exercise muscle glycogen available prior to the commencement of SS exercise (p < 0.05). In each condition, lymphocyte/eosinophil count, neutrophil phagocytosis and oxidative burst were all suppressed following both exhaustive and SS exercise bouts (p < 0.05) when compared to pre‐depletion levels, whereas total leukocyte, neutrophil and monocyte counts were all increased (p < 0.05), and highest following SS exercise in the LOW trial (p < 0.05). To conclude, our data demonstrate little benefit for high or moderate CHO‐re‐feeding in the immediate hours following exhaustive exercise on immune function but lowered muscle glycogen may create greater immune disturbance following SS exercise. It may be suggested that CHO availability and its effect on exercise stress and tolerance, rather than a direct effect of CHO itself, confers benefits for immune function and an athlete's susceptibility to URTI's.Support or Funding InformationThis study was funded in part by a BBSRC New Investigator Award BB/L023547/1 to AP
Polyphenol Supplementation Does not Change the Post‐Resistance Exercise Circulating and Intramuscular TNF‐α or TNFR1 Response on Monocyte Subsets
Authors: Jajtner Adam , Hoffman Jay , Townsend Jeremy , Beyer Kyle , Varanoske Alyssa , Church David , Oliveira Leonardo , Herrlinger Kelli , Radom‐Aizik Shlomit , Fukuda David , Stout Jeffrey 
Published: November 2023

OBJECTIVEExamine the effect of a proprietary polyphenol blend (PPB) on the tumor necrosis factor – α (TNF‐α) and TNF receptor 1 (TNFR1) response to resistance exercise.METHODSUntrained men (n=38, 22.1±3.1 y; 174.0±7.9 cm; 77.8±14.5 kg) were randomized to: PPB (n=13), placebo (PL; n=15) or control (CON; n=10). PPB and PL were supplemented for 28 days prior to an acute bout of resistance exercise, consisting of 10 repetitions at 70% of the one repetition maximum for the squat (6 sets), leg press (4 sets) and leg extension (4 sets) exercises. Blood was obtained at pre (PRE), immediately (IP), 1 (1H), 5 (5H), 24 (24H) and 48 (48H) hours post‐exercise (PPB/PL), or rest (CON). Biopsies were obtained from the vastus lateralis at PRE, 1H, 5H and 48H. Plasma and intramuscular TNF‐α was assessed by multiplex assay. TNFR1 expression on classical (CLAS; CD14++/CD16−), intermediate (INT; CD14++/CD16+) and nonclassical (NC; CD14+/CD16+) circulating monocytes was assessed via flow cytometry. Repeated measures ANOVA were applied, and non‐normally distributed data were LN transformed. Area under the curve with respect to increase (AUCi) analyses were also performed. Data are presented as mean ± SD.RESULTSA time effect was observed for circulating (p=0.018), and intramuscular (p=0.021) TNF‐α. Circulating TNF‐α concentrations increased from PRE (19.4±16.7 pg·ml−1) to IP (23.3±22.7 pg·ml−1; p=0.026), while intramuscular protein content also increased from PRE (0.94±0.68 pg·mg−1) to IP (1.45±0.80 pg·mg−1; p=0.001). A time effect for TNFR1 expression on CLAS was observed (p<0.001), with changes from PRE at 1H (108.5±10.1%; p<0.001), 24H (115.5±24.8%; p=0.001) and 48H (105.6±12.8%; p=0.014). TNFR1 expression on CLAS AUCi was different between groups (p=0.050), with PPB (p=0.020) and PL (p=0.051) greater than CON. A time effect for TNFR1 expression on INT was observed (p<0.001), with changes from PRE at 1H (105.7±8.9%; p=0.001), and 24H (109.8±17.3%; p=0.002). TNFR1 expression on INT AUCi was different between groups (p=0.049) with PPB (p=0.020) and PL (p=0.048) greater than CON. A time effect was also observed for TNFR1 expression on NC (p=0.007), with changes from PR at 24H (108.0±16.0%; p=0.006). TNFR1 expression on NC AUCi was different between groups (p=0.034) with PPB (p=0.019) and PL (p=0.022) greater than CON.CONCLUSIONSData indicate the TNFR1 response to resistance exercise may be biphasic on CLAS and INT with increases at 1H, followed by a return to baseline at 5H, and increases again at 24H. Expression on NC, however, appear to be delayed, with increased expression only observed at 24H. Furthermore, chronic polyphenol supplementation does not appear to impact this post‐exercise response.Support or Funding InformationFunded by Kemin Foods, L.C.
Influence of physical exercise on skeletal muscle trophism and myostatin signaling in rats subjected to intermittent feeding
Authors: Martinez Paula F , Oliveira Ana Priscila C , Gois Priscilla B , Gomes Mariana J , Pagan Luana U , Morais Camila S , Muzili Nayara A , Ota Gabriel E , Carvalho Marianna R , Souza Albert S , Okoshi Katashi U , Okoshi Marina P , Oliveira‐Junior Silvio A 
Published: November 2023

