Screening for Anxiety and Depression Symptoms Using Concussion Symptom Scales Among Varsity Athletes.

OBJECTIVE: This study examined associations between Sport Concussion Assessment Tool-5 (SCAT-5) symptom reporting and gold-standard measures of anxiety and depression, and explored the utility SCAT-5 symptom subscales to identify anxiety and depression symptomology. DESIGN: Prospective cross-sectional study. SETTING: York University in Toronto, Canada. PARTICIPANTS: Preseason data were collected for varsity athletes (N = 296) aged between 17 and 25 years ( M = 20.01 years, SD = 1.69 years; 52% male). MAIN OUTCOME MEASURES: The SCAT-5 symptom evaluation scale was used to assess baseline symptoms. The Generalized Anxiety Disorder Index-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess symptoms of anxiety and depression, respectively. RESULTS: Endorsement of SCAT-5 symptoms of feeling anxious, sadness, irritability, and feeling more emotional had the strongest correlations with the GAD-7 ( r' s > 0.400; P' s < 0.001). Sadness, trouble falling asleep, concentration problems, feeling slowed down, anxious, irritability, mental fog, fatigue, and memory problems had the highest correlations with the PHQ-9 ( r' s >0 .400; P' s < 0.001). The Emotional subscale from the SCAT-5 predicted mild to severe anxiety on the GAD-7 ( P < 0.001). The Sleep, Cognitive, and Emotional subscales predicted mild to severe depression on the PHQ-9 ( P' s < 0.05). CONCLUSIONS: These findings provide better delineation of symptoms endorsed on the SCAT-5 symptoms that aid in identification of athletes with symptoms of anxiety or depression who may be at risk for developing a clinical disorder or experiencing persistent symptoms after a concussion.

Adjusting to life after pediatric stroke: A qualitative study.

AIM: To examine adjustment after stroke in adolescence from the perspective of affected young people. METHOD: Fourteen participants (10 female) aged 13 to 25 years with a history of ischemic or hemorrhagic stroke in adolescence participated in one-on-one semi-structured interviews at the Hospital for Sick Children, Toronto, Canada. Interviews were audio-recorded and transcribed verbatim. Two independent coders conducted a reflexive thematic analysis. RESULTS: Five themes were identified as representative of adjustment after stroke: (1) 'Processing the story'; (2) 'Loss and challenges'; (3) 'I've changed'; (4) 'Keys to recovery'; and (5) 'Adjustment and acceptance'. INTERPRETATION: This qualitative study provides medical professionals with a personal, patient-driven lens through which to better understand the challenges of adjusting to life after pediatric stroke. Findings highlight the need to provide mental health support to patients to assist them in processing their stroke and adapting to long-lasting sequelae. WHAT THIS PAPER ADDS: Processing the onset event is a key component of adjustment to stroke. Feelings of anxiety, sadness, frustration, and self-consciousness impede adjustment to stroke. Young people may feel overwhelmed academically owing to neurocognitive deficits. Sequelae may rid young people of hobbies and passions, and alter plans for the future. To adjust to stroke, survivors draw on resilience, patience, determination, and social support.

Integrating Contact Tracers Into Point-of-Care Testing Workflow to Accelerate the Tracing of People With Exposure to COVID-19, August-December 2020, New York City.

