Acceptability of Performing Resistance Exercise Breaks in the Workplace to Break Up Prolonged Sedentary Time: A Randomized Control Trial in U.S. Office Workers and Students.

We investigated the acceptability of bodyweight resistance exercise breaks (REB) to disrupt prolonged sedentary behavior in the workplace. Twenty-nine individuals completed a REB, where they performed 3-min REB 4, 8, and 16 times on days 1-2, 3-4, and 5 of the workweek, respectively, and a control condition (i.e., SIT). Productivity was assessed on days 1 and 5 each week. The acceptability of each REB frequency was assessed. When asked to complete 4, 8, and 16 REB, participants completed (mean values) 3.2, 6.2, and 9.2 REB/day, respectively. Moreover, 88%, 40%, and 9% of participants expressed that the 4-, 8-, and 16-REB frequencies were acceptable, respectively. Decision-making ability and concentration levels increased from day 1-5 of the REB week (p=0.048) but were stable during SIT. REB (4/day) are highly acceptable and could be a promising intervention strategy for reducing occupational sitting, thus decreasing sedentary-behavior-induced risk.

Acute effects of commercial energy drink consumption on exercise performance and cardiovascular safety: a randomized, double-blind, placebo-controlled, crossover trial.

The aim of this study was to examine the acute effects of a non-caloric energy drink (C4E) compared to a traditional sugar-containing energy drink (MED) and non-caloric placebo (PLA) on exercise performance and cardiovascular safety. Thirty healthy, physically active males (25 ± 4 y) completed three experimental visits under semi-fasted conditions (5-10 h) and in randomized order, during which they consumed C4E, MED, or PLA matched for volume, appearance, taste, and mouthfeel. One hour after drink consumption, participants completed a maximal, graded exercise test (GXT) with measurement of pulmonary gases, an isometric leg extension fatigue test (ISOFTG), and had their cardiac electrical activity (ECG), leg blood flow (LBF), and blood pressure (BP) measured throughout the visit. Neither MED nor C4E had an ergogenic effect on maximal oxygen consumption, time to exhaustion, or peak power during the GXT (p > 0.05). Compared to PLA, MED reduced fat oxidation (respiratory exchange ratio (RER) +0.030 ± 0.01; p = 0.026) during the GXT and did not influence ISOFTG performance. Compared to PLA, C4E did not alter RER (p = 0.94) and improved impulse during the ISOFTG (+0.658 ± 0.25 V·s; p = 0.032). Relative to MED, C4E did not significantly improve gas exchange threshold (p = 0.05-0.07). Both MED and C4E increased systolic BP at rest (+7.1 ± 1.2 mmHg; p < 0.001 and + 5.7 ± 1.0 mmHg; p < 0.001, respectively), C4E increased SBP post-GXT (+13.3 ± 3.8 mmHg; p < 0.001), and MED increased SBP during recovery (+3.2 ± 1.1 mmHg; p < 0.001). Neither MED nor C4E influenced ECG measures (p ≥ 0.08) or LBF (p = 0.37) compared to PLA. C4E may be more efficacious for improving performance in resistance-type tasks without altering fat oxidation under semi-fasted conditions during fatiguing exercise bouts, but promotes similar changes in BP and HR to MED.

The effects of sleep disruption on metabolism, hunger, and satiety, and the influence of psychosocial stress and exercise: A narrative review.

Sleep deficiency is a ubiquitous phenomenon among Americans. In fact, in the United States, ∼78% of teens and 35% of adults currently get less sleep than recommended for their age-group, and the quality of sleep appears to be getting worse for many. The consequences of sleep disruption manifest in a myriad of ways, including insulin resistance and disrupted nutrient metabolism, dysregulation of hunger and satiety, and potentially increased body weight and adiposity. Consequently, inadequate sleep is related to an increased risk of various cardiometabolic diseases, including obesity, diabetes, and heart disease. Exercise has the potential to be an effective therapeutic to counteract the deleterious effects of sleep disruption listed above, whereas chronic psychosocial stress may causally promote sleep disruption and cardiometabolic risk. Here, we provide a narrative review of the current evidence on the consequences of short sleep duration and poor sleep quality on substrate metabolism, circulating appetite hormones, hunger and satiety, and weight gain. Secondly, we provide a brief overview of chronic psychosocial stress and its impact on sleep and metabolic health. Finally, we summarise the current evidence regarding the ability of exercise to counteract the adverse metabolic health effects of sleep disruption. Throughout the review, we highlight areas where additional interrogation and future exploration are necessary.

