Sensorimotor functioning changes in response to global exercise versus handwriting upper limb exercise training in Parkinson's disease, results from a phase II randomised controlled trial.

INTRODUCTION: People with Parkinson's disease (PwPD) present motor alterations which can impact daily life tasks that require speed and/or accuracy of movement. OBJECTIVE: A sub analysis of NCT01439022, aiming to estimate the extent to which two different exercise training protocols (global and handwriting upper limb exercise training) impact reaction time, travel speed, and accuracy in PwPD. METHODS: Seventy PwPD, right-side dominant were randomised 1:1 into two six-month training protocol groups; 35 PwPD performed global exercise training and 35 performed specific training (handwriting upper limb exercise movements). Assessments of speed-accuracy and trade-off were carried out at baseline, after 3 and 6 months of training, and at a 12-month follow-up. The current study used data from a previous publication of a randomised controlled trial that included a 6-month self-managed community exercise programme for PwPD. For the present study we included only the participants who completed the Fitts' task during the baseline assessment. RESULTS: In the upper limb assessments, no main effects were found for the number of touches, but the exercise group showed a marginal increase over time on the left side. Error averages on the left side decreased significantly for the exercise group from baseline to 6 and 12 months. The exercise group also presented a lower Error CoV and the Reaction Time CoV increased on the right side. Significant findings for Fitts r on the left side indicated lower values for the exercise group, with improvements continuing at 12 months. CONCLUSION: We report the potential of global exercise interventions to facilitate improvements in reaction time and travel speed, as well as other motor control metrics, with lasting effects at 12 months, particularly on the non-dominant side.

Prospective Study of Non-Contrast, Abbreviated MRI for Hepatocellular Carcinoma Surveillance in Patients with Suboptimal Hepatic Visualisation on Ultrasound.

BACKGROUND: Biannual ultrasound (US) is recommended for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis. However, US has limited sensitivity for early-stage HCC, particularly in overweight cohorts, where hepatic visualisation is often inadequate. Currently there are no robust imaging surveillance strategies in patients with inadequate US visualisation. We investigated the ability of non-contrast, abbreviated magnetic resonance imaging (aMRI) to adequately visualise the liver for HCC surveillance in patients with previously inadequate US. METHODS: Patients undergoing US surveillance, where liver visualisation was inadequate (LI-RADS VIS-B and VIS-C), were prospectively recruited. Patients underwent non-contrast T2-weighted and diffusion-weighted aMRI. The images were reviewed and reported by an expert liver radiologist. Three independent, blinded radiologists assessed the aMRI visualisation quality using a binary score assessing five parameters (parenchymal definition, vascular definition, coverage of the liver, uniformity of liver appearance and signal-to-noise ratio). RESULTS: Thirty patients completed the aMRI protocol. The majority (90%) had underlying cirrhosis and were overweight (93.3%), with 50% obese and 20% severely obese. A total of 93.3% of the aMRI scans were of satisfactory quality. Six patients (20%) had hepatic abnormalities detected with aMRI that were not seen on their US: one HCC, one haemangioma and three clinically insignificant lesions. For the aMRI visualisation quality assessment, the coverage of the liver, vascular definition and parenchymal definition were consistently rated to be of sufficient quality by all three radiologists. CONCLUSIONS: Non-contrast aMRI provided good visualisation of the liver and detection of abnormalities in patients with inadequate US. aMRI should be further explored in a larger, prospective study as an alternative surveillance strategy in patients with inadequate US.

Corrigendum: Motor learning in developmental coordination disorder: behavioral and neuroimaging study.

[This corrects the article DOI: 10.3389/fnins.2023.1187790.].

The Relationship Between Motor Competence Physical Activity Cardiorespiratory Fitness and BMI in UK Adolescents.