OBJECTIVES: We assessed the timeliness of contact tracing following rapid-positive COVID-19 test result at point-of-care testing (POCT) sites in New York City (NYC). DESIGN: Interviewed case-patients to elicit exposed contacts and conducted COVID-19 exposure notifications. SETTINGS: Twenty-two COVID-19 POCT sites in NYC, the 2 NYC international airports, and 1 ferry terminal. PARTICIPANTS: Case-patients with rapid-positive COVID-19 test results and their named contacts. MAIN OUTCOME MEASURES: We quantified the proportions of interviewed individuals with COVID-19 and notified contacts and assessed the timeliness between the dates of the rapid-positive COVID-19 test results and the interviews or notifications. RESULTS: In total, 11 683 individuals with rapid-positive COVID-19 test results were referred for contact tracing on the day of their diagnosis; 8878 (76) of whom were interviewed within 1 day of diagnosis, of whom 5499 (62%) named 11 486 contacts. A median of 1.24 contacts were identified from each interview. The odds of eliciting contacts were significantly higher among individuals reporting COVID-19 symptoms than among persons with no symptoms (51% vs 36%; adjusted odds ratio [aOR] = 1.37; 95% confidence interval [CI], 1.11-1.70) or living with 1 or more persons than living alone (89% vs 38%; aOR = 12.11; 95% CI, 10.73-13.68). Among the 8878 interviewed case-patients, 8317 (94%) were interviewed within 1 day of their rapid-positive COVID-19 test results and 91% of contact notifications were completed within 1 day of contact identification. The median interval from test result to interview date and from case investigation interview to contact notification were both 0 days (IQR = 0). CONCLUSIONS: The integration of contact tracers into COVID-19 POCT workflow achieved timely case investigation and contact notification. Accelerated contact tracing can be used to curb COVID-19 transmission during local outbreaks.

Evidence of altered interhemispheric communication after pediatric concussion.

OBJECTIVES: To investigate neurophysiological alterations within the typical symptomatic period after concussion (1-month) and throughout recovery (6-months) in adolescents; and (2) to examine relationships between neurophysiological and upper limb kinematic outcomes.METHODS: 18 adolescents with concussion were compared to 17 healthy controls. Transcranial magnetic stimulation (TMS) was used to assess neurophysiological differences between groups including: short- and long-interval intracortical inhibition, intracortical facilitation, short- and long-latency afferent inhibition, afferent facilitation, and transcallosal inhibition (TCI). Behavioral measures of upper limb kinematics were assessed with a robotic device.RESULTS: Mixed model analysis of neurophysiological data identified two key findings. First, participants with concussion demonstrated delayed onset of interhemispheric inhibition, as indexed by TCI, compared to healthy controls. Second, our exploratory analysis indicated that the magnitude of TCI onset delay in adolescents with concussion was related to upper limb kinematics.CONCLUSIONS: Our findings indicate that concussion in adolescence alters interhemispheric communication. We note relationships between neurophysiological and kinematic data, suggesting an affinity for individuals with less concussion-related physiological change to improve their motor behavior over time. These data serve as an important step in future development of assessments (neurobiological and clinical) and interventions for concussion.

Open Globe Injuries Presenting With Normal or High Intraocular Pressure.

OBJECTIVES: To determine the frequency, clinical characteristics, and visual outcomes of patients who present with high or normal intraocular pressure (IOP) and open globe injuries. DESIGN: Retrospective chart review. SETTING: University of Maryland Medical Center, a level 1 trauma center. PATIENT OR STUDY POPULATION: All cases of open globe injury presenting to The University of Maryland Medical Center from July 2005 to January 2014. OBSERVATION: Demographics, initial physical examination, computed tomography findings, IOP of the affected and unaffected eyes, and follow-up evaluations. MAIN OUTCOME MEASURES: (1) IOP 10 mm Hg or greater and (2) visual acuity. RESULTS: Of 132 eyes presenting with open globe injury, IOP was recorded in 38 (28%). Mean IOP for the affected and unaffected eyes was 14±10.3 mm Hg and 16.6±4.1 mm Hg, respectively. Twenty-three (59.4%) eyes had IOP greater than 10 mm Hg. Six eyes (16.2%) had IOP greater than 21 mm Hg. Using bivariate analysis, IOP greater than 10 mm Hg was associated with posterior open globe injury (P=0.01), posterior hemorrhage (P=0.04), and intraconal retrobulbar hemorrhage (P=0.05). Adjusting for age, sex, and race, IOP greater than 10 mm Hg was associated with the presence of posterior open globe injury on clinical examination (P=0.04). Higher presenting IOP was found to predict light perception or worse vision (P=0.01). Multivariate analysis showed that poor presenting vision was the best predictor of poor final vision (P<0.01). CONCLUSIONS: High IOP does not exclude open globe injury. It is a frequent finding in patients with open globe injuries and may be associated with posterior injury and poor visual prognosis.