Novel Energy Drink Improves Cognitive Function and Mood, without Influencing Myocardial Oxygen Demand or Ventricular Repolarization in Adult Gamers: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

OBJECTIVES: To examine the efficacy of acute consumption of a novel energy drink (C4S) versus placebo for improving cognitive and gaming performance and mood. Secondarily, we examined the cardiovascular safety profile of acute C4S consumption. METHODS: Forty-five healthy, young adult video gamers completed two experimental visits in randomized order where they consumed either C4S or a placebo and then completed a validated battery of neurocognitive tests, played five video games, and completed a mood state survey. Blood pressure (BP), heart rate (HR), oxygen saturation, and electrocardiogram measurements were taken at baseline and repeated throughout each visit. RESULTS: Acute consumption of C4S improved cognitive flexibility (absolute mean or median difference [95% CI] = +4.3 [2.2-6.4]; p < 0.001; d = 0.63), executive function (+4.3 [2.3-6.3]; p < 0.001; d = 0.63), sustained attention (+2.1 [0.6-3.6]; p = 0.01; d = 0.44), motor speed (+2.9 [0.8-4.9]; p < 0.001; d = 0.44), psychomotor speed (+3.9 [0.1-7.7]; p = 0.04; d = 0.32) working memory (+1.0 [0.1-1.9]; p = 0.02; d = 0.35), and performance in the two-dimensional visuospatial game Tetris (+463 [-419-2,065] pts; p = 0.049; d = 0.30) compared to placebo. C4S also improved Fatigue-Inertia (-1 [-3-0]; p = 0.004; d = 0.45), Vigor-Activity (+2.4 [1.3-3.6]; p < 0.001; d = 0.64), Friendliness (+0 [0-1]; p = 0.04; d = 0.32), and Total Mood Disturbance (-3 [-6-0]; p = 0.002; d = 0.44). BP increased slightly in C4S versus placebo, while HR decreased from baseline to post-drink in the C4S condition. Rate-pressure-product was higher in C4S versus placebo independent of time but did not increase from baseline. There was no effect on corrected QT interval. CONCLUSION: Acute consumption of C4S was efficacious for cognitive performance, visuospatial gaming performance, and mood enhancement, and had no effect on myocardial oxygen demand or ventricular repolarization, despite being associated with increases in BP.

Resistance exercise lowers blood pressure and improves vascular endothelial function in individuals with elevated blood pressure or stage-1 hypertension.

Lifestyle modifications are the first-line treatment recommendation for elevated blood pressure (BP) or stage-1 hypertension (E/S1H) and include resistance exercise training (RET). The purpose of the current study was to examine the effect of a 9-wk RET intervention in line with the current exercise guidelines for individuals with E/S1H on resting peripheral and central BP, vascular endothelial function, central arterial stiffness, autonomic function, and inflammation in middle-aged and older adults (MA/O) with untreated E/S1H. Twenty-six MA/O adults (54 ± 6 yr; 16 females/10 males) with E/S1H engaged in either 9 wk of 3 days/wk RET (n = 13) or a nonexercise control (Con; n = 13). Pre- and postintervention measures included peripheral and central systolic (SBP and cSBP) and diastolic BP (DBP and cDBP), flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), cardiovagal baroreflex sensitivity (BRS), cardiac output (CO), total peripheral resistance (TPR), heart rate variability (HRV), and C-reactive protein (CRP). RET caused significant reductions in SBP {mean change ± 95% CI = [-7.9 (-12.1, -3.6) mmHg; P < 0.001]}, cSBP [6.8 (-10.8, -2.7) mmHg; P < 0.001)], DBP [4.8 (-10.3, -1.2) mmHg; P < 0.001], and cDBP [-5.1 (-8.9, -1.3) mmHg; P < 0.001]; increases in FMD [+2.37 (0.61, 4.14)%; P = 0.004] and CO [+1.21 (0.26, 2.15) L/min; P = 0.006]; and a reduction in TPR [-398 (-778, -19) mmHg·s/L; P = 0.028]. RET had no effect on cfPWV, BRS, HRV, or CRP relative to Con (P ≥ 0.20). These data suggest that RET reduces BP in MA/O adults with E/S1H alongside increased peripheral vascular function and decreased TPR without affecting cardiovagal function or central arterial stiffness.NEW & NOTEWORTHY This is among the first studies to investigate the effects of chronic resistance exercise training on blood pressure (BP) and putative BP regulating mechanisms in middle-aged and older adults with untreated elevated BP or stage-1 hypertension in a randomized, nonexercise-controlled trial. Nine weeks of resistance exercise training elicits 4- to 8-mmHg improvements in systolic and diastolic BP alongside improvements in vascular endothelial function and total peripheral resistance without influencing central arterial stiffness or cardiovagal function.

