Function In Clinical Populations Research Articles

B - 122 A Preliminary Analysis of the Neuropsychological Evaluation of the UPSA (NEUPSA)

Abstract Objective The UCSD Performance Skills Assessment (UPSA) is a well-established performance instrument created to evaluate functional outcomes. We applied a neuropsychological framework to the UPSA and created the Neuropsychological Evaluation of the UPSA (NEUPSA), assessing the cognitive processes that underlie the functional tasks in the UPSA. The study aimed to compare the executive function and attention components of the NEUPSA with a validated computerized cognitive assessment. Methods Participants were 86 adults drawn from the San Diego community. Participants completed the UPSA, 5 Choice CPT (5CCPT) which evaluates attention by calculating a d-prime score that assesses sustained attention, and the Iowa Gambling Task (IGT) which assesses risky decision making. We employed a Spearman’s correlation analysis with a 95% confidence interval to assess the strength of the relationship between NEUPSA attention scores and 5CCPT and IGT performance. Results NEUPSA subscores were significantly correlated with performance on computerized cognitive assessments. 5CCPT scores were positively correlated with NEUPSA attention scores (r = 0.24, p = 0.03). IGT scores were positively correlated with NEUPSA executive functioning scores (r = 0.23, p = 0.04). Conclusion These findings provide preliminary evidence that the NEUPSA assesses aspects of attention (i.e., sustained attention) and executive function (i.e., risky decision making). Further research, however, needs to be conducted on the validity of this measure and the utility in assessing neuropsychological function in clinical populations. Next steps include assessing NEUPSA performance in various non-healthy comparison populations. In this study, we emphasize the fundamental cognitive principles necessary for performance, offering a promising avenue for comprehending impaired functioning.

Motoneuron persistent inward current contribution to increased torque responses to wide-pulse high-frequency neuromuscular electrical stimulation

PurposeTo assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra torque, progressive increase in torque during stimulation, and estimates of the persistent inward current (PIC) contribution to motoneuron firing in the plantar flexors.MethodsTen participants performed triangular shaped contractions to 20% of maximal plantar flexion torque before and after WPHF NMES with and without a handgrip contraction, and control conditions. Extra torque, the relative difference between the initial and final torque during stimulation, and sustained electromyographic (EMG) activity were assessed. High-density EMG was recorded during triangular shaped contractions to calculate ∆F, an estimate of PIC contribution to motoneuron firing, and its variation before vs after the intervention referred to as ∆F change score.ResultsWhile extra torque was not significantly increased with remote contraction (WPHF + remote) vs WPHF (+ 37 ± 63%, p = 0.112), sustained EMG activity was higher in this condition than WPHF (+ 3.9 ± 4.3% MVC EMG, p = 0.017). Moreover, ∆F was greater (+ 0.35 ± 0.30 Hz) with WPHF + remote than control (+ 0.03 ± 0.1 Hz, p = 0.028). A positive correlation was found between ∆F change score and extra torque in the WPHF + remote (r = 0.862, p = 0.006).DiscussionThe findings suggest that the addition of remote muscle contraction to WPHF NMES enhances the central contribution to torque production, which may be related to an increased PIC contribution to motoneuron firing. Gaining a better understanding of these mechanisms should enable NMES intervention optimization in clinical and rehabilitation settings, improving neuromuscular function in clinical populations.

Extending the PROMIS item bank “ability to participate in social roles and activities”: a psychometric evaluation using IRT

ObjectiveOur objective was to explore whether the extension of the PROMIS item bank Ability to Participate in Social Roles and Activities (APSRA) with new items would result in more effective targeting (i.e., selecting items that are appropriate for each individual's trait level), and more reliable measurements across all latent trait levels.MethodsA sample of 1,022 Dutch adults completed all 35 items of the original item bank plus 17 new items (in Dutch). The new items presented in this publication have been translated provisionally from Dutch into English for presentation purposes. We evaluated the basic IRT assumptions unidimensionality, local independence, and monotonicity. Furthermore, we examined the item parameters, and assessed differential item functioning (DIF) for sex, education, region, age, and ethnicity. In addition, we compared the test information functions, item parameters, and θ scores, for the original and extended item bank in order to assess whether the measurement range had improved.ResultsWe found that the extended item bank was compatible with the basic IRT assumptions and showed good reliability. Moreover, the extended item bank improved the measurement in the lower trait range, which is important for reliably assessing functioning in clinical populations (i.e., persons reporting lower levels of participation).ConclusionWe extended the PROMIS-APSRA item bank and improved its psychometric quality. Our study contributes to PROMIS measurement innovation, which allows for the addition of new items to existing item banks, without changing the interpretation of the scores and while maintaining the comparability of the scores with other PROMIS instruments.