Predictors of neurocognitive outcome in pediatric ischemic and hemorrhagic stroke.

This clinical study examined the impact of eight predictors (age at stroke, stroke type, lesion size, lesion location, time since stroke, neurologic severity, seizures post-stroke, and socioeconomic status) on neurocognitive functioning following pediatric stroke. Youth with a history of pediatric ischemic or hemorrhagic stroke (n = 92, ages six to 25) underwent neuropsychological testing and caregivers completed parent-report questionnaires. Hospital records were accessed for medical history. Spline regressions, likelihood ratios, one-way analysis of variance, Welch's t-tests, and simple linear regressions examined associations between predictors and neuropsychological outcome measures. Large lesions and lower socioeconomic status were associated with worse neurocognitive outcomes across most neurocognitive domains. Ischemic stroke was associated with worse outcome in attention and executive functioning compared to hemorrhagic stroke. Participants with seizures had more severe executive functioning impairments than participants without seizures. Youth with cortical-subcortical lesions scored lower on a few measures than youth with cortical or subcortical lesions. Neurologic severity predicted scores on few measures. No differences were found based on time since stroke, lesion laterality, or supra- versus infratentorial lesion. In conclusion, lesion size and socioeconomic status predict neurocognitive outcome following pediatric stroke. An improved understanding of predictors is valuable to clinicians who have responsibilities related to neuropsychological assessment and treatments for this population. Findings should inform clinical practice through enhanced appraisals of prognosis and the use of a biopsychosocial approach when conceptualizing neurocognitive outcome and setting up support services aimed at fostering optimal development for youth with stroke.

Efficacy and safety of Elaeis guineensis and Ficus deltoidea leaf extracts in adults with pre-diabetes.

BACKGROUND: Individuals with pre-diabetes (fasting glucose 100-125 mg/dl) are at increased risk of developing diabetes; 50% of U.S. adults aged ≥65 y had pre-diabetes in 2005-08. Extracts of the leaves of E. guineensis (a tropical plant producing edible oil), and F. deltoidea (a traditional tea) contain phenolic compounds that have hypoglycemic effects in vitro and in vivo. Therefore, a study of the efficacy and safety of these leaf extracts was undertaken. METHODS: Otherwise healthy adults with pre-diabetes (15m/15f; aged 21 to 65 y; BMI ≥25 and < 40 kg/m²) were assigned to one of 3 groups for 8 weeks: E. guineensis leaf extract 500 mg or 1000 mg or F. deltoidea leaf extract 1000 mg. Assessments at baseline and throughout the study included: fasting plasma glucose, insulin, OGTT, and HOMA-IR; body weight and waist circumference; vital signs, comprehensive metabolic and lipid panels. Statistical analyses included paired Student's t-test and ANCOVA or non-parametric tests when indicated. RESULTS: E. guineensis intervention for 8 weeks decreased fasting plasma glucose and insulin levels, glucose and insulin areas under the curve, and insulin resistance, and increased insulin sensitivity. The 500 mg dose of E. guineensis had a more consistent effect on reducing glycemia than the 1000 mg dose and the insulin findings at the two dose levels were somewhat inconsistent. Differences in the distribution of baseline insulin levels in the low and high dose groups may explain some of these observed differences in responses. F. deltoidea leaf extract had no effect on glycemia variables but both total and LDL cholesterol concentrations were significantly decreased in this group. There were no significant differences in change of weight; however waist circumference was significantly lower in the E. guineensis groups after intervention. At baseline and after 8 weeks of intervention, vital signs and safety lab tests were within normal limits and not significantly different between groups or due to intervention. CONCLUSIONS: These results suggest that the leaf extracts of E. guineensis and F. deltoidea may have positive effects on glucose and lipid levels and are safe for use in humans. Further study is required to determine the maximum effective dosages and the mechanisms of action.