Progressive iso-inertial resistance exercise promotes more favorable cardiovascular adaptations than traditional resistance exercise in young adults.

We compared the cardiovascular adaptations to resistance training (RT) using either traditional isotonic or iso-inertial resistance exercise in a randomized controlled study. Thirty-one healthy young adults (means ± SD, age = 24 ± 3 yr) completed 10 wk of traditional isotonic RT (TRT; n = 7 female/5 male), iso-inertial flywheel RT (FWRT; n = 7 female/4 male), or a habitual activity control (Con; n = 5 female/3 male). Before and following the intervention period, blood pressure, blood pressure reactivity, flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), baroreflex sensitivity (BRS), and heart rate variability (RMSSD) were assessed. TRT and FWRT similarly improved isometric muscle strength. TRT significantly increased systolic blood pressure reactivity during isometric exercise compared with both FWRT (mean difference ± 95% CI, +10.8 ± 8.8 mmHg) and Con (+11.8 ± 9.1 mmHg). Cardiovagal BRS was significantly reduced in TRT versus FWRT (-6.82 ± 4.9 ms/mmHg; P = 0.006) but not between TRT versus Con (P = 0.12) or FWRT versus Con (P = 0.43). Resting heart rate (RHR) and RMSSD worsened in TRT compared with FWRT (RHR, +8 ± 5.8 beats/min, P = 0.006; RMSSD, -22.3 ± 15.6 ms, P = 0.004). Changes in BRS and RMSSD were associated with changes in blood pressure reactivity in the RT groups (r = -0.51 to -0.52). There were no significant changes in FMD or cfPWV in any group (P > 0.13). In conclusion, 10 wk of TRT and FWRT resulted in similar improvements in strength, but TRT caused impairments in blood pressure reactivity compared with FWRT and Con and parasympathetic nervous system activity compared with FWRT.NEW & NOTEWORTHY We characterized the cardiovascular effects of traditional, isotonic resistance training (TRT) versus flywheel-based iso-inertial resistance training (FWRT) in young healthy adults. Both TRT and FWRT improved strength, but TRT reduced cardiovagal baroreflex sensitivity and heart rate variability while increasing exercising blood pressure compared with FWRT. Our data indicate that TRT and FWRT result in different cardiovascular adaptations, where TRT, but not FWRT, may impair cardiovagal function and blood pressure reactivity in healthy, active young adults.

The Diagnostic, Therapeutic and Prognostic Relevance of Neutrophil Extracellular Traps in Polytrauma.

Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research.

Acute effects of daily step count on postprandial metabolism and resting fat oxidation: a randomized controlled trial.

