Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells.

Most prostate cancers express the androgen receptor (AR), and tumor growth and progression are facilitated by exceptionally low levels of systemic or intratumorally produced androgens. Thus, absolute inhibition of the androgen signaling axis remains the goal of current therapeutic approaches to treat prostate cancer (PCa). Paradoxically, high dose androgens also exhibit considerable efficacy as a treatment modality in patients with late-stage metastatic PCa. Here we show that low levels of androgens, functioning through an AR monomer, facilitate a non-genomic activation of the mTOR signaling pathway to drive proliferation. Conversely, high dose androgens facilitate the formation of AR dimers/oligomers to suppress c-MYC expression, inhibit proliferation and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR action in PCa and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies.

Short-latency afferent inhibition and its relationship to covert sensory and motor hand impairment in multiple sclerosis.

OBJECTIVE: To investigate sensorimotor integration by quantifying short-latency afferent inhibition (SAI) in people with MS who experience manual dexterity problems compared to controls. METHODS: 22 people with MS with self-reported manual dexterity problems and 10 sex and age-matched controls were assessed using various upper extremity clinical tests. SAI was assessed by a transcranial magnetic stimulation pulse over the primary motor cortex preceded by peripheral nerve stimulation to the median nerve at 6 interstimulus intervals 2 - 8 ms longer than individualized N20 latencies. RESULTS: Although within normal limits, persons with MS exhibited significantly slower Nine Hole Peg Test performance and pinch strength in the dominant hand. They also exhibited greater sensory impairment (monofilament test) in the dominant hand. Persons with MS showed significantly greater disinhibition of SAI in the dominant hand compared to controls, which was significantly correlated with weaker pinch strength. CONCLUSION: Reduced SAI in people with MS, particularly in the dominant hand, signifies disruptions in cortical cholinergic inhibitory activity and is associated with lower pinch strength. SIGNIFICANCE: Evaluating changes in SAI may offer insight into the disrupted cortical cholinergic inhibitory activity that contributes to sensorimotor disintegration, potentially advancing disease management in persons with MS.

Persistent hyperbilirubinemia following preoperative biliary stenting in patients undergoing anatomic hepatectomy predicts serious complications.

BACKGROUND: Biliary obstruction before liver resection is a known risk factor for post-operative complications. The aim of this study was to determine the impact of persistent hyperbilirubinemia following preoperative biliary drainage before liver resection. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients with cholangiocarcinoma who underwent anatomic liver resection with preoperative biliary drainage comparing those with persistent hyperbilirubinemia (> 1.2 mg/dL) to those with resolution. Patient characteristics and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including persistent hyperbilirubinemia to evaluate their independent effect on serious complications, liver failure, and mortality. RESULTS: We evaluated 463 patients with 217 (46.9%) having hyperbilirubinemia (HB) despite biliary stenting. Bivariate analysis demonstrated that patients with HB had a higher rate of serious complications than those with non-HB (80.7% vs 70.3%; P = 0.010) including bile leak (40.9% vs 31.8%; P = 0.045), liver failure (26.7% vs 17.9%; P = 0.022), and bleeding (48.4% vs 36.6%; P = 0.010). Multivariable analysis demonstrated that persistent HB was independently associated with serious complications (OR 1.88, P = 0.020) and mortality (OR 2.39, P = 0.049) but not post-operative liver failure (OR 1.65, P = 0.082). CONCLUSIONS: Failed preoperative biliary decompression is a predictive factor for post-operative complications and mortality in patients undergoing hepatectomy and may be useful for preoperative risk stratification.

Oral care reduces incidence of pneumonia after esophagectomy: systematic review and meta-analysis.

PURPOSE: Post-operative pneumonia after esophagectomy is a major contributor to morbidity and mortality. Prior studies have demonstrated a link between the presence of pathologic oral flora and the development of aspiration pneumonia. The objective of this systematic review and meta-analysis was to evaluate the effect of pre-operative oral care on the incidence of post-operative pneumonia after esophagectomy. METHODS: A systematic search of the literature was performed on September 2, 2022. Screening of titles and abstracts, full-text articles, and evaluation of methodological quality was performed by two authors. Case reports, conference proceedings, and animal studies were excluded. A meta-analysis of peri-operative oral care on the odds of post-operative pneumonia after esophagectomy was performed using Revman 5.4.1 with a Mantel-Haenszel, random-effects model. RESULTS: A total of 736 records underwent title and abstract screening, leading to 28 full-text studies evaluated for eligibility. A total of nine studies met the inclusion criteria and underwent meta-analysis. Meta-analysis revealed a significant reduction in post-operative pneumonia among patients undergoing pre-operative oral care intervention compared to those without an oral care intervention (OR 0.57, 95% CI 0.43-0.74, p < 0.0001; I2 = 49%). CONCLUSION: Pre-operative oral care interventions have significant potential in the reduction of post-operative pneumonia after esophagectomy. North American prospective studies, as well as studies on the cost-benefit analysis, are required.

Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review.

BACKGROUND: Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose. OBJECTIVES: To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS. METHODS: We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain). RESULTS: The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability. DISCUSSION: TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes.

Better cognitive function predicts maintenance of dual-task walking ability over time among people with relapsing-remitting MS.

OBJECTIVE: Physical fitness and preserved cognitive function may provide neuroprotection in multiple sclerosis (MS), but few studies have examined their role in symptom progression over time. Dual-task paradigms can be useful to detect subtle impairment among people with MS in early stages of the disease. The present study investigated whether higher aerobic fitness or greater cognitive function could predict performance in dual-task walking 1-2 years later among people with mild or no MS-related walking impairment. METHOD: Participants (n = 50) performed dual-task walking (walking while serially subtracting 7's from 100), completed the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and a fitness test (VO2max). They were tested at two time points (T1 and T2), approximately 1 year apart. Walking speed, MoCA, SDMT, and VO2max at baseline (T1) were examined as predictors of dual-task walking speed at T2. RESULTS: MoCA (higher score), but not SDMT or fitness, was significantly correlated with percentage decrease in dual-task walking and was a significant predictor of dual-task-walking speed at T2, accounting for additional 6.1% of its variance. Cognitive impairment (MoCA < 26) at baseline corresponded to a 12 cm/s unit decrease in dual-task-walking speed at T2. CONCLUSIONS: Our results provide longitudinal evidence that better cognitive function, specifically global MoCA score, may protect against decline in dual-task walking ability over the years. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Bipedal hopping as a new measure to detect subtle sensorimotor impairment in people with multiple sclerosis.

BACKGROUND: Bipedal hopping has the potential to detect subtle multiple sclerosis (MS)-related impairments, especially among patients who "pass" typical movement tests. In this narrative review, we outline the biomechanics of bipedal hopping and propose its usefulness as a novel outcome measure for people with MS having mild disability. METHODS: We summarize articles that (1) examined the biomechanics of jumping or hopping and (2) tested the validity and/or reliability of hopping tests. We consolidated consistencies and gaps in research and opportunities for future development of the bipedal hop test. RESULTS: Bipedal hopping requires immense power, coordination, balance, and ability to reduce co-contraction; movement components typically affected by MS. These impairments can be measured and differentiated by examining specific variables, such as hop length (power), symmetry (coordination), center of pressure (balance), and coefficient of variability (co-contraction/spasticity). Bipedal hopping challenges these aspects of movement and exposes sensorimotor impairments that may not have been apparent during walking. CONCLUSIONS: Testing of bipedal hopping on an instrumented walkway may detect and monitor sensorimotor control in people with MS who do not currently present with clinical deficits. Early measurement is imperative for precise rehabilitation prescription to slow disability progression prior to onset of measurable gait impairment.Implications for rehabilitationJumping and hopping tests detect lower limb and balance impairments in children, athletes, and older adults.Bipedal hop test measures multiple domains: power, coordination, balance, and muscle timing.Bipedal hop test may expose subtle sensorimotor impairments in people with multiple sclerosis.Multiple variables measured can discern type of sensorimotor impairment to direct personalized rehabilitation programs.

Spatiotemporal Gait Measurement With a Side-View Depth Sensor Using Human Joint Proposals.

We propose a method for calculating standard spatiotemporal gait parameters from individual human joints with a side-view depth sensor. Clinical walking trials were measured concurrently by a side-view Kinect and a pressure-sensitive walkway, the Zeno Walkway. Multiple joint proposals were generated from depth images by a stochastic predictor based on the Kinect algorithm. The proposals are represented as vertices in a weighted graph, where the weights depend on the expected and measured lengths between body parts. A shortest path through the graph is a set of joints from head to foot. Accurate foot positions are selected by comparing pairs of shortest paths. Stance phases of the feet are detected by examining the motion of the feet over time. The stance phases are used to calculate four gait parameters: stride length, step length, stride width, and stance percentage. A constant frame rate was assumed for the calculation of stance percentage because time stamps were not captured during the experiment. Gait parameters from 52 trials were compared to the ground truth walkway using Bland-Altman analysis and intraclass correlation coefficients. The large spatial parameters had the strongest agreements with the walkway (ICC(2, 1) = 1.00 and 0.98 for stride and step length with normal pace, respectively). The presented system directly calculates gait parameters from individual foot positions while previous side-view systems relied on indirect measures. Using a side-view system allows for tracking walking in both directions with one camera, extending the range in which the subject is in the field of view.