Adherence to and Motivations for Complying With Public Health Measures Among Adolescents During the Coronavirus Disease (COVID-19) Pandemic in Canada.

Background: Public health measures (e.g., minimizing social interactions, social distancing, and mask wearing) have been implemented in Canada to reduce the transmission of COVID-19. Given that adolescents may be a high-risk demographic for spreading COVID-19, this study investigated adherence to and motivations for complying with public health measures among Canadian youth at two points of the COVID-19 pandemic. Methods: Adolescents (N = 1,484, 53% girls, Mage = 15.73 [SD = 1.41]) completed an online survey in either Summer 2020 (Cohort 1 [C1]; n = 809, 56% girls) or Winter 2020/2021 (Cohort 2 [C2]; n = 675, 50% girls). We investigated differences in adherence across cohorts using independent sample t-tests and predictors of adherence using a path analysis. Results: Youth engaged in similar levels of social interaction in C1 and C2. Relative to adolescents in C1, adolescents in C2 reported more mask wearing, but less social distancing. Social responsibility was associated with adherence to almost all public health measures across both cohorts, with one exception: it did not predict minimizing social interactions in C2. Not wanting to get sick predicted minimizing social interactions and mask wearing. Concern with population health predicted adherence to all public health measures in C1 and all but mask wearing in C2. Maintaining social ties was negatively associated with minimizing social interactions in both cohorts, and with social distancing in C1. Conclusions: Youth engaged in more mask wearing but less social distancing as the pandemic progressed. Social responsibility and not wanting to get sick were consistent predictors of adherence to most public health measures throughout the pandemic. Youth shifted away from adhering to mask wearing measures due to concern with population health over the course of the pandemic. These results can inform targeted campaigns to bolster compliance with public health measures among adolescents.

Consensus-Based Evaluation of Outcome Measures in Pediatric Stroke Care: A Toolkit.

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, validity, feasibility, and predictive utility. A total of 48 outcome measures were included and were rated by experts based on the available evidence within the literature supporting the strengths of their psychometric properties and practical use. Only three measures were found to be validated for use in pediatric stroke: the Pediatric Stroke Outcome Measure, the Pediatric Stroke Recurrence and Recovery Questionnaire, and the Pediatric Stroke Quality of Life Measure. However, multiple additional measures were deemed to have good psychometric properties and acceptable utility for assessing pediatric stroke outcomes. Strengths and weaknesses of commonly used measures including feasibility are highlighted to guide evidence-based and practicable outcome measure selection. Improving the coherence of outcome assessment will facilitate comparison of studies and enhance research and clinical care in children with stroke. Further work is urgently needed to close the gap and validate measures across all clinically significant domains in the pediatric stroke population.

Roadmap for the Assessment and Management of Outcomes in Pediatric Stroke.

Neurological morbidity is common after pediatric stroke, with moderate to severe deficits that can significantly impact education and social function. Care and recovery occur in phases distinguished by the time interval after stroke onset. These phases include the hyperacute and acute periods in which the focus is on cerebral reperfusion and prevention of neurological deterioration, followed by the subacute and chronic phases in which the focus is on secondary stroke prevention and mitigation of disability through rehabilitation, adaptation, and reintegration into the community. In this article, a multidisciplinary group of pediatric stroke experts review the stages of recovery after pediatric stroke with an emphasis on critical assessment time points. Our goal is to encourage increased standardization of outcome assessment to facilitate future clinical trials comparing various treatment and intervention options and advance optimized care for children with stroke.

Traumatic brain injury in precariously housed persons: Incidence and risks.