To examine the effects of daily step count on same-day fat oxidation and postprandial metabolic responses to an evening high-fat mixed meal (HFMM). Ten healthy participants (5 females, 30 ± 7 yr) completed four different daily step counts-2,000 (2 K), 5,000 (5 K), 10,000 (10 K), and 15,000 (15 K) steps-on separate days in randomized order. On experimental days, participants ate the same meals and walked all steps on an indoor track at a pace of 100 steps/min in three roughly equal bouts throughout the day. After the final walking bout, participants' resting energy expenditure (REE), respiratory exchange ratio (RER), and fat oxidation rate (FATOX) were measured. Blood samples were obtained before (BL) and 30-, 60-, 90-, 120-, and 240-min following consumption of an HFMM (960 kcal; 48% fat) to measure triglycerides (i.e., postprandial lipemia; PPL), nonesterified fatty acids (NEFAs), insulin, and glucose. Two-way ANOVAs indicated condition effects where PPL was significantly higher after 2 K versus 10 K (+23 ± 8 mg/dL, P = 0.027), and NEFAs were significantly higher after 15 K versus 2 K (+86 ± 23 µmol/L; P = 0.006). No differences were found for insulin, glucose, or REE among conditions (all P > 0.124). Similarly, RER (P = 0.054; ηp2 = 0.24) and FATOX (P = 0.071; ηp2 = 0.23) were not significantly different among conditions. In young adults, 10 K steps elicited the greatest decrease in PPL, an established cardiovascular disease risk factor. NEFA levels were highest after the 15 K condition, likely due to alterations in adipose tissue lipolysis or lipoprotein lipase activity with increased activity.NEW & NOTEWORTHY This randomized controlled trial demonstrated that walking 10,000, compared with 2,000, steps/day significantly reduced postprandial lipemia (PPL), an independent predictor of cardiovascular disease (CVD) following same-day evening meal consumption. These experimental data support walking 10,000 steps/day to lower CVD risk.

Sostdc1 Suppression in the Absence of Sclerostin Potentiates Anabolic Action of Cortical Bone in Mice.

The development of Wnt-based osteoanabolic agents has progressed rapidly in recent years, given the potent effects of Wnt modulation on bone homeostasis. Simultaneous pharmacologic inhibition of the Wnt antagonists sclerostin and Dkk1 can be optimized to create potentiated effects in the cancellous bone compartment. We looked for other candidates that might be co-inhibited along with sclerostin to potentiate the effects in the cortical compartment. Sostdc1 (Wise), like sclerostin and Dkk1, also binds and inhibits Lrp5/6 coreceptors to impair canonical Wnt signaling, but Sostdc1 has greater effects in the cortical bone. To test this concept, we deleted Sostdc1 and Sost from mice and measured the skeletal effects in cortical and cancellous compartments individually. Sost deletion alone produced high bone mass in all compartments, whereas Sostdc1 deletion alone had no measurable effects on either envelope. Mice with codeletion of Sostdc1 and Sost had high bone mass and increased cortical properties (bone mass, formation rates, mechanical properties), but only among males. Combined administration of sclerostin antibody and Sostdc1 antibody in wild-type female mice produced potentiation of cortical bone gain despite no effect of Sostdc1 antibody alone. In conclusion, Sostdc1 inhibition/deletion can work in concert with sclerostin deficiency to improve cortical bone properties. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Progressive exercise training improves cardiovascular psychophysiological outcomes in young adult women with a history of adverse childhood experiences.

Adverse childhood experiences (ACEs) are early-life psychosocial stressors that are associated with poorer mental health and increased cardiovascular disease (CVD) risk in a dose-dependent manner. We examined the feasibility of an 8-wk combined aerobic and resistance exercise training program to improve systolic (SBP) and diastolic blood pressure (DBP), serum endothelin-1 (ET-1), resilience, hope agency, and hope pathways in young women with ACEs. Forty-two healthy women (21 ± 3 yr) with ≥4 (ACE+; n = 28) or 0 ACEs (ACE-; n = 14) participated in this study. Women with ACEs were randomly assigned to an exercise (ACE+EXT; n = 14) or nonexercise control (ACE+CON; n = 14) group, whereas all ACE- participants were assigned to a nonexercise control (n = 14) group. Hope agency and DBP did not change in any group (P ≥ 0.43), but hope pathways improved only in ACE+EXT (means ± SE change; +1.6 ± 0.74 au, P = 0.032, Hedges' g = 0.53). ET-1 decreased in ACE+EXT only (-0.31 ± 0.15 pg/mL, P = 0.043, g = 0.46). Although the interactions for resilience and SBP did not reach significance (P = 0.05-0.06), forced post hoc analyses indicated that resilience improved (+4.9 ± 1.9 au, P = 0.012, g = 0.64) and SBP tended to improve (-4.0 ± 2.0 mmHg, P = 0.053, g = 0.51) in ACE+EXT only. There were significant associations between changes in hope pathways and SBP (ρ = -0.43, P = 0.023) and ET-1 (ρ = -0.53, P = 0.005), and between changes in SBP and ET-1 (ρ = 0.49; P = 0.012) in the ACE+ group. In summary, structured exercise training reduces serum ET-1 levels, improves positive psychological coping, and may improve SBP in young women with ACEs. The relationships among the changes in hope pathways, SBP, and ET-1 suggest a cardiovascular psychophysiological relationship in young women with ACEs.NEW & NOTEWORTHY This randomized controlled pilot trial shows, for the first time, that 8 wk of structured, progressive exercise training lowers serum endothelin-1 (ET-1) and improves positive psychological coping in young women with significant early-life psychosocial stress. Furthermore, the observed associations among changes in psychological attributes, ET-1, and systolic blood pressure signify a potential interplay between positive psychology and cardiovascular disease risk among women with adverse childhood experiences.