Perspectives of People with Multiple Sclerosis About Helminth Immunotherapy.

BACKGROUND: Due to the chronic and incurable nature of the autoimmune disease multiple sclerosis (MS), some people with MS will seek out alternative therapeutic approaches. Helminth immunotherapy, the deliberate inoculation with helminthic parasites as an intervention to prevent, delay, or minimize progression of autoimmune disorders, is one such approach gaining traction in academic research and with the public. Herein, we explored the perspectives of people with MS regarding helminth immunotherapy and its use in disease management. METHODS: Interpretive description, a qualitative research approach, was applied to data extracted from online forums. Multiple investigators independently identified, extracted, and analyzed data to develop preliminary codes. Inductive thematic analysis and triangulation were then used to collaboratively establish themes. RESULTS: Four main themes were generated: experience of living with MS, influential factors in contemplating helminth immunotherapy, logistics of helminth immunotherapy, and concerns about helminth immunotherapy. CONCLUSIONS: There was a general consensus in publicly available online forums that conventional therapies do not provide meaningful improvement for some people with MS. These people may seek alternative therapies such as helminth immunotherapy. Information on helminth immunotherapy from internet resources (eg, blogs and social media forums) can contain biased and scientifically unsupported opinions. Messages of efficacy and improved quality of life are readily available and may influence people with MS considering helminth immunotherapy as an alternative therapy. Although some people with MS are seeking helminth immunotherapy, clinical trial data do not currently support its use for people with MS.

Reliability of gait and dual-task measures in multiple sclerosis.

BACKGROUND: Single-task (ST) and dual-task (DT) assessments are commonly used to evaluate motor and cognitive impairment in people with multiple sclerosis (MS). Although variability can influence repeated DT testing measures, the reliability of several DT variables over time has not been adequately explored. For instance, a third testing session has never been included to observe whether DT has a learning effect. DT cognition rate reliability has not yet been examined and dual-task cost (DTC), a widely used calculation for DT interpretation, has not been proven reliable. RESEARCH QUESTION: To evaluate the reliability of ST and DT measures of gait and cognition over three test sessions. METHODS: This was a cross-sectional study involving 18 people with MS and 12 controls. Participants attended three test sessions, each one week apart. ST and DT (serial seven subtraction) gait variables, DTC, coefficient of variability (CV), and cognition rate were extracted and calculated using an instrumented walkway. Reliability was assessed using intraclass correlation coefficients (ICC) or Kendall's coefficient of concordance (KCC; nonparametric test) and minimum detectable change (MDC); between-session learning effect was assessed using repeated measures ANOVA. RESULTS: ICC/KCC values for ST and DT gait variables ranged from moderate to excellent (0.50-0.99). However, reliability for DT stride width and cognition rate was lower in controls. In general, DTC and CV variables had poor ICCs and high MDC values (49.19-1478.67 %), although some DTC variables had moderate or higher reliability in controls. Cognition rate was reliable in both MS (ICC 0.91) and controls (ICC 0.84). A learning effect between sessions was observed for DT velocity in both groups and for DTC cadence in people with MS. SIGNIFICANCE: ST and DT gait measures as well as DT cognition rate are reliable outcomes for repeated testing, while DTC and CV variables may not be suitable for long-term monitoring.

Under-treated depression negatively impacts lifestyle behaviors, participation and health-related quality of life among older people with multiple sclerosis.