Abstract 6290: Effects of a circuit, interval-based exercise program on vascular function among cancer survivors

Abstract Background: Cancer survivors are at an increased risk of cardiovascular comorbidity, including atherosclerosis, hypertension, and heart failure, due to negative impacts of cancer treatments on vascular function. Exercise is recommended in recent cardio-oncology rehabilitation guidelines and has been shown to improve vascular function in clinical populations; however, its effects on vascular function are understudied in clinical oncology settings. Purpose: This pilot study examined whether a circuit, interval-based exercise intervention can improve vascular function, assessed by brachial artery flow-mediated dilation (baFMD) and carotid intima media thickness (cIMT) in breast, prostate, and colorectal cancer survivors. Methods: Overweight or obese (BMI>25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors were randomized to exercise (n=60) or usual care (n=30). Survivors in the 4-month exercise intervention trained three times/week, in a circuit, interval-based supervised moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) program. cIMT and baFMD were measured at baseline and post-intervention via an ultrasound. Paired t-tests and repeated-measures analysis of variance were run to assess within- and between-group differences. Results: The study sample included breast (n=38), prostate (n=24), colorectal (n=28) cancer survivors who were 63.2 ± 10.8 years old, completed chemotherapy and/or radiation (75%) and were obese (87%). Post-intervention, baFMD significantly increased in the exercise group compared to the control group (between-group mean difference: 6.3%; 95% CI: [1.9 to 9.3], p=0.001). There was also a significant reduction in cIMT in the exercise group compared to the control group (between-group mean difference: -0.039mm, 95% CI: [-0.080 to -0.009], p=0.002). Conclusions: Our findings in this pilot study support that a circuit, interval-based aerobic and resistance exercise intervention may improve vascular function in breast, prostate, and colorectal cancer survivors. Future studies are recommended to understand how exercise interventions can be utilized clinically to improve cardiovascular disease risk and co-morbidity among cancer survivors. Citation Format: Cami N. Christopher, Dong-Woo Kang, Paola Gonzalo-Encabo, Rebekah L. Wilson, Amber J. Normann, Mary K. Norris, Christina M. Dieli-Conwright. Effects of a circuit, interval-based exercise program on vascular function among cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6290.

Using immersive virtual reality to remotely examine performance differences between dominant and non-dominant hands

Circle drawing may be a useful task to study upper-limb function in patient populations. However, previous studies rely on expensive and bulky robotics to measure performance. For clinics or hospitals with limited budgets and space, this may be unfeasible. Virtual reality (VR) provides a portable and low-cost tool with integrated motion capture. It offers potentially a more feasible medium by which to assess upper-limb motor function. Prior to use with patient populations, it is important to validate and test the capabilities of VR with healthy users. This study examined whether a VR-based circle drawing task, completed remotely using participant’s own devices, could capture differences between movement kinematics of the dominant and non-dominant hands in healthy individuals. Participants (n = 47) traced the outline of a circle presented on their VR head-mounted displays with each hand, while the positions of the hand-held controllers were continuously recorded. Although there were no differences observed in the size or roundness of circles drawn with each hand, consistent with prior literature our results did show that the circles drawn with the dominant hand were completed faster than those with the non-dominant hand. This provides preliminary evidence that a VR-based circle drawing task may be a feasible method for detecting subtle differences in function in clinical populations.

Deconstructing the functional significance of the error-related negativity (ERN) and midline frontal theta oscillations using stepwise time-locking and single-trial response dynamics

Error-related electroencephalographic potentials have been used for decades to develop theoretical models of response monitoring processes, study altered cognitive functioning in clinical populations, and more recently, to improve the performance of brain-computer interfaces. However, the vast majority of this research relies on discrete behavioral responses that confound error detection, response cancelation, error correction, and post-error cognitive and affective processes. By contrast, the present study demonstrates a novel, complementary method for isolating the functional correlates of error-related electroencephalographic responses using single-trial kinematic analyses of cursor trajectories and a stepwise time-locking analysis. The results reveal that the latency of the ERN, Pe, and medial-frontal theta oscillations are all strongly positively correlated with the latency at which an initiated error response is canceled, as indicated by the peak deceleration of the initiated movement prior to a corrective response. Results are discussed with respect to current theoretical models of error-related brain potentials and potential relevance to clinical applications.