Metabolic and microvascular function assessed using near-infrared spectroscopy with vascular occlusion in women: age differences and reliability.

NEW FINDINGS: What is the central question of this study? Can the near-infrared spectroscopy with vascular occlusion test (NIRS-VOT) reliably measure skeletal muscle metabolic and microvascular function in women? What is the main finding and its importance? The NIRS-VOT can be used as a reliable technique for the assessment of skeletal muscle metabolism and microvascular function in women, with reliability being generally greater in younger women. These findings have important implications for the planning and development of future studies employing the NIRS-VOT in women, and provide insights into the effects of age on these parameters in women specifically. ABSTRACT: We investigated the test-retest reliability of, and age-related differences in, markers of skeletal muscle metabolism and microvascular function derived from the near-infrared spectroscopy with vascular occlusion test (NIRS-VOT) in younger women (YW) and middle-aged and older women (MAOW). Seventeen YW (age 23 ± 4 years) and 17 MAOW (age 59 ± 8 years) completed this study. Participants completed identical experimental visits separated by ∼4 weeks during which the NIRS-VOT was used to quantify the occlusion slope, minimum and maximum tissue saturation, ischaemic index, reperfusion magnitude, the reperfusion and 10-s reperfusion slopes (slope 2 and slope 210-s ), time to max tissue saturation, and area under the reperfusion curve using the local tissue oxygen saturation signal. Except for slope 210-s (intraclass correlation coefficient (ICC) = 0.37; coefficient of variation (CV) = 31%), time to max tissue saturation (ICC = 0.21), and ischaemic index (ICC = 0.37) for MAOW, all of the NIRS variables demonstrated good to excellent relative reliability for the YW (ICCs = 0.74-0.86) and the MAOW (ICCs = 0.51-0.87), with CVs of 2-21% and 2-22%, respectively. The occlusion slope was significantly lower, indicating accelerated deoxygenation, while maximum tissue saturation, reperfusion magnitude, and ischaemic index were significantly higher in YW versus MAOW. No other group differences were found. In conclusion, our data support the use of the NIRS-VOT as a simple, reliable, non-invasive technique for the assessment of peripheral skeletal muscle metabolism and microvascular function in women, with the reliability being generally greater in YW versus MAOW. Further, our data suggest that ageing is associated with lower skeletal muscle metabolism and microvascular hyperaemic responsiveness in women.

Targeting Sclerostin and Dkk1 at Optimized Proportions of Low-Dose Antibody Achieves Similar Skeletal Benefits to Higher-Dose Sclerostin Targeting in the Mature Adult and Aged Skeleton.