Purpose: This study set out to identify the extent of the relationships between subsections of the Movement Assessment Battery for Children 2nd Edition - MABC2 (manual dexterity, aiming and catching, and balance) to PA, CRF and BMI in adolescents. Methods: Height, BMI, the MABC2, a 20m shuttle run test and wrist-worn accelerometery PA levels (mins) were measured. Multivariable linear regression models, adjusting for sex, height and BMI were used to assess the relationship of the three subsections of the MABC2 with PA, CRF and BMI. Results: A total of 155 adolescents, aged 13-14 years, took part in this study (77 girls, 78 boys). Balance reported significant relationships with moderate to vigorous PA (unstandardised Beta B=0.15, 95%CI 0.02-0.28), vigorous PA (B=0.06, 95%CI 0.02-0.09) and BMI (B=-0.01, 95%CI -0.02-0.005). Balance in addition to aiming and catching skills were both significantly related to adolescent CRF (B=0.30, 95%CI 0.17-0.42 and B=0.29, 95%CI 0.14-0.45, respectively). Conclusion: This study suggests that balance is the strongest correlate skill to achieving the highest intensities of PA and healthier BMI status in adolescents. .

Motor learning in developmental coordination disorder: behavioral and neuroimaging study.

Developmental coordination disorder (DCD) is characterized by motor learning deficits that are poorly understood within whole-body activities context. Here we present results of one of the largest non-randomized interventional trials combining brain imaging and motion capture techniques to examine motor skill acquisition and its underpinning mechanisms in adolescents with and without DCD. A total of 86 adolescents with low fitness levels (including 48 with DCD) were trained on a novel stepping task for a duration of 7 weeks. Motor performance during the stepping task was assessed under single and dual-task conditions. Concurrent cortical activation in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS). Additionally, structural and functional magnetic resonance imaging (MRI) was conducted during a similar stepping task at the beginning of the trial. The results indicate that adolescents with DCD performed similarly to their peers with lower levels of fitness in the novel stepping task and demonstrated the ability to learn and improve motor performance. Both groups showed significant improvements in both tasks and under single- and dual-task conditions at post-intervention and follow-up compared to baseline. While both groups initially made more errors in the Stroop task under dual-task conditions, at follow-up, a significant difference between single- and dual-task conditions was observed only in the DCD group. Notably, differences in prefrontal activation patterns between the groups emerged at different time points and task conditions. Adolescents with DCD exhibited distinct prefrontal activation responses during the learning and performance of a motor task, particularly when complexity was increased by concurrent cognitive tasks. Furthermore, a relationship was observed between MRI brain structure and function measures and initial performance in the novel stepping task. Overall, these findings suggest that strategies that address task and environmental complexities, while simultaneously enhancing brain activity through a range of tasks, offer opportunities to increase the participation of adolescents with low fitness in physical activity and sports.

Learning a novel rhythmic stepping task in children with probable developmental coordination disorder.

BACKGROUND: Developmental coordination disorder affects approximately 6% of children, interfering with participation in physical activity and can persist through adulthood. However, no studies have investigated the neuromotor mechanisms of learning of a novel task with rhythmic cueing. METHODS: Movement Assessment Battery for Children-2nd edition was used to identify 48 children with probable developmental coordination disorder (13.9 ± 0.05 yrs., 27% male) and 37 typically developed (13.9 ± 0.10 yrs., 54% male). While instrumented with an inertial measurement unit, both groups performed a novel rhythmic stepping task and with a concurrent auditory stroop test (dual-task), underwent seven weeks of intervention with step training with rhythmic cuing and were tested for retention five weeks post-intervention. FINDINGS: Initially, the group with probable developmental coordination disorder had a higher variability of step timing (coefficient of variation: 0.08 ± 0.003-typically developed - 0.09 ± 0.004-probable developmental coordination disorder, p < 0.05) and a frequency of peak power spectral density further from the target 0.5 Hz (0.50 ± 0.002 Hz-typically developed - 0.51 ± 0.003 Hz-probable developmental coordination disorder, p < 0.05), and were more affected by the dual-task: power spectral density at 0.5 Hz (-7.2 ± 3.3%-typically developed - -13.4 ± 4.6%- prob_DCD, p < 0.05) and stroop test errors (6.4 ± 1.1%-typically developed - -11.1 ± 2.4%- probable developmental coordination disorder, p < 0.05). The intervention led to similar improvements in both groups in coefficient of variation of step timing (0.12 ± 0.01-Pre - 0.07 ± 0.002-Post, p < 0.05), frequency of the peak power spectral density (0.51 ± 0.005 Hz-Pre - 0.50 ± 0.001 Hz-Post, p < 0.05) and relative power spectral density bandpower (3.2 ± 0.2%-Pre - 5.9 ± 0.3%-Post, p < 0.05). All improvements were retained after five weeks post-training. INTERPRETATION: Rhythmic cueing shows strong promise for enhancing motor learning in children with probable developmental coordination disorder. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov with reference: NCT03150784.