RGB-Depth Camera-Based Assessment of Motor Capacity: Normative Data for Six Standardized Motor Tasks.

Instrumental motion analysis constitutes a promising development in the assessment of motor function in clinical populations affected by movement disorders. To foster implementation and facilitate interpretation of respective outcomes, we aimed to establish normative data of healthy subjects for a markerless RGB-Depth camera-based motion analysis system and to illustrate their use. We recorded 133 healthy adults (56% female) aged 20 to 60 years with an RGB-Depth camera-based motion analysis system. Forty-three spatiotemporal parameters were extracted from six short, standardized motor tasks-including three gait tasks, stepping in place, standing-up and sitting down, and a postural control task. Associations with confounding factors, height, weight, age, and sex were modelled using a predictive linear regression approach. A z-score normalization approach was provided to improve usability of the data. We reported descriptive statistics for each spatiotemporal parameter (mean, standard deviation, coefficient of variation, quartiles). Robust confounding associations emerged for step length and step width in comfortable speed gait only. Accessible normative data usage was lastly exemplified with recordings from one randomly selected individual with multiple sclerosis. We provided normative data for an RGB depth camera-based motion analysis system covering broad aspects of motor capacity.

Cortical theta-gamma coupling governs the adaptive control of motor commands.

Motor control requires the adaptive updating of internal models to successfully target desired outcomes. This adaptive control can be proactive, such that imminent actions and corresponding sensorimotor programmes are anticipated prior to movement, or reactive, such that online error correction is necessary to adjust to sudden changes. While substantial evidence implicates a distributed cortical network serving adaptive control when behavioural changes are required (e.g. response inhibition), the neural dynamics serving such control when the target motor commands are to remain intact are poorly understood. To address this, we developed a novel proactive-reactive cued finger tapping paradigm that was performed during magnetoencephalography by 25 healthy adults. Importantly, to ensure condition-wise differences in adaptive cueing were not attributable to changes in movement kinematics, motor selection and planning processes were held constant despite changes in task demands. All data were imaged in the time-frequency domain using a beamformer to evaluate the effect of proactive and reactive cues on movement-related oscillations and subsequent performance. Our results indicated spectrally specific increases in low (i.e. theta) and high (i.e. gamma) frequency oscillations during motor execution as a function of adaptive cueing. Additionally, we observed robust cross-frequency coupling of theta and gamma oscillatory power in the contralateral motor cortex and further, the strength of this theta-gamma coupling during motor execution was differentially predictive of behavioural improvements and decrements during reactive and proactive trials, respectively. These data indicate that functional oscillatory coupling may govern the adaptive control of movement in the healthy brain and importantly, may serve as effective proxies for characterizing declines in motor function in clinical populations in the future.

Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial.

Regular exercise and sauna bathing have each been shown to improve cardiovascular function in clinical populations. However, experimental data on the cardiovascular adaptations to regular exercise in conjunction with sauna bathing in the general population are lacking. Therefore, we compared the effects of exercise and sauna bathing to regular exercise using a multi-arm randomized controlled trial. Participants (n = 47) aged 49 ± 9 with low physical activity levels and at least one traditional cardiovascular disease (CVD) risk factor were randomly assigned (1:1:1) to guideline-based regular exercise and 15-min postexercise sauna (EXS), guideline-based regular exercise (EXE), or control (CON) for 8 wk. The primary outcomes were blood pressure (BP) and cardiorespiratory fitness (CRF). Secondary outcomes included fat mass, total cholesterol levels, and arterial stiffness. EXE had a greater change in CRF (+6.2 mL/kg/min; 95% CI, +4.2 to +8.3 mL/kg/min) and fat mass but no differences in BP when compared with CON. EXS displayed greater change in CRF (+2.7 mL/kg/min; 95% CI, +0.2 to +5.3 mL/kg/min), lower systolic BP (-8.0 mmHg; 95% CI, -14.6 to -1.4 mmHg), and lower total cholesterol levels compared with EXE. Regular exercise improved CRF and body composition in sedentary adults with CVD risk factors. However, when combined with exercise, sauna bathing demonstrated a substantially supplementary effect on CRF, systolic BP, and total cholesterol levels. Sauna bathing is a valuable lifestyle tool that complements exercise for improving CRF and decreasing systolic BP. Future research should focus on the duration and frequency of exposure to ascertain the dose-response relationship.