BACKGROUND: Homeless and precarious housed persons are particularly prone to traumatic brain injuries (TBIs), but existent incidence rates are hampered by poor case acquisition. We rigorously documented TBIs in precariously housed persons transitioning in and out of homelessness. METHODS: Between December 2016 and May 2018, 326 precariously housed participants enrolled in a longitudinal study in Vancouver, Canada were assessed monthly for TBI occurrences after education on sequelae. Over one participant-year, 2433 TBI screenings were acquired for 326 person-years and variables associated with odds of incident TBI were evaluated. FINDINGS: One hundred participants acquired 175 TBIs, yielding an observed incidence proportion of 30·7% and event proportion of 53·7%. Of the injured, 61% reported one TBI and 39% reported multiple injuries. Acute intoxication was present for more than half of the TBI events assessed. Additionally, 9·7% of TBI events occurred in the context of a drug overdose. Common injury mechanisms were falls (45·1%), assaults (25·1%), and hitting one's head on an object (13·1%). In this community-based but non-randomly recruited sample, exploratory analyses identified factors associated with odds of an incident TBI over one year of follow-up, including: schizophrenia disorders (odds ratio (OR) = 0·43, 95% confidence interval (CI) 0·19, 0·94), role functioning (OR = 0·69, 95% CI 0·52, 0·91), opioid dependence (OR = 2·17, 95% CI 1·27, 3·72) and those reporting past TBIs (OR = 1·99, 95% CI 1·13, 3·52). INTERPRETATION: Given the ubiquity of TBIs revealed in this precariously housed sample, we identify an underappreciated and urgent healthcare priority. Several factors modified the odds of incident TBI, which can facilitate investigations into targeted prevention efforts. FUNDING: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, William and Ada Isabelle Steel Research Fund, Simon Fraser University Vice-President Research Undergraduate Student Research Award and Simon Fraser University Psychology Department Research Grant.

Acute Exercise Modulates the Excitability of Specific Interneurons in Human Motor Cortex.

Acute exercise can modulate the excitability of the non-exercised upper-limb representation in the primary motor cortex (M1). Accumulating evidence demonstrates acute exercise affects measures of M1 intracortical excitability, with some studies also showing altered corticospinal excitability. However, the influence of distinct M1 interneuron populations on the modulation of intracortical and corticospinal excitability following acute exercise is currently unknown. We assessed the impact of an acute bout of leg cycling exercise on unique M1 interneuron excitability of a non-exercised intrinsic hand muscle using transcranial magnetic stimulation (TMS) in young adults. Specifically, posterior-to-anterior (PA) and anterior-to-posterior (AP) TMS current directions were used to measure the excitability of distinct populations of interneurons before and after an acute bout of exercise or rest. Motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) were measured in the PA and AP current directions in M1 at two time points separated by 25 min of rest, as well as immediately and 30 min after a 25-minute bout of moderate-intensity cycling exercise. Thirty minutes after exercise, MEP amplitudes were significantly larger than other timepoints when measured with AP current, whereas MEP amplitudes derived from PA current did not show this effect. Similarly, SICI was significantly decreased immediately following acute exercise measured with AP but not PA current. Our findings suggest that the excitability of unique M1 interneurons are differentially modulated by acute exercise. These results indicate that M1 interneurons preferentially activated by AP current may play an important role in the exercise-induced modulation of intracortical and corticospinal excitability.

A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms.

BACKGROUND: This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. METHODS: Sixty-one adults were enrolled (age 36.5 +/- 12.6 years; height 165.1 +/- 9.2 cm; weight 75.4 +/- 17.3 kg) and randomized to either Digestive Advantage Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. RESULTS: Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. CONCLUSION: In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00881322.

A pilot trial comparing the availability of vitamins C, B6, and B12 from a vitamin-fortified water and food source in humans.