PURPOSE: To what extent depression may negatively impact successful aging with multiple sclerosis (MS) is not known. We examined the impact of depression/depressive symptoms on lifestyle choices (diet, exercise, smoking and alcohol), participation and health-related quality of life (HRQoL) among older people living with MS (n = 742). METHODS: Based on self-reported depression diagnosis and scores on the Hospital Anxiety and Depression Scale, we divided the sample into four groups: 1. No depression diagnosis and low symptoms (n = 412), 2. Diagnosed with depression and low symptoms (n = 103), 3. Diagnosed with depression and high symptoms (n = 87), and 4. No depression diagnosis and high symptoms (n = 140). We used regression modelling to predict outcomes, controlling for age, MS disease duration, type of MS at initial diagnosis and disability. RESULTS: A high proportion (44.5%) reported either being diagnosed with depression, having high levels of symptoms or both. Only 12.1% reported that they were prescribed anti-depressants and 13.6% utilized psychosocial services. Compared to those with depression who had low symptoms, respondents who had high depressive symptoms (n = 227) were more likely to be non-exercisers (OR 1.85, 95%CI 1.02-3.34, p = 0.042), consume a poor diet (OR 2.12, 95%CI 1.27-3.52, p = 0.004), have the lowest levels of participation (OR 3.36, 95%CI 1.74-6.49, p = 0.0003) and report the poorest HRQoL (OR 1.95, 95%CI 1.17-3.26, p = 0.011). Men and people experiencing higher levels of disability and fatigue were at greater risk of having high symptoms and being undiagnosed. CONCLUSION: Undiagnosed and under-treated depression is common among older people living with MS and adversely impacts health choices.

A critical analysis of helminth immunotherapy in multiple sclerosis.

Helminthic worms are ancestral members of the intestinal ecosystem that have been largely eradicated from the general population in industrialized countries. Immunomodulatory mechanisms induced by some helminths mediate a "truce" between the mammalian host and the colonizing worm, thus allowing for long-term persistence in the absence of immune-mediated collateral tissue damage. This concept and the geographic discrepancy between global burdens of chronic inflammatory diseases and helminth infection have sparked interest in the potential of using helminthic worms as a therapeutic intervention to limit the progression of autoimmune diseases such as multiple sclerosis (MS). Here, we present and evaluate the evidence for this hypothesis in the pre-clinical animal model of MS, experimental autoimmune encephalitis, in helminth-infected MS patients and in clinical trials of administered helminth immunotherapy (HIT).

A systematic review of reviews: Recruitment and retention of rural family physicians.

INTRODUCTION: The recruitment and retention of family physicians in rural and remote communities has been the topic of many reviews; however, a lack of consensus among them with regard to which factors are most influential makes it difficult for setting priorities. We performed a systematic review of reviews which helped to establish an overall conclusion and provided a set of fundamental influential factors, regardless of the consistency or generalisability of the findings across reviews. This review also identified the knowledge gaps and areas of priority for future research. METHODS: A literature search was conducted to find the review articles discussing the factors of recruitment or retention of rural family physicians. Results were screened by two independent reviewers. The number of times that each factor was mentioned in the literature was counted and ordered in terms of frequency. RESULTS: The literature search identified 84 systematic reviews. Fourteen met the inclusion criteria, from which 158 specific factors were identified and summarised into 11 categories: personal, health, family, training, practice, work, professional, pay, community, regional and system/legislation. The three categories referenced most often were training, personal and practice. The specific individual factors mentioned most often in the literature were 'medical school characteristics', 'longitudinal rural training' and 'raised in a small town'. CONCLUSION: The three most often cited categories resemble three distinct phases of a family physician's life: pre-medical school, medical school and post-medical school. To increase the number of physicians who choose to work in rural practice, strategies must encompass and promote continuity across all three of these phases. The results of this systematic review will allow for the identification of areas of priority that require further attention to develop appropriate strategies to improve the number of family physicians working in rural and remote locations.