BackgroundIntermittent feeding (IF) is often used as an alternative to caloric restriction and characterized by alternating cycles of ad libitum feeding and fasting. The main consequence of caloric restriction on skeletal muscle is fiber size reduction, which pathophysiological mechanism is not well known. This study aimed to evaluate the influence of exercise on skeletal muscle morphology and myostatin signaling in rats subjected to intermittent feeding.MethodsMale Wistar rats (n=40) were allocated into four groups: sedentary control (C‐S), control + physical exercise (C‐Ex), sedentary intermittent feeding (IF‐S), and intermittent feeding + physical exercise (IF‐Ex). The C‐S and C‐Ex groups were fed ad libitum, and IF‐S and IF‐Ex groups had ad libitum access to food on alternating days. Rats from C‐Ex and IF‐Ex underwent into a treadmill‐exercise protocol for 90 days. Functional capacity was assessed by maximal exercise test on treadmill. Myostatin and follistatin protein expression was evaluated by Western blot in soleus and gastrocnemius (white portion) muscles. Statistics: two‐way ANOVA and Tukey.ResultsFunctional capacity was improved in exercised groups compared to respective controls. Exercise, as an independent factor, reduced myostatin expression in gastrocnemius muscle (C‐S 1.0±0.3; IF‐S 0.9±0.3; C‐Ex 0.8±0.1; IF‐Ex 0.8±0.1). There was no difference between groups for myostatin expression in soleus muscle, and follistatin expression in both gastrocnemius and soleus muscle. Other results are shown in Table.ConclusionIntermittent feeding promotes a physical exercise‐reversible atrophy in soleus muscle, but not in white gastrocnemius muscle of rats. Although myostatin may be modulated by physical exercise, it does not seem to participate on intermittent feeding‐induced muscle atrophy.Support or Funding InformationFinancial support: CAPES

Variables
C‐S
IF‐S
C‐Ex
IF‐Ex

Gastrocnemius mass (g)
2.36±0.28
1.92±0.27*
2.35±0.17
2.12±0.13#†

Soleus mass (g)
0.18±0.03
0.14±02*
0.17±0.02
0.16±0.02

Gastrocnemius CSA (μm2)
3878±308
3156±434*
3667±270
3101±398†

Soleus CSA (μm2)
3982±543
3177±314*
3649±354
3617±160#

CSA: fiber cross‐sectional area. Mean ± standard deviation. Two‐way ANOVA and Tukey;
p<0.05 vs. C‐S;
p<0.05 vs. IF‐S;
p<0.05 vs. C‐Ex.
Strings attached: Sound perception and brain wiring enabled by cadherins
Authors: Sotomayor Marcos 
Published: November 2023

Cadherins form a large superfamily of proteins essential for morphogenesis, neuronal connectivity, and tissue integrity. Two atypical members of this superfamily, cadherin‐23 (cdh23) and protocadherin‐15 (pcdh15), are also involved in hereditary deafness and blindness. In the inner ear, these two proteins interact to form the tip link, a fine filament that pulls open transduction channels to initiate a cascade of events leading to sensory perception. Here we present structural, computational, and biophysical experiments that reveal unique properties of the tip link's extracellular cadherin (EC) repeats. Our crystal structures, simulations, and binding assays show how the N‐terminus of pcdh15 and several of its variants form a calcium‐dependent heterophilic complex with the N‐terminus of cdh23. In addition, structures and simulations of other domains of cdh23 and pcdh15 reveal unusual inter‐repeat linker regions that may alter the tertiary structure and elasticity of these proteins. Overall, our results provide a molecular view of tip link mechanics and identify the structural determinants of cdh23 and pcdh15 function in vertebrate mechanosensation.Support or Funding InformationNIH NIDCD and Alfred P. Sloan Foundation.
Muscle Activation Assessed with Electromyography is Suboptimal During Physical Therapy in Mechanically Ventilated Patients
Authors: Supinski Gerald S. , Netzel Paul F. , Valentine Emily N , Callahan Leigh Ann 
Published: November 2023