An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise-Induced Human Skeletal Muscle Hypertrophy.

ABSTRACTSkeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)–induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle–derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.

Effects of exercise intensity on gut microbiome composition and function in people with type 2 diabetes

ABSTRACT Exercise is positively associated with higher microbial diversity, but there is limited information on exercise intensity's effect on gut microbiome composition and function in clinical populations. This study examines whether different intensities of exercise exert differential effects on gut microbiome composition and function in low active people with type 2 diabetes. This is a sub-study of the Exercise for Type 2 Diabetes Study, a single centre, prospective, randomised controlled trial. Participants (n = 12) completed 8-weeks of combined aerobic and resistance moderate intensity continuous training (C-MICT) or combined aerobic and resistance high-intensity interval training (C-HIIT). Faecal samples were collected before and after intervention to measure gut microbiome composition and metabolic pathways (metagenome shotgun sequencing) and short-chain fatty acids. Post-exercise α-diversity was different between groups as was the relative abundance of specific taxa was (p < .05). Post-exercise relative abundance of Bifidobacterium, A. municiphila, and butyrate-producers Lachnospira eligens, Enterococcus spp., and Clostridium Cluster IV were higher at lower exercise intensity. Other butyrate-producers (from Eryspelothrichales and Oscillospirales), and methane producer Methanobrevibacter smithii were higher at higher exercise intensity. Pyruvate metabolism (ko00620),COG “Cell wall membrane envelope biogenesis” and “Unknown function” pathways were significantly different between groups and higher in C-MICT post-exercise. Differential abundance analysis on KO showed higher expression of Two-component system in C-HIIT. Transcription factors and “unknown metabolism” related pathways decreased in both groups. There were no significant between group changes in faecal short chain fatty acids. Exercise intensity had a distinct effect on gut microbiome abundance and metabolic function, without impacting short-chain fatty acid output. Highlights Evidence of exercise effect on gut microbiome outcomes is limited to healthy and athletic populations In low active people with type 2 diabetes, different exercise intensities increased specific health promoting and butyrate producers species, and showed differentially abundant gut microbiome metabolic pathways. Further investigation is warranted, and if this supports the present findings, then specific exercise intensities may be promoted to target specific species and optimise gut health.

A Tailored Music-Motor Therapy and Real-Time Biofeedback Mobile Phone App ('GotRhythm') to Promote Rehabilitation Following Stroke: A Pilot Study.

Background:Stroke persists as an important cause of long-term disability world-wide with the need for rehabilitation strategies to facilitate plasticity and improve motor function in stroke survivors. Rhythm-based interventions can improve motor function in clinical populations. This study tested a novel music-motor software application ‘GotRhythm’ on motor function after stroke.Methods:Participants were 22 stroke survivors undergoing inpatient rehabilitation in a subacute stroke ward. Participants were randomised to the GotRhythm intervention (combining individualised music and augmented auditory feedback along with wearable sensors to deliver a personalised rhythmic auditory stimulation training protocol) or usual care. Intervention group participants were offered 6-weeks of the GotRhythm intervention, consisting of a supervised 20-minute music-motor therapy session using GotRhythm conducted 3 times a week for 6 weeks. The primary feasibility outcomes were adherence to the intervention and physical function (change in the Fugl-Meyer Assessment of Motor Recovery score) measured at baseline, after 3-weeks and at end of the intervention period (6-weeks).Results:Three of 10 participants randomised to the intervention did not receive any of the GotRhythym music-motor therapy. Of the remaining 7 intervention group participants, only 5 completed the 3-week mid-intervention assessment and only 2 completed the 6-week post-intervention assessment. Participants who used the intervention completed 5 (IQR 4,7) sessions with total ‘dose’ of the intervention of 70 (40, 201) minutes.Conclusion:Overall, adherence to the intervention was poor, highlighting that application of technology assisted music-based interventions for stroke survivors in clinical environments is challenging along with usual care, recovery, and the additional clinical load.