ArTisaN trial protocol: a single Centre, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs).

BACKGROUND: Neuroendocrine neoplasias (NENs) are a rare type of malignancy that arise from the cells of the neuroendocrine system. Most patients present with advanced, unresectable disease, typically with metastases to the liver. The presence of liver metastases dictates prognosis and there has been a number of studies investigating therapies that reduce the burden of liver disease. Selective Internal Radiation Therapy (SIRT) allows the delivery of targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Here, we describe the design and rationale of ArtTisaN, a phase II study to assess efficacy and tolerability of SIRT using TheraSpheres for the management of liver metastases secondary to NENs. METHODS: Twenty-four eligible participants will be recruited to receive SIRT with TheraSpheres. The primary objective is to determine the objective response rate to treatment, defined as the rate of best overall response in the treated liver volume. In addition, total hepatic response and overall response will be assessed according to RECIST 1.1. The second co-primary objective is to determine the incidence of adverse and serious adverse device events. The secondary objectives are progression free survival, overall survival and quality of life. Additional exploratory objectives include investigation of circulating biomarkers of response and identification of a radiomic signature of response. DISCUSSION: This trial will provide prospective evidence on the efficacy of SIRT using TheraSpheres for the management of liver metastases. TRIAL REGISTRATION: NCT04362436 .

Neuroergonomic assessment of developmental coordination disorder.

Until recently, neural assessments of gross motor coordination could not reliably handle active tasks, particularly in realistic environments, and offered a narrow understanding of motor-cognition. By applying a comprehensive neuroergonomic approach using optical mobile neuroimaging, we probed the neural correlates of motor functioning in young people with Developmental Coordination Disorder (DCD), a motor-learning deficit affecting 5-6% of children with lifelong complications. Neural recordings using fNIRS were collected during active ambulatory behavioral task execution from 37 Typically Developed and 48 DCD Children who performed cognitive and physical tasks in both single and dual conditions. This is the first of its kind study targeting regions of prefrontal cortical dysfunction for identification of neuropathophysiology for DCD during realistic motor tasks and is one of the largest neuroimaging study (across all modalities) involving DCD. We demonstrated that DCD is a motor-cognitive disability, as gross motor /complex tasks revealed neuro-hemodynamic deficits and dysfunction within the right middle and superior frontal gyri of the prefrontal cortex through functional near infrared spectroscopy. Furthermore, by incorporating behavioral performance, decreased neural efficiency in these regions were revealed in children with DCD, specifically during motor tasks. Lastly, we provide a framework, evaluating disorder impact in ecologically valid contexts to identify when and for whom interventional approaches are most needed and open the door for precision therapies.

Declining fitness and physical education lessons in UK adolescents.