Physical therapy (PT) is a standard component of care for mechanically ventilated (MV) patients. Recent studies have raised concerns, however, that this treatment may be relatively ineffective. The purpose of the present study was to objectively analyze the effect of PT on leg strength in MV patients. Studies were performed on 22 MV patients receiving PT for 2 weeks. To assess PT intensity, we measured: (a) exercise duration, (b) PT types (range of motion, transfers, exercise machine usage, walking, resistance training), and (c) the intensity of muscle activation using wireless electromyogram (EMG) recordings of four leg muscles. To assess the response to PT, we measured quadriceps force generation evoked by magnetic femoral nerve stimulation. We found that response to PT was poor, and leg strength before and following PT (8.6 ± 3.4 and 7.6 ± 2.8 N) was not significantly different. EMG recordings indicated that patient effort during exercises was also poor. In particular, integrated normalized EMG activity fell substantially over time during training sessions in the majority of patients (the EMG index had a median of 30.3 (25–75% CI of 16.7–46.1) for the initial exercise and decreased to 18.1 (25–75% CI of 2.6–24.4) for the final exercise, p=0.039). There was dramatic patient‐to‐patient variation in the effort made during specific types of PT, resulting in substantial time spent performing ineffective exercises. We also found that, in many cases, the weakest patients received far less PT than patients with normal strength. These data provide a potential explanation why PT in MV patients is largely ineffective. We speculate that use of novel techniques to direct exercises (EMG targeting) and to accurately measure the response to PT (magnetic twitch assessment of strength) may dramatically improve responses of MV patients to PT.Support or Funding InformationR01HL113494, 5I01BX002132, R01HL112085
An analysis of how consumer physical activity monitors are used in biomedical research
Authors: Wright Stephen P , Collier Scott R , Brown Tyish S , Sandberg Kathryn 
Published: November 2023

BACKGROUNDBiomedical researchers are very interested in measuring physical activity because sedentary lifestyle and lack of physical activity are well‐established risk factors for chronic disease and adverse health outcomes. Many consumer physical activity monitors have accuracies similar to research‐grade monitors for measuring steps and offer a relatively new tool for measuring physical activity in an ecological setting.AIMTo analyze how consumer physical activity monitors are currently used in biomedical research.METHODSearches were conducted in Ovid Medline, PubMed Medline, clinicaltrials.gov, and NIH RePorter using search terms including Fitbit, Jawbone, Apple watch, Garmin, Polar, Microsoftband, Misfit, Nike, Withings, and Xiaomi. Results were quantitated by category: condition/topic, intervention, enrollment status, study type and design, participant age, funding mechanism, and primary outcome.RESULTSFitbit devices were the most common consumer physical activity monitors used in published work (89%), clinical trials (83%), and NIH‐funded research (95%). Validity studies represented the plurality (19/40) of published studies involving consumer physical activity monitors. The design of the majority of clinical trials (116/127) and unique NIH‐funded grants (20/25) involving Fitbit are interventional. The most common primary outcome measure reported in clinical trials using Fitbit is physical activity (50/127), with biomarkers of health (e.g., blood pressure, HbA1c, fasting glucose) being the second most prominent. The most common clinical conditions studied in clinical trials are mental and brain related (74/127), second most being body weight related (62/127).CONCLUSIONThe current state and potential growth of the consumer monitor technology is transforming biomedical research, and is enabling us to ask new and more granular questions about physical activity in health and disease.Support or Funding InformationThis work was supported by the following grants: TL1‐TR001431 (SPW), UL1‐TR001409 (TSHB, SPW, SRC, KS) and R01‐HL119380 (KS).
ADRB2 Variations do not Influence Body Composition in Duchenne Muscular Dystrophy
Authors: Kelley Eli F , Uithoven Katelyn E , Zavala Hanan , Karachunski Peter I , Snyder Eric M 
Published: November 2023