Résumé Introduction: Le recrutement et la rétention des médecins de famille dans les communautés rurales et éloignées ont fait l'objet de nombreuses revues; il est toutefois difficile d'établir les priorités en la matière en raison de l'absence de consensus quant aux facteurs ayant la plus grande influence. Nous avons mené une revue systématique des revues qui nous a aidés à tirer une conclusion d'ensemble et à réunir une série de facteurs fondamentaux d'influence, sans égard à l'uniformité des observations des revues ni à la possibilité de les généraliser. Les résultats de cette revue systématique nous permettront de déterminer quels sont les domaines prioritaires auxquels nous devons nous attarder dans le but d'élaborer les stratégies appropriées qui multiplieront le nombre de médecins de famille en région rurale ou éloignée. Cette revue a aussi fait ressortir les lacunes et les domaines prioritaires en recherche. Méthodologie: La littérature publiée a été recherchée pour trouver les articles de synthèse traitant des facteurs de recrutement ou de rétention des médecins de famille en région rurale. Les résultats ont été dépouillés par deux réviseurs indépendants. Le nombre de fois où chaque facteur était mentionné dans les publications était compté et classé en fonction de la fréquence. Résultats: La recherche de la littérature a relevé 84 revues systématiques. Quatorze répondaient aux critères d'inclusion; de celles-là, 158 facteurs ont été définis et résumés en 11 catégories : personnel, santé, famille, formation, pratique, travail, professionnel, rémunération, communauté, régional et système/législation. Les trois catégories qui sont revenues le plus souvent étaient formation, personnel et pratique. Les facteurs individuels mentionnés le plus souvent dans la littérature étaient" caractéristiques de l'école de médecine", "formation rurale longitudinale" et "grandi dans un village". Conclusion: Les trois catégories citées le plus souvent ressemblent à trois phases distinctes de la vie d'un médecin de famille : avant l'école de médecine, école de médecine et après l'école de médecine. Pour augmenter le nombre de médecins qui choisissent la pratique rurale, les stratégies doivent inclure et favoriser la continuité entre ces trois phases. Mots-clés: médecin de famille, recrutement, rétention, rural, revue systématique de revues.

Exploring the utility of the Nursing Role Effectiveness Model in evaluating nursing contributions in primary health care: A scoping review.

AIMS: To inform a discussion for the applicability of using the Nursing Role Effectiveness Model (NREM) in the primary health care setting through a synthesis of the literature that has used the model in all health care sectors. DESIGN: Scoping Review. METHODS: Articles were considered for inclusion if they discussed any aspect of the NREM in health care research that presented information related to any nursing regulatory designation, such as nurse practitioner (NP), registered nurse (RN), licensed/registered practical nurse (LPN/RPN) and considered both quantitative and qualitative study designs, including expert opinions and reports. RESULTS: A total of 22 articles that cited and/or used the NREM were identified in this review. Only two studies were focused in the primary health care setting. There is precedence for the use of the NREM to guide research in primary health care. The NREM should be modified to incorporate the unique characteristics of the primary health care setting.

Identifying Indicators of National Council Licensure Examination for Registered Nurses (NCLEX-RN) Success in Nursing Graduates in Newfoundland & Labrador.

In Canada in 2015, the pass rates on the National Council Licensure Examination (NCLEX-RN) were considerably lower than pass rates on the Canadian Registered Nurse Examination (CRNE) causing nurse educators to express concern regarding the NCLEX-RN. The purpose of this study was to examine the relationship between candidate variables (e. g. academic performance, demographics) on their NCLEX-RN outcome (pass/fail). A cross-sectional data linkage design was employed using multiple sources of data on nursing graduates who wrote the NCLEX-RN in 2015, 2016 and 2017 (n = 259). Results showed that fewer questions answered on the NCLEX-RN and higher grades in various nursing courses (e. g. Introduction to Nursing, Statistics) predicted higher odds of passing the NCLEX-RN. To improve pass rates, nurse educators must integrate diverse methods of testing into existing curricula that mimic the NCLEX-RN exam, specifically computer adaptive exams. Further research is needed to determine other possible challenges for countries considering adopting the NCLEX-RN.

Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke.

BACKGROUND: Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. METHODS: Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNFresting) and after a graded exercise test (BDNFresponse) and insulin-like growth factor-1 at the same timepoints (IGF-1rest, IGF-1response). RESULTS: At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games -8.5%). Greater IGF-1response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNFresting or BDNFresponse; nor was BDNF predictive of the outcome. CONCLUSIONS: Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke.

OBJECTIVES: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels. METHODS: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor. RESULTS: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1. DISCUSSION: Biomarkers have the potential to characterize an individual's potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Excessive sedentary time during in-patient stroke rehabilitation.