OBJECTIVES: The objective was to determine recent cross-sectional trends in health-related fitness (HRF) in secondary school students by studying the 13-14 years old age group repeatedly over 6 years, considering parallel national trends in physical education (PE). METHODS: Height, weight, broad jump, grip strength, 20 m shuttle run and throwing and catching skills were measured by the same research team using standardised techniques from 2014 to 2019. Trends in these HRF measures were assessed by linear regression, adjusting for school, sex and height. Interactions with fitness and body mass index (BMI) were tested. The number of PE lessons reported in the UK Annual School Workforce Census between 2010 and 2019 for all state-funded secondary schools was analysed. RESULTS: Grip strength (B=-0.60, 95% CI -0.78 to -0.41), broad jump (B=-1.16, 95% CI -1.99 to -0.34), 20 m shuttle run (B=-1.85, 95% CI -2.58 to -1.12) and throwing and catching skills (B=-0.12, 95% CI -0.15 to -0.08) declined significantly over the study period. There was a greater reduction in broad jump and grip strength in adolescents with low fitness and a greater reduction in fitness and motor competence in adolescents with normal BMI. These declines coincided with a 16% reduction nationally in secondary school PE between 2010 (333 800 hours) and 2019 (280 725 hours). CONCLUSION: Adolescent HRF has declined in recent years, in parallel with PE lessons. Declines were observed across all young people and particularly those of low fitness and normal BMI. To reach the majority of young people, policy makers could increase PE in schools to increase activity and prevent worsening fitness and health in future generations.

A cross sectional assessment of nutrient intake and the association of the inflammatory properties of nutrients and foods with symptom severity in a large cohort from the UK Multiple Sclerosis Registry.

To assess the intake of nutrients in people with multiple sclerosis (pwMS) compared to a control population, and to assess the pro/ anti-inflammatory properties of nutrients/ foods and their relationships with fatigue and quality of life. This was a cross sectional study in which 2410 pwMS (686 men; 1721 women, 3 n/a, mean age 53 (11 years)) provided dietary data using a food frequency questionnaire that was hosted on the MS Register for a period of 3 months and this was compared to a cohort of 24,852 controls (11,250 male, 13,602 female, mean age 59 years). Consent was implied by anonymously filling out the questionnaire. A Wilcoxon test was used to compare intake between pwMS and controls, and a bivariate analyses followed by chi2 test were undertaken to identify significance and the strength of the relationship between pro/anti-inflammatory dietary factors and fatigue and EQ-5D. Compared to controls, all nutrients were significantly lower in the MS group (P < .05). Bivariate associations showed a significant correlation between consuming fish and lower clinical fatigue (χ2(1) = 4.221, P< .05), with a very low association (φ (phi) = -0.051, P = .04. Positive health outcomes on the EQ-5D measures were associated with higher carotene, magnesium oily fish and fruits and vegetable and sodium consumption (P < .05). Fiber, red meat, and saturated fat (women only) consumption was associated with worse outcomes on the EQ-5D measures (P < .05). pwMS have different dietary intakes compared to controls, and this may be associated with worse symptoms.

Effects of gender, activity type, class location and class composition on physical activity levels experienced during physical education classes in British secondary schools: a pilot cross-sectional study.

BACKGROUND: Pupils in secondary schools do not meet the targets for physical activity levels during physical education (PE) sessions, and there is a lack of data on the vigorous physical activity domain (VPA) in PE known to be positively associated with cardio metabolic health While PE session intensity depends on a variety of factors, the large majority of studies investigating these factors have not taken into account the nested structure of this type of data set. Therefore, the aim of this study was to investigate the relationship between various factors (gender, activity type, class location and class composition) and various activity levels during PE classes in secondary schools, using a multi-level statistical approach. METHODS: Year eight (12-13 years old) adolescents (201 boys and 106 girls) from six schools were fitted with accelerometers during one PE session each, to determine the percentage (%) of the PE session time spent in sedentary (SPA), light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) intensity levels. Two- and three-level (pupils, n = 307; classes, n = 13, schools, n = 6) mixed-effect models were used to assess the relationship between accelerometer-measured physical activity levels (% of class time spent in various activity levels) and gender, activity type, class location and composition. RESULTS: Participants engaged in MVPA and VPA for 30.7 ± 1.2% and 11.5 ± 0.8% of PE classes, respectively. Overall, no significant association between gender or class composition and PA was shown. A significant relationship between activity type and PA was observed, with Artistic classes significantly less active than Fitness classes for VPA (5.4 ± 4.5 vs. 12.5 ± 7.1%, p = 0.043, d:1.19). We also found a significant association between class location and PA, with significantly less time spent in SPA (24.8 ± 4.8% vs. 30.0 ± 3.4%, p = 0.042, d:0.77) and significantly more time spent in VPA (12.4 ± 3.7% vs. 7.6 ± 2.0%, p = 0.022, d:1.93) and MVPA (32.3 ± 6.7% vs.24.8 ± 3.8%, p = 0.024, d:1.33) in outdoors vs. indoors classes. CONCLUSIONS: The results suggest that class location and activity type could be associated with the intensity of PA in PE. It is essential to take into account the clustered nature of this type of data in similar studies if the sample size allows it.