Frequency and characteristics of falls in people living with and without multiple sclerosis during the COVID-19 pandemic: A cross-sectional online survey

BackgroundPublic health responses to Coronavirus Disease 2019 (COVID-19) including lockdowns may negatively impact physical and mental functioning in clinical populations. People living with multiple sclerosis (MS) may be more susceptible to physical function deterioration while practicing social distancing. Recent reports have suggested that about 50% of people with MS (pwMS) decreased their leisure physical activity during COVID-19, and upwards of 30% reported decreased physical fitness levels. However, the impact of social distancing on adverse health-related outcomes such as falls has not received much scrutiny. Therefore, we explored the frequency and characteristics of falls experienced by people living with and without MS during the COVID-19 pandemic. MethodsTwo-hundred and thirty-nine individuals, including 106 pwMS (median age: 59 years) and 133 people living without MS (median age: 66 years) were recruited for this cross-sectional study. A snowball sampling strategy was used for online recruitment. Participants completed a customized falls questionnaire and the number of falls experienced (if any) during COVID-19 was recorded. Fall-related characteristics such as the timing, locations, activities undertaken before falling and consequences, as well as self-reported physical activity were also recorded. ResultsOverall, participants reported 232 falls (1.67 falls/person in pwMS and 0.41 falls/person in non-MS participants). People living with MS (pwMS) had a significantly higher frequency of falls (58.5% vs 21.8%; p< 0.001) and recurrent falls (45.3% vs 9.8%; p< 0.001) compared to non-MS participants. Additionally, pwMS reported a significantly higher proportion of in-home falls (83.9% vs 54.2%; p = 0.004), as well as a higher proportion of overall injuries (44.3% vs 12.5%, p< 0.001), fractures (5.7% vs 0.8%, p = 0.048), and healthcare utilization (9.4% vs 1.6%, p = 0.007) compared to non-MS participants. A similar proportion of pwMS (49.1%) and non-MS participants (52.2%) reported lower physical activity levels during COVID-19. ConclusionThis cross-sectional study revealed that pwMS remain at high risk of falls and fall-related outcomes during COVID-19. The high number of falls experienced by pwMS is of clinical concern considering the current strain on the healthcare system. Findings from this study highlight the importance of monitoring falls and the potential for telerehabilitation in persons with MS during COVID-19.

Myocellular Adaptations to Low-Load Blood Flow Restricted Resistance Training.

Low-load blood flow restricted resistance exercise (BFRRE) can stimulate whole-muscle growth and improve muscle function. However, limited knowledge exists on the effects at the myocellular level. We hypothesize that BFRRE has the ability to produce concurrent skeletal muscle myofibrillar, mitochondrial, and microvascular adaptations, thus offering an alternative strategy to counteract decay in skeletal muscle health and function in clinical populations.

Exercise With Blood Flow Restriction To Improve Muscular And Physical Function After Total Knee Arthroplasty

After a total knee arthroplasty (TKA), quadriceps strength and physical function can be impaired for several years. Blood flow restriction (BFR) exercise is an effective method to improve muscular and physical function in clinical populations with knee joint pathologies. To date, there are two case studies documenting application of BFR after TKA. A next step is to determine the feasibility of BFR in a larger TKA cohort. PURPOSE: To evaluate the effectiveness of a 10wk home-based BFR exercise program to improve muscular and physical function after TKA. METHODS: Six adults (age: 59±9yrs, BMI: 33±5) with a unilateral TKA (2.7±1.7yrs post-surgery) performed body weight half squats, isolated knee extension using a resistance band, and walking exercises with BFR 3x/wk for 10wk. During exercise, blood flow in the affected limb was restricted using a 15cm wide thigh cuff inflated to 50% of limb occlusion pressure which was identified using Doppler ultrasound. Outcome measures of vastus lateralis thickness, maximal knee extensor isometric torque, and physical function (repetitions performed during 30s chair stand test, distance covered during 6min walk test) were assessed at baseline and post-training. RESULTS: Participants completed 98% of the home-based BFR training sessions and tolerated the exercise program well as joint pain (0.6±0.1cm) and muscle soreness (0.5±0.1cm) were very low (0-10cm visual analogue scale). Vastus lateralis thickness and knee extensor strength in the affected leg increased by 18±11% and 17±13%, respectively (both P<0.05). After training, number of repetitions during the 30s chair stand test increased (11±2 vs. 18±4 repetitions, p<0.01) and this change (6 repetitions) exceeded the minimally important clinical difference. There was a significant increase in distance covered during the 6min walk test (511±28 vs. 556±36m, 9±7%, p=0.03) but this improvement (46m) did not exceed the clinical threshold. CONCLUSION: Results from this pilot study are promising and suggest that home-based BFR exercise can be feasible, safe, and effective for improving muscular and physical function after TKA. Further research is needed to confirm these initial findings in a larger randomized TKA control trial.