IntroductionDuchenne muscular dystrophy (DMD) is an inherited x‐link disease caused by the deletion of the dystrophin gene. DMD is characterized by progressive muscle weakness and degeneration of skeletal, cardiac and respiratory muscles resulting in severe functional impairment. The beta‐2 adrenergic receptor (ADRB2) plays a functional role in muscle size, strength and regeneration through regulation of multiple downstream mechanisms. Multiple polymorphisms of the ADRB2 have been identified as including a glycine (Gly) for arginine (Arg) substitution at amino acid 16. This polymorphism (Gly16) has been shown to have higher receptor density on lymphocytes and be more resistant to receptor down regulation. Although not specifically studied previously, human subjects with the Gly16 polymorphism tend to have a greater body mass index, despite greater fitness levels, possibly suggesting greater muscle mass. Therefore, the Gly16 polymorphism may attenuate skeletal muscle degeneration.PurposeTo investigate the relationship between ADRB2 genotype and body composition in DMD patients.MethodsSixteen patients were recruited through the University of Minnesota Fairview Clinic. DNA was collected via buccal swabs and analyzed for ADRB2 genotype. Medical records were then accessed to obtain retrospective data on dual energy x‐ray absorptiometry (DEXA) body composition measures.ResultsThere were no differences between genotype groups in age, height, weight, or BMI (age = 10.8 ± 2.8yrs, 9.8 ± 3.7yrs, 10.9 ± 3.5yrs, height = 138.1 ± 14.6cm, 130.2 ± 17.1cm, 136.6 ± 17.9cm, weight = 52.8 ± 26.5kg, 42.3 ± 25.1kg, 44.8 ± 19.3kg, and BMI = 26.5 ± 7.6, 23.2 ± 9.1, 22.8 ± 5.9, for AA, AG, and GG, respectively). Additionally, there were no differences between genotype groups in lower lumbar density (L1–L4), total body density (TBD), lean body mass (LBM), or lean body mass corrected for body surface area (LBM/BSA) (L1–L4 = 0.74 ± 0.16gm/cm2, 0.62 ± 0.12gm/cm2, 0.68 ± 0.09gm/cm2, TBD = 0.74 ± 0.11gm/cm2, 0.66 ± 0.13gm/cm2, 0.64 ± 0.01gm/cm2, LBM = 55.3 ± 16.7%, 67.7 ± 16.9%, 65.5 ± 19.9%, LBM/BSA = 43.4 ± 23.7, 66 ± 33.8, 59.1 ± 33.8, for AA, AG, and GG, respectively).ConclusionsAlthough ADRB2 genotype has been implicated in the regulation of muscle size and strength, these data suggest ADRB2 genotype does not influence body composition in DMD.Support or Funding InformationNIH grant: 5R01HL108962‐03
Transient cerebral ischemic stroke activates multiple catabolic signaling pathways in skeletal muscle
Authors: Tuntevski Kiril , Alway Stephen E. , Mohamed Junaith S. 
Published: November 2023

Stroke is the fifth leading cause of death in the United States, and even with optimal acute therapy, about two‐thirds of the patients remain in a state of incomplete recovery after stroke. Skeletal muscle is the primary target organ of stroke after the brain, therefore muscle atrophy and dysfunction are the leading cause of the functional disability in stroke patients. However, the underlying mechanism that causes the loss of muscle mass and function after stroke have not been investigated in detail. The objective of this study is to identify the mechanism that initiates muscle wasting and impairment in a mouse model of ischemic stroke. Using a mouse model of transient middle cerebral artery occlusion (tMCAO), changes in various catabolic activation in muscle tissue was studied. Muscle wasting (muscle mass), muscle catabolism, and proteasome activity were assessed. Post‐stroke mice displayed severe muscle wasting. Catabolic signaling such as apoptosis, atrophy and autophagy, and proteasome pathways were activated in the ipsilateral leg when compare to the contralateral leg in the post‐stroke mice. Our study indicates that muscle wasting after ischemic stroke is caused mainly by the synergetic activation of multiple catabolic pathways, suggesting that identification of the upstream factor (s) that initiates activation of the above catabolic pathways in response to stroke might provide improved treatment tactics for the stroke patients.Support or Funding InformationWVU CoBRE Pilot Grant P20 GM109098‐03 (Simpkins, J; PI)
Resistance training with short interval does not induce skeletal muscle hypertrophy in rats
Authors: Takegaki Junya , Kotani Takaya , Ogasawara Riki , Tsutaki Arata , Nakazato Koichi , Ishii Naokata 
Published: November 2023

Resistance training is an effective tool for increasing the skeletal muscle mass and strength. The resistance training effect is recognized to depend on the training frequency, together with intensity, volume, etc. However, the detailed response according to the training frequency remains unclear.PurposeTo see changes in skeletal muscle hypertrophy and relating factors after equal sessions of resistance exercise by changing the training interval.MethodsMale Sprague‐Dawley rats were randomly assigned into three groups: resistance‐trained with 18 bouts at interval of 72h (72H), 24h (24H), and 8h (8H). The resistance exercise consisted of 50 repetitions of maximal isometric contraction of the gastrocnemius muscle. The right gastrocnemius muscle was used as trained muscle, and the left was used as internal control. The muscle contraction was induced by transcutaneous electrical stimulation under anesthesia. Muscle samples were collected 48h after the final exercise session, and kept frozen until analysis.ResultsGastrocnemius wet weight was increased in 72H and 24H, but not in 8H. Mitochondria content was increased in 72H and 24H, but not in 8H. The protein ubiquitination was observed in all groups, and the ubiquitination was increased with shortening of training interval.ConclusionThe present results suggest that resistance training with 8h interval does not cause skeletal muscle hypertrophy, and the hostile environment for anti‐catabolism is one of the possible causes for this.Support or Funding InformationThis work was supported by grants‐in‐aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (15H03078 to N.I.).