Background and Purpose Previous research suggests that patients receiving inpatient stroke rehabilitation are sedentary although there is little data to confirm this supposition within the Canadian healthcare system. The purpose of this cross-sectional study was to observe two weeks of inpatient rehabilitation in a tertiary stroke center to determine patients' activity levels and sedentary time. Methods Heart rate (HR) and accelerometer data were measured using an Actiheart monitor for seven consecutive days, 24 h/day, on the second week and the last week of admission. Participants or their proxies completed a daily logbook. Metabolic equivalent (MET) values were calculated and time with MET < 1.5 was considered sedentary. The relationship between patient factors (disability, mood, and social support) and activity levels and sedentary time were analyzed. Results Participants (n = 19; 12 males) spent 10 h sleeping and 4 h resting each day, with 86.9% of their waking hours sedentary. They received on average 8.5 task-specific therapy sessions; substantially lower than the 15 h/week recommended in best practice guidelines. During therapy, 61.6% of physical therapy and 76.8% of occupational therapy was spent sedentary. Participants increased their HR about 15 beats from baseline during physical therapy and 8 beats during occupational therapy. There was no relationship between sedentary time or activity levels and patient factors. Discussion Despite calls for highly intensive stroke rehabilitation, there was excessive sedentary time and therapy sessions were less frequent and of lower intensity than recommended levels. Conclusions In this sample of people attending inpatient stroke rehabilitation, institutional structure of rehabilitation rather than patient-related factors contributed to sedentary time.

Bipedal hopping timed to a metronome to detect impairments in anticipatory motor control in people with mild multiple sclerosis.

BACKGROUND: People with mild multiple sclerosis (MS) often report subtle deficits in balance and cognition but display no measurable impairment on clinical assessments. We examined whether hopping to a metronome beat had the potential to detect anticipatory motor control deficits among people with mild MS (Expanded Disability Status Scale ≤ 3.5). METHODS: Participants with MS (n = 13), matched controls (n = 9), and elderly subjects (n = 13) completed tests of cognition (Montreal Cognitive Assessment (MoCA)) and motor performance (Timed 25 Foot Walk Test (T25FWT)). Participants performed two bipedal hopping tasks: at 40 beats/min (bpm) and 60-bpm in random order. Hop characteristics (length, symmetry, variability) and delay from the metronome beat were extracted from an instrumented walkway and compared between groups. RESULTS: The MS group became more delayed from the metronome beat over time whereas elderly subjects tended to hop closer to the beat (F = 4.52, p = 0.02). Delay of the first hop during 60-bpm predicted cognition in people with MS (R = 0.55, ß = 4.64 (SD 4.63), F = 4.85, p = 0.05) but not among control (R = 0.07, p = 0.86) or elderly subjects (R = 0.17, p = 0.57). In terms of hopping characteristics, at 60-bpm, people with MS and matched controls were significantly different from the elderly group. However, at 40-bpm, the MS group was no longer significantly different from the elderly group, even though matched controls and elderly still differed significantly. CONCLUSIONS: This new timed hopping test may be able to detect both physical ability, and feed-forward anticipatory control impairments in people with mild MS. Hopping at a frequency of 40-bpm seemed more challenging. Several aspects of anticipatory motor control can be measured: including reaction time to the first metronome cue and the ability to adapt and anticipate the beat over time.

Therapists' cues influence lower limb muscle activation and kinematics during gait training in subacute stroke.

PURPOSE: Symmetrical gait is a key goal of rehabilitation post-stroke. Therapists employ techniques such as verbal instruction and haptic cues to increase activation of paretic muscles. We examined whether verbal or tactile cueing altered spatiotemporal gait parameters, kinematics and electromyography (EMG) of lower limb muscles on the more-affected side within a training session. MATERIALS AND METHODS: Patients (n = 10) were recruited from rehabilitation services (<9 months post-stroke). Tactile (to the hip muscles) or verbal cues were provided on two testing days, 7-10 days apart (randomized order). Gait and angular kinematics were recorded using a Vicon motion capture system and muscle activation using EMG; at baseline (PRE), during the cue, directly afterwards without a cue (POST) and 20 min later without a cue (RETEST). RESULTS: Both verbal and tactile cueing significantly increased muscle activity in paretic muscles but with no immediate effect on step length asymmetry. Tactile cues, more than verbal, temporarily altered gait speed, cadence and time in double support. Verbal cues caused more robust increases in muscle activation of vastus lateralis at weight acceptance and medial gastrocnemius activity from toe off to midswing. CONCLUSIONS: Within a treatment session, tactile cues more effectively altered cadence and double support time while verbal cues more consistently increased vastus lateralis and medial gastrocnemius activity. The effectiveness of these methods in fostering motor relearning in the longer term is an important area for future research. Implications for Rehabilitation Therapist cueing alters muscle activity on hemiparetic side with no effects on symmetry. Tactile cues, more so than verbal cues, increase cadence and reduce time in double support. Verbal cues are more effective at increasing vastus lateralis and plantarflexor muscle activity.