PRIMARY OBJECTIVE: In a cross-over randomized pilot study, the relative absorption of vitamins C, B(6) and B(12) were tested using a commercial vitamin-water (VW) and a standardized mixed meal (MM). METHODS AND PROCEDURES: Twelve adults (22.9+/-3.7 years), received the VW and the MM, randomly ordered, with a minimum 7-day washout period between. Blood was drawn pre-ingestion and over a post-ingestion period of 300+ min. Test meal quantities were formulated to contain equal amounts of vitamins B(6), B(12), and C as per the water label. Analysis revealed that a scaling factor had to be used to balance the actual content differences between test products. MAIN OUTCOMES AND RESULTS: Using the adjusted numbers for actual water vitamin concentration, there were no differences in the maximum concentration and the 5-h area under the curve for vitamins B(6), B(12) or C between the VW and the MM. CONCLUSIONS: VW was found to provide similar in vivo nutrition as the test MM at a caloric saving.

Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial.

BACKGROUND: Recent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora) on anxiety, stress and sleep in healthy premenopausal women. METHODS: This randomized, parallel, placebo controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules) or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL. RESULTS: The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo. CONCLUSION: This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.

Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.

BACKGROUND: The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. OBJECTIVES: The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. METHODS: Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. RESULTS: Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. CONCLUSION: Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.

A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males.

PURPOSE: The purpose of this study was to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of an oral inositol-stabilized arginine silicate dietary supplement. SUBJECTS AND METHODS: Ten healthy males, 26.7±5.4 years, took three 500 mg arginine silicate capsules (active product) for 14 days. The subjects attended test visits on Days 1 and 14. Fasting blood and saliva collections were performed predose and at 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, and 6 hours postdose for plasma arginine, serum silicon, and salivary nitric oxide (NO) + nitrite. RESULTS: Day 1 PK parameters (adjusted for body weight) for arginine were peak serum concentration (C Max) 30.06±7.80 µg/mL, time it takes to reach peak serum concentration (t Max) 1.13±0.52 hours, and time required to reach half its original concentration (t 1/2) 15.93±9.55 hours and for silicon were C Max 2.99±0.63 µg/mL, t Max 2.44±2.05 hours, and t 1/2 34.56±16.56 hours. After Day 1 dose, arginine levels increased at 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, and 5 hours (P<0.01) and silicon levels increased at 1 hour and 1.5 hours (P<0.05). After Day 14 dose, arginine levels increased at 0.5 hours, 1 hour, and 1.5 hours (P<0.05) and silicon levels increased at 1 hour, 1.5 hours, 2 hours, and 3 hours (P<0.01). After 14 days of use, baseline arginine trended toward being higher than baseline Day 1 (P=0.0645), and 4-hour postdose plasma arginine was significantly higher (P=0.0488) at Day 14 than Day 1. Although not a significant difference, NO, as measured as salivary nitrate, increased in four subjects and stayed the same in six subjects at 0.5 hours after the first dose (P=0.125). After 14 days of use, baseline NO levels increased in six subjects and stayed the same in four subjects; this shift was significant (P=0.031). CONCLUSION: The arginine silicate dietary supplement increases blood levels of arginine after a single dose within 30 minutes and blood levels of silicon for up to 1.5 hours. Blood levels of arginine, silicon, and NO (salivary nitrite) were elevated consistently after 14 days of use. The observed increase in baseline salivary nitrite is supporting information that there was some improvement in NO production. Further study on the effect of this supplement on NO production and the resulting physiological effect is warranted. Within the specific protocol of this study, the product was found to be safe.

A Prospective Randomized Double-Blind Study Evaluating UP165 and S-Adenosyl-l-Methionine on Depression, Anxiety and Psychological Well-Being.

The primary objective of this pilot clinical trial was to evaluate the effects of UP165 (derived from Zea mays L., commonly known as corn) over time. The secondary objective was the comparison for outcomes versusS-adenosyl-methionine (SAM-e). Subjects with mild depression or anxiety were given the Beck Depression Inventory second edition (BDI-II), the Beck Anxiety Inventory (BAI), and the Schwartz Outcome Scale (SOS-10). Forty-two subjects (21-65 years old) were randomized to eight-weeks of supplementation with UP165 or SAM-e with questionnaires being administered at randomization, week four and eight. Those receiving UP165 achieved significant reduction from baseline at weeks four and eight, respectively for the BDI-II, as well as a trend for reduction in BAI at week four and significance at week eight. There was a trend for improvement on the SOS at week four and significance at week eight. SAM-e demonstrated a trend for improvement on the BDI-II by week eight over the UP165 with no differences between the two for the BAI or the SOS. Overall, this study indicates that there may be benefit to UP165 for mood enhancement in those with mild depression or anxiety. Randomized placebo comparator trials appear warranted.

Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer's disease mouse model.

INTRODUCTION: Recent studies have shown that several strains of transgenic Alzheimer's disease (AD) mice overexpressing the amyloid precursor protein (APP) have cortical hyperexcitability, and their results have suggested that this aberrant network activity may be a mechanism by which amyloid-ß (Aß) causes more widespread neuronal dysfunction. Specific anticonvulsant therapy reverses memory impairments in various transgenic mouse strains, but it is not known whether reduction of epileptiform activity might serve as a surrogate marker of drug efficacy for memory improvement in AD mouse models. METHODS: Transgenic AD mice (APP/PS1 and 3xTg-AD) were chronically implanted with dural electroencephalography electrodes, and epileptiform activity was correlated with spatial memory function and transgene-specific pathology. The antiepileptic drugs ethosuximide and brivaracetam were tested for their ability to suppress epileptiform activity and to reverse memory impairments and synapse loss in APP/PS1 mice. RESULTS: We report that in two transgenic mouse models of AD (APP/PS1 and 3xTg-AD), the presence of spike-wave discharges (SWDs) correlated with impairments in spatial memory. Both ethosuximide and brivaracetam reduce mouse SWDs, but only brivaracetam reverses memory impairments in APP/PS1 mice. CONCLUSIONS: Our data confirm an intriguing therapeutic role of anticonvulsant drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice, despite reduction of SWDs. Our data indicate that SWDs are not a reliable surrogate marker of appropriate target engagement for reversal of memory dysfunction in APP/PS1 mice.

Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study.

BACKGROUND: Methylsulfonylmethane (MSM) has been reported to provide anti-inflammatory and antioxidant effects in both animal and man. Strenuous resistance exercise has the potential to induce both inflammation and oxidative stress. Using a pilot (proof of concept) study design, we determined the influence of MSM on markers of exercise recovery and performance in healthy men. METHODS: Eight, healthy men (27.1 ± 6.9 yrs old) who were considered to be moderately exercise-trained (exercising <150 minutes per week) were randomly assigned to ingest MSM at either 1.5 grams per day or 3.0 grams per day for 30 days (28 days before and 2 days following exercise). Before and after the 28 day intervention period, subjects performed 18 sets of knee extension exercise in an attempt to induce muscle damage (and to be used partly as a measure of exercise performance). Sets 1-15 were performed at a predetermined weight for 10 repetitions each, while sets 16-18 were performed to muscular failure. Muscle soreness (using a 5-point Likert scale), fatigue (using the fatigue-inertia subset of the Profile of Mood States), blood antioxidant status (glutathione and Trolox Equivalent Antioxidant Capacity [TEAC]), and blood homocysteine were measured before and after exercise, pre and post intervention. Exercise performance (total work performed during sets 16-18 of knee extension testing) was also measured pre and post intervention. RESULTS: Muscle soreness increased following exercise and a trend was noted for a reduction in muscle soreness with 3.0 grams versus 1.5 grams of MSM (p = 0.080), with a 1.0 point difference between dosages. Fatigue was slightly reduced with MSM (p = 0.073 with 3.0 grams; p = 0.087 for both dosages combined). TEAC increased significantly following exercise with 3.0 grams of MSM (p = 0.035), while homocysteine decreased following exercise for both dosages combined (p = 0.007). No significant effects were noted for glutathione or total work performed during knee extension testing (p > 0.05). CONCLUSION: MSM, especially when provided at 3.0 grams per day, may favorably influence selected markers of exercise recovery. More work is needed to extend these findings, in particular using a larger sample of subjects and the inclusion of additional markers of exercise recovery and performance.