Age-associated low bone mass disease is a growing problem in the US. Development of osteoanabolic therapies for treating skeletal fragility has lagged behind anti-catabolic therapies, but several bone-building molecules are clinically available. We reported previously that antibody-based neutralization of the Lrp5/Lrp6 inhibitor Dkk1 has minimal effects on bone gain, but can potentiate the already potent osteoanabolic effects of sclerostin inhibition (another Lrp5/Lrp6 inhibitor highly expressed by osteocytes). In this communication, we test whether an optimized ratio of sclerostin and Dkk1 antibodies (Scl-mAb and Dkk1-mAb, respectively), administered at low doses, can maintain the same bone-building effects as higher dose Scl-mAb, in adult (6 months of age) and aged (20 months of age) wild-type mice. A 3:1 dose of Scl-mAb:Dkk1-mAb at 12.5 mg/kg was equally efficacious as 25 mg/kg of Scl-mAb in both age groups, using radiographic (DXA, µCT), biomechanical, (3-point bending tests), and histological (fluorochrome-based bone formation parameters) outcome measures. For some bone properties, including trabecular thickness and bone mineral density in the spine, and endocortical bone formation rates in the femur, the 3:1 treatment was associated with significantly improved skeletal properties compared to twice the dose of Scl-mAb. Cortical porosity in aged mice was also reduced by both Scl-mAb and low-dose 3:1 treatment. Overall, both treatments were efficacious in the mature adult (6 mo.) and aged (20 mo.) skeletons, suggesting Wnt targeting is a viable strategy for improving skeletal fragility in the very old. Further, the data suggest that low dose of combination therapy can be at least equally efficacious as higher doses of Scl-mAb monotherapy.

Contextual Effects of Traumatic Brain Injury on the Connectome: Differential Effects of Deployment- and Non-Deployment-Acquired Injuries.

OBJECTIVE: To identify differential effects of mild traumatic brain injury (TBI) occurring in a deployment or nondeployment setting on the functional brain connectome. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: In total, 181 combat-exposed veterans of the wars in Iraq and Afghanistan ( n = 74 with deployment-related mild TBI, average time since injury = 11.0 years, SD = 4.1). DESIGN: Cross-sectional observational study. MAIN MEASURES: Mid-Atlantic MIRECC (Mid-Atlantic Mental Illness Research, Education, and Clinical Center) Assessment of TBI, Clinician-Administered PTSD Scale, connectome metrics. RESULTS: Linear regression adjusting for relevant covariates demonstrates a significant ( P < .05 corrected) association between deployment mild TBI with reduced global efficiency (nonstandardized ß = -.011) and degree of the K-core (nonstandardized ß = -.79). Nondeployment mild TBI was significantly associated with a reduced number of modules within the connectome (nonstandardized ß = -2.32). Finally, the interaction between deployment and nondeployment mild TBIs was significantly ( P < .05 corrected) associated with increased mean (nonstandardized ß = 9.92) and mode (nonstandardized ß = 14.02) frequency at which connections occur. CONCLUSIONS: These results demonstrate distinct effects of mild TBI on the functional brain connectome when sustained in a deployment versus nondeployment context. This is consistent with findings demonstrating differential effects in other areas such as psychiatric diagnoses and severity, pain, sleep, and cognitive function. Furthermore, participants were an average of 11 years postinjury, suggesting these represent chronic effects of the injury. Overall, these findings add to the growing body of evidence, suggesting the effects of mild TBI acquired during deployment are different and potentially longer lasting than those of mild TBI acquired in a nondeployment context.

Recursive Debility: Symptoms, Patient Activism, and the Incomplete Medicalization of ME/CFS.

This article examines the contestation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Lacking consistent diagnostic definitions, agreed-on biological indicators, or approved treatments, ME/CFS is an incompletely medicalized condition. It is defined by intractable and debilitating exhaustion after any form of exertion. Through an ethnographic exploration of an American ME/CFS patient activist group, I develop the concept of "recursive debility." Symptoms form the very basis for disease activist groupings in the absence of biomarkers, but they also present a significant barrier to traditional forms of activism. Ironically, then, debilitation blocks the means through which debilitation might end. Patients contest systems of knowledge but always in bodies that experience exhaustion without end. This article presents a disability studies intervention in suggesting that the recursivity of debility demonstrates the profound interdependence of the bodily aspects of impairment and the sociopolitical aspects of disability. [ME/CFS, chronic illness, medicalization, symptoms, debility].

The contributory role of vascular health in age-related anabolic resistance.