The effects of small-needle-knife therapy on pain and mobility from knee osteoarthritis: a pilot randomized-controlled study.

OBJECTIVE: To investigate the effect of small needle-knife therapy in people with painful knee osteoarthritis. DESIGN: Pilot randomised, controlled trial. SETTING: Rehabilitation hospital. SUBJECTS: In-patients with osteo-arthritis of the knee. INTERVENTIONS: Either 1 to 3 small needle-knife treatments over seven days or oral Celecoxib. All patients stayed in hospital three weeks, receiving the same mobility-focused rehabilitation. MEASURES: Oxford Knee Score (OKS), gait speed and kinematics were recorded at baseline, at three weeks (discharge) and at three-months (OKS only). Withdrawal from the study, and adverse events associated with the small needle knife therapy were recorded. RESULTS: 83 patients were randomized: 44 into the control group, of whom 10 were lost by three weeks and 12 at 3 months; 39 into the experimental group of whom eight were lost at three weeks and three months. The mean (SE) OKS scores at baseline were Control 35.86 (1.05), Exp 38.38 (0.99); at three weeks 26.64 (0.97) and 21.94 (1.23); and at three months 25.83 (0.91) and 20.48 (1.14) The mean (SE) gait speed at baseline was 1.07 (0.03) m/sec (Control) and 0.98 (0.03), and at three weeks was 1.14 (0.03) and 1.12 (0.03) (P < 0.05). Linear mixed model statistical analysis showed that the improvements in the experimental group were statistically significant for total OKS score at discharge and three months. CONCLUSIONS: Small needle-knife therapy added to standard therapy for patients with knee osteoarthritis, was acceptable, safe and reduced pain and improved global function on the Oxford Knee Score. Further research is warranted.

Diet quality in late midlife is associated with faster walking speed in later life in women, but not men: findings from a prospective British birth cohort.

Healthy diet has been linked to better age-related functioning, but evidence on the relationship of diet quality in late midlife and measures of physical capability in later life is limited. Research on potential sex differences in this relationship is scarce. The aim was to investigate the prospective association between overall diet quality, as assessed by the Healthy Eating Index-2015 (HEI-2015) at 60-64 years and measures of walking speed 7 years later, among men and women from the Insight 46, a neuroscience sub-study of the Medical Research Council National Survey of Health and Development. Diet was assessed at 60-64 years using 5-d food diaries, from which total HEI-2015 was calculated. At 69-71 years, walking speed was estimated during four 10-m walks at self-selected pace, using inertial measurement units. Multivariable linear regression models with sex as a modifier, controlling for age, follow-up, lifestyle, health/social variables and physical performance, were used. The final sample consists of 164 women and 167 men (n 331). Women had higher HEI-2015 and slower walking speed than men. A 10-point increase in HEI-2015 was associated with faster walking speed among women (B 0·024, 95 % CI 0·006, 0·043), but not men. The association remained significant in the multivariable model (B 0·021, 95 % CI 0·003, 0·040). In women, higher diet quality in late midlife is associated with faster walking speed. A healthy diet in late midlife is likely to contribute towards better age-related physical capability, and sex differences are likely to affect this relationship.

A Cross-Sectional Feasibility Study of Nutrient Intake Patterns in People With Parkinson's Compared to Government Nutrition Guidelines.