Dietary nitrate improves skeletal muscle microvascular oxygenation in HIV-infected patients receiving highly active antiretroviral therapy: a randomised, double-blind, cross-over, placebo-controlled study.

HIV-1 proteins and highly active antiretroviral therapy (HAART) have been associated with microvascular endothelial dysfunction. Although nitrate-rich beetroot juice (NR-BJ) consumption has been shown to improve endothelial function in clinical population, its effects in HIV-infected patients has not been addressed. We investigated the effect of a single dose of NR-BJ on muscle oxygen saturation parameters in response to a handgrip exercise in HIV-infected patients. Fifteen HIV-infected patients received NR-BJ or nitrate-depleted beetroot juice (ND-BJ) in a double-blind cross-over design. Near-IR spectroscopy was utilised to assess muscle oxygen saturation parameters during rhythmic handgrip exercise after NR-BJ or ND-BJ supplementation. A significant faster muscle oxygen desaturation rate during exercise (-7·97 (sd 5·00) v. -5·45 (3·94) %/s, P = 0·005) and muscle oxygen resaturation rate during exercise recovery (0·43 (0·24) v. 0·28 (0·24) %/s, P = 0·030) after NR-BJ ingestion was found. However, no significant difference in exercise time until fatigue was observed. Salivary nitrite and urinary nitrate concentration were analysed after NR-BJ or ND-BJ. A significant increase in salivary nitrite and urinary nitrate in NR-BJ was observed compared with ND-BJ (P < 0·05). Our findings suggest that NR-BJ consumption may acutely improve muscle oxygen saturation during exercise and exercise recovery in HIV-infected patients undergoing HAART and who are expected to present microvascular damage. Thus, future studies investigating the chronic effects of NR-BJ are warranted to delineate a better nutritional strategy based on nitrate-rich foods.

Salivary Alpha-Amylase as a Biomarker of Stress in Behavioral Medicine

In recent years, research in behavioral medicine has become increasingly focused on understanding how chronic and acute exposure to stress impacts health outcomes. During stress, the body’s physiological stress systems are activated. These systems closely interact with the immune system and are, thus, importantly implicated in the onset and maintenance of disease states. While much of the research in behavioral medicine that has investigated the effects of stress on disease has focused on the role of the hypothalamic-pituitary-adrenal axis and its downstream biomarker, cortisol, it is evident that the autonomic nervous system (ANS) also plays a crucial role in both the biological stress process and the manifestation and maintenance of stress-related symptoms. In recent years salivary alpha-amylase (sAA) has emerged as a valid and reliable marker of ANS activity in stress research and is therefore an important biomarker to consider in behavioral medicine. In this commentary, we will highlight research relevant for behavioral medicine that has utilized sAA measurements, both basally, and in response to stress, to examine ANS function in clinical populations. We will additionally summarize findings from studies that have examined the effects of various targeted interventions on changes in sAA levels. Through this, our aim is to present evidence that sAA can serve as a feasible biomarker of ANS (dys)function in health and disease. To this end, we will also highlight important methodological considerations for readers to keep in mind when including sAA assessments in their own studies. The overarching goal of this brief commentary is to highlight how a multidimensional approach toward physiological stress measurement can allow researchers to develop a better understanding of physical health and disease states.

Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males.