Sarcopenia, or the age-related loss of skeletal muscle mass and function, is an increasingly prevalent condition that contributes to reduced quality of life, morbidity, and mortality in older adults. Older adults display blunted anabolic responses to otherwise anabolic stimuli-a phenomenon that has been termed anabolic resistance (AR)-which is likely a casual factor in sarcopenia development. AR is multifaceted, but historically much of the mechanistic focus has been on signalling impairments, and less focus has been placed on the role of the vasculature in postprandial protein kinetics. The vascular endothelium plays an indispensable role in regulating vascular tone and blood flow, and age-related impairments in vascular health may impede nutrient-stimulated vasodilation and subsequently the ability to deliver nutrients (e.g. amino acids) to skeletal muscle. Although the majority of data has been obtained studying younger adults, the relatively limited data on the effect of blood flow on protein kinetics in older adults suggest that vasodilatory function, especially of the microvasculature, strongly influences the muscle protein synthetic response to amino acid feedings. In this narrative review, we examine evidence of AR in older adults following amino acid and mixed meal consumption, examine the evidence linking vascular dysfunction and insulin resistance to age-related AR, review the influence of nitric oxide and endothelin-1 on age-related vascular dysfunction as it relates to AR, briefly review the potential causal role of arterial stiffness in promoting skeletal muscle microvascular dysfunction and AR, and provide a brief overview and future considerations for research examining age-related AR.

REadmission PREvention in SepSis: Development and Validation of a Prediction Model.

ABSTRACT: Hospital 30-day readmissions remain a major quality and cost indicator. Traditional readmission risk scores, such as LACE (length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits), may be suboptimal in special patient populations, such as those with sepsis. As sepsis survivorship improves, there is a need to determine which variables might be associated with a decrease in 30-day readmission. We completed a retrospective analysis reviewing patients with sepsis who had unplanned 30-day readmissions. Multivariate regression analysis was performed for the REadmission PREvention in SepSis (REPRESS) model, which evaluated age, length of stay, Charlson disease count, Richmond Agitation-Sedation Scale score, discharge to a skilled nursing facility, and mobility for predictive significance in hospital readmission. Our REPRESS model performed better when compared with LACE for predicting readmission risk in a sepsis population.

Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span.

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the "Guttman Neuro Personal Trainer"®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.

Acquisition of Surface EMG Using Flexible and Low-Profile Electrodes for Lower Extremity Neuroprosthetic Control.

For persons with lower extremity (LE) amputation, acquisition of surface electromyography (sEMG) from within the prosthetic socket remains a significant challenge due to the dynamic loads experienced during the gait cycle. However, these signals are critical for both understanding the clinical effects of LE amputation and determining the desired control trajectories of active LE prostheses. Current solutions for collecting within-socket sEMG are generally (i) incompatible with a subject's prescribed prosthetic socket and liners, (ii) uncomfortable, and (iii) expensive. This study presents an alternative within-socket sEMG acquisition paradigm using a novel flexible and low-profile electrode. First, the practical performance of this Sub-Liner Interface for Prosthetics (SLIP) electrode is compared to that of commercial Ag/AgCl electrodes within a cohort of subjects without amputation. Then, the corresponding SLIP electrode sEMG acquisition paradigm is implemented in a single subject with unilateral transtibial amputation performing unconstrained movements and walking on level ground. Finally, a quantitative questionnaire characterizes subjective comfort for SLIP electrode and commercial Ag/AgCl electrode instrumentation setups. Quantitative analyses suggest comparable signal qualities between SLIP and Ag/AgCl electrodes while qualitative analyses suggest the feasibility of using the SLIP electrode for real-time sEMG data collection from load-bearing, ambulatory subjects with LE amputation.

MEG source imaging detects optogenetically-induced activity in cortical and subcortical networks.

Magnetoencephalography measures neuromagnetic activity with high temporal, and theoretically, high spatial resolution. We developed an experimental platform combining MEG-compatible optogenetic techniques in nonhuman primates for use as a functional brain-mapping platform. Here we show localization of optogenetically evoked signals to known sources in the superficial arcuate sulcus of cortex and in CA3 of hippocampus at a resolution of 750 µm3. We detect activation in subcortical, thalamic, and extended temporal structures, conforming to known anatomical and functional brain networks associated with the respective sites of stimulation. This demonstrates that high-resolution localization of experimentally produced deep sources is possible within an intact brain. This approach is suitable for exploring causal relationships between discrete brain regions through precise optogenetic control and simultaneous whole brain MEG recording with high-resolution magnetic source imaging (MSI).