Background: Diet could have implications for disease progression and management in people with Parkinson's disease (PwP). However, the knowledge of diet intake patterns in PwP is limited.Objectives: We set out to assess the feasibility of collecting diet data in PwP to determine food and nutrient intake, in order to compare to national nutrition guidelines and thus understand the habits in this population.Methods: In this cross-sectional feasibility study, PwP were approached through local support groups throughout the Thames Valley and were asked to complete a Food Frequency Questionnaire. Eligibility criteria included a self-reported neurologist confirmed diagnosis of Parkinson's disease. Completeness of questionnaires was reported and 80% was considered appropriate for each measure including demographic information.Results: Response rate was 61% and missing data rate for the 121 returned questionnaires was 74%; however, of the 90 used for analysis there was 100% completion of the questionnaires. Compared to the UK government guidelines, protein was significantly higher for both males and females and fluid intake was lower for both genders (p < 0.001). There were several other differences in nutrient intake compared to guidelines.Conclusion: We observed high levels of engagement from PwP and found that assessing food and nutrient patterns in PwP was feasible. Importantly, the diet was generally healthy overall, yet there were specific nutrients that may affect medication metabolism in PwP that were found to be high. Therefore further research into this emerging and important area is warranted.

A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis.

The impact of flavonoids on fatigue has not been investigated in relapsing and remitting multiple sclerosis (RRMS). OBJECTIVE: To determine the feasibility and estimate the potential effect of flavonoid-rich cocoa on fatigue and fatigability in RRMS. METHODS: A randomised double-blind placebo-controlled feasibility study in people recently diagnosed with RRMS and fatigue, throughout the Thames Valley, UK (ISRCTN69897291). During a 6-week intervention participants consumed a high or low flavonoid cocoa beverage daily. Fatigue and fatigability were measured at three visits (weeks 0, 3 and 6). Feasibility and fidelity were assessed through recruitment and retention, adherence and a process evaluation. RESULTS: 40 people with multiple sclerosis (10 men, 30 women, age 44±10 years) were randomised and allocated to high (n=19) or low (n=21) flavonoid groups and included in analysis. Missing data were <20% and adherence to intervention of allocated individuals was >75%. There was a small effect on fatigue (Neuro-QoL: effect size (ES) 0.04, 95% CI -0.40 to 0.48) and a moderate effect on fatigability (6 min walk test: ES 0.45, 95% CI -0.18 to 1.07). There were seven adverse events (four control, three intervention), only one of which was possibly related and it was resolved. CONCLUSION: A flavonoid beverage demonstrates the potential to improve fatigue and fatigability in RRMS.

Evaluation of a smartwatch-based intervention providing feedback of daily activity within a research-naive stroke ward: a pilot randomised controlled trial.

BACKGROUND: The majority of stroke patients are inactive outside formal therapy sessions. Tailored activity feedback via a smartwatch has the potential to increase inpatient activity. The aim of the study was to identify the challenges and support needed by ward staff and researchers and to examine the feasibility of conducting a randomised controlled trial (RCT) using smartwatch activity monitors in research-naive rehabilitation wards. Objectives (Phase 1 and 2) were to report any challenges and support needed and determine the recruitment and retention rate, completion of outcome measures, smartwatch adherence rate, (Phase 2 only) readiness to randomise, adherence to protocol (intervention fidelity) and potential for effect. METHODS: First admission, stroke patients (onset < 4 months) aged 40-75, able to walk 10 m prior to stroke and follow a two-stage command with sufficient cognition and vision (clinically judged) were recruited within the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Phase 1: a non-randomised observation phase (to allow practice of protocol)-patients received no activity feedback. Phase 2: a parallel single-blind pilot RCT. Patients were randomised into one of two groups: to receive daily activity feedback over a 9-h period or to receive no activity feedback. EQ-5D-5L, WHODAS and RMI were conducted at baseline, discharge and 3 months post-discharge. Descriptive statistics were performed on recruitment, retention, completion and activity counts as well as adherence to protocol. RESULTS: Out of 470 ward admissions, 11% were recruited across the two phases, over a 30-week period. Retention rate at 3 months post-discharge was 48%. Twenty-two percent of patients dropped out post-baseline assessment, 78% completed baseline and discharge admissions, from which 62% were assessed 3 months post-discharge. Smartwatch data were received from all patients. Patients were correctly randomised into each RCT group. RCT adherence rate to wearing the smartwatch was 80%. Baseline activity was exceeded for 65% of days in the feedback group compared to 55% of days in the no feedback group. CONCLUSIONS: Delivery of a smartwatch RCT is feasible in a research-naive rehabilitation ward. However, frequent support and guidance of research-naive staff are required to ensure completeness of clinical assessment data and protocol adherence. TRIALS REGISTRATION: ClinicalTrials.gov Identifier, NCT02587585-30th September 2015.

Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial.

BACKGROUND: Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate if inhaled furosemide relieves the air hunger component (uncomfortable urge to breathe) but not the sense of breathing work/effort of dyspnoea. METHODS: A randomised, double blind, placebo-controlled crossover trial in 16 healthy volunteers studied in a university research laboratory. Each participant received 3 mist inhalations (either 40 mg furosemide or 4 ml saline) separated by 30-60 min on 2 test days. Each participant was randomised to mist order 'furosemide-saline-furosemide' (n- = 8) or 'saline-furosemide-saline' (n = 8) on both days. One day involved hypercapnic air hunger tests (mean ± SD PCO2 = 50 ± 3.7 mmHg; constrained ventilation = 9 ± 1.5 L/min), the other involved work/effort tests with targeted ventilation (17 ± 3.1 L/min) and external resistive load (20cmH2O/L/s). Primary outcome was ratings of air hunger or work/effort every 15 s on a visual analogue scale. During saline inhalations, 1.5 mg furosemide was infused intravenously to match the expected systemic absorption from the lungs when furosemide is inhaled. Corresponding infusions of saline during furosemide inhalations maintained procedural blinding. Average visual analogue scale ratings (%full scale) during the last minute of air hunger or work/effort stimuli were analysed using Linear Mixed Methods. RESULTS: Data from all 16 participants were analysed. Inhaled furosemide relative to inhaled saline significantly improved visual analogues scale ratings of air hunger (Least Squares Mean ± SE - 9.7 ± 2%; p = 0.0015) but not work/effort (+ 1.6 ± 2%; p = 0.903). There were no significant adverse events. CONCLUSIONS: Inhaled furosemide was effective at relieving laboratory induced air hunger but not work/effort in healthy adults; this is consistent with the notion that modulation of pulmonary stretch receptor feedback by inhaled furosemide leads to dyspnoea relief that is specific to air hunger, the most unpleasant quality of dyspnoea. FUNDING: Oxford Brookes University Central Research Fund. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02881866 . Retrospectively registered on 29th August 2018.

Do Maternal Dietary Antioxidants Modify the Relationship Between Binge Drinking and Small for Gestational Age? Findings from a Longitudinal Cohort Study.

BACKGROUND: Vitamin C, vitamin E, and carotenoids are potent dietary antioxidants that have been shown to attenuate ethanol-induced harm in animal models of fetal alcohol spectrum disorders. A diet low in antioxidant-rich foods may induce a state of oxidative stress in the context of maternal alcohol consumption during pregnancy, potentially causing growth restriction in the developing fetus. METHODS: We conducted a secondary analysis of a longitudinal U.K. birth cohort. The sample comprised 9,699 women and their babies in Avon, U.K., with an estimated delivery date between April 1, 1991 and December 31, 1992. Alcohol consumption data were self-reported at 18 weeks' gestation via a postal questionnaire. Women reported any binge drinking (≥4 U.K. units/occasion) during the past month. Dietary data were self-reported at 32 weeks' gestation using a food frequency questionnaire. Estimated intakes of vitamins C and E and carotenoids were categorized into quartiles. Logistic regression models with interaction terms were used to investigate relationships between maternal binge drinking, dietary antioxidants, and fetal growth. Models were adjusted for maternal sociodemographic and lifestyle characteristics. Small for gestational age (SGA; <10th percentile) was defined using customized birth centiles. RESULTS: In the unadjusted models, binge drinking was associated with higher risk of SGA birth (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10, 1.72, p = 0.005), and higher maternal intakes of vitamin C (OR = 0.90, 95% CI 0.84, 0.96, p = 0.002) and vitamin E (OR = 0.90, 95% CI 0.84, 0.95, p < 0.0001) were associated with lower risk of SGA birth. However, addition of potentially confounding variables attenuated these relationships. Likelihood ratio tests indicated that interaction terms were not significant for vitamin C (p = 0.116), vitamin E (p = 0.059), or carotenoid intakes (p = 0.174). CONCLUSIONS: There was no evidence of maternal intake of dietary antioxidants modifying the relationship between maternal binge drinking and SGA birth.