Purpose: High-load resistance exercise contributes to maintenance of muscle mass, muscle protein quality, and contractile function by stimulation of muscle protein synthesis (MPS), hypertrophy, and strength gains. However, high loading may not be feasible in several clinical populations. Low-load blood flow restricted resistance exercise (BFRRE) may provide an alternative approach. However, the long-term protein synthetic response to BFRRE is unknown and the myocellular adaptations to prolonged BFRRE are not well described.Methods: To investigate this, 34 healthy young subjects were randomized to 6 weeks of low-load BFRRE, HLRE, or non-exercise control (CON). Deuterium oxide (D2O) was orally administered throughout the intervention period. Muscle biopsies from m. vastus lateralis were collected before and after the 6-week intervention period to assess long-term myofibrillar MPS and RNA synthesis as well as muscle fiber-type-specific cross-sectional area (CSA), satellite cell content, and myonuclei content. Muscle biopsies were also collected in the immediate hours following single-bout exercise to assess signaling for muscle protein degradation. Isometric and dynamic quadriceps muscle strength was evaluated before and after the intervention.Results: Myofibrillar MPS was higher in BFRRE (1.34%/day, p < 0.01) and HLRE (1.12%/day, p < 0.05) compared to CON (0.96%/day) with no significant differences between exercise groups. Muscle RNA synthesis was higher in BFRRE (0.65%/day, p < 0.001) and HLRE (0.55%/day, p < 0.01) compared to CON (0.38%/day) and both training groups increased RNA content, indicating ribosomal biogenesis in response to exercise. BFRRE and HLRE both activated muscle degradation signaling. Muscle strength increased 6–10% in BFRRE (p < 0.05) and 13–23% in HLRE (p < 0.01). Dynamic muscle strength increased to a greater extent in HLRE (p < 0.05). No changes in type I and type II muscle fiber-type-specific CSA, satellite cell content, or myonuclei content were observed.Conclusions: These results demonstrate that BFRRE increases long-term muscle protein turnover, ribosomal biogenesis, and muscle strength to a similar degree as HLRE. These findings emphasize the potential application of low-load BFRRE to stimulate muscle protein turnover and increase muscle function in clinical populations where high loading is untenable.

Imaging Habenula Volume in Schizophrenia and Bipolar Disorder.

The habenula (Hb), a bilateral nucleus located next to the dorsomedial thalamus, is of particular relevance to psychiatric disorders based on preclinical evidence linking the Hb to depressive and amotivational states. However, studies in clinical samples are scant because segmentation of the Hb in neuroimaging data is challenging due to its small size and low contrast from the surrounding tissues. Negative affective states dominate the clinical course of schizophrenia and bipolar disorder and represent a major cause of disability. Diagnosis-related alterations in the volume of Hb in these disorders have therefore been hypothesized but remain largely untested. To probe this question, we used a recently developed objective and reliable semi-automated Hb segmentation method based on myelin-sensitive magnetic resonance imaging (MRI) data. We ascertained case-control differences in Hb volume from high resolution structural MRI data obtained from patients with schizophrenia (n = 95), bipolar disorder (n = 44) and demographically matched healthy individuals (n = 52). Following strict quality control of the MRI data, the final sample comprised 68 patients with schizophrenia, 32 with bipolar disorder and 40 healthy individuals. Regardless of diagnosis, age, sex, and IQ were not correlated with Hb volume. This was also the case for age of illness onset and medication (i.e., antipsychotic dose and lithium-treatment status). Case-control differences in Hb volume did not reach statistical significance; their effect size (Cohen's d) was negligible on the left (schizophrenia: 0.14; bipolar disorder: −0.03) and small on the right (schizophrenia: 0.34; bipolar disorder: 0.26). Nevertheless, variability in the volume of the right Hb was associated with suicidality in the entire patient sample (ρ = 0.29, p = 0.004) as well as in each patient group (bipolar disorder: ρ = 0.34, p = 0.04; schizophrenia: ρ = 0.25, p = 0.04). These findings warrant replication in larger samples and longitudinal designs and encourage more comprehensive characterization of Hb connectivity and function in clinical populations.

DIFFUSE INTERSTITIAL MYOCARDIAL FIBROSIS IS ASSOCIATED WITH ABNORMAL LEFT ATRIAL MECHANICS

An increasing number of studies demonstrate the clinical and prognostic importance of phasic LA function. A better understanding of the determinants of LA function in clinical populations is required. Increased myocardial stiffness from myocardial fibrosis may impair afterload during LA contraction