The impact of high and low-intensity exercise in adolescents with movement impairment.

Five to six percent of young people have movement impairment (MI) associated with reduced exercise tolerance and physical activity levels which persist into adulthood. To better understand the exercise experience in MI, we determined the physiological and perceptual responses during and following a bout of exercise performed at different intensities typically experienced during sport in youth with MI. Thirty-eight adolescents (11-18 years) categorised on the Bruininks-Oseretsky Test of Motor Proficiency-2 Short-Form performed a peak oxygen uptake bike test ([Formula: see text]) test at visit 1 (V1). At visits 2 (V2) and 3 (V3), participants were randomly assigned to both low-intensity (LI) 30min exercise at 50% peak power output (PPO50%) and high-intensity (HI) 30s cycling at PPO100%, interspersed with 30s rest, for 30min protocol (matched for total work). Heart rate (HR) and rating of perceived exertion (RPE) for legs, breathing and overall was measured before, during and at 1, 3 and 7-min post-exercise (P1, P3, P7). There was a significant difference in [Formula: see text] between groups (MI:31.5±9.2 vs. NMI:40.0±9.5ml⋅kg-1⋅min-1, p<0.05). PPO was significantly lower in MI group (MI:157±61 vs. NMI:216±57 W)(p<0.05). HRavg during HI-cycling was reduced in MI (140±18 vs. 157±14bpm, p<0.05), but not LI (133±18 vs. 143±17bpm, p>0.05). Both groups experienced similar RPE for breathing and overall (MI:7.0±3.0 vs. NMI:6.0±2.0, p>0.05) at both intensities, but reported higher legs RPE towards the end (p<0.01). Significant differences were found in HRrecovery at P1 post-HI (MI:128±25.9 vs. NMI:154±20.2, p<0.05) but not for legs RPE. Perceived fatigue appears to limit exercise in youth with MI in both high and low-intensity exercise types. Our findings suggest interventions reducing perceived fatigue during exercise may improve exercise tolerance and positively impact on engagement in physical activities.

Does feedback on daily activity level from a Smart watch during inpatient stroke rehabilitation increase physical activity levels? Study protocol for a randomized controlled trial.

BACKGROUND: Practicing activities improves recovery after stroke, but many people in hospital do little activity. Feedback on activity using an accelerometer is a potential method to increase activity in hospital inpatients. This study's goal is to investigate the effect of feedback, enabled by a Smart watch, on daily physical activity levels during inpatient stroke rehabilitation and the short-term effects on simple functional activities, primarily mobility. METHODS/DESIGN: A randomized controlled trial will be undertaken within the stroke rehabilitation wards of the Second Affiliated hospital of Anhui University of Traditional Chinese Medicine, Hefei, China. The study participants will be stroke survivors who meet inclusion criteria for the study, primarily: able to participate, no more than 4 months after stroke and walking independently before stroke. Participants will all receive standard local rehabilitation and will be randomly assigned either to receive regular feedback about activity levels, relative to a daily goal tailored by the smart watch over five time periods throughout a working day, or to no feedback, but still wearing the Smart watch. The intervention will last up to 3 weeks, ending sooner if discharged. The data to be collected in all participants include measures of daily activity (Smart watch measure); mobility (Rivermead Mobility Index and 10-metre walking time); independence in personal care (Barthel Activities of Daily Living (ADL) Index); overall activities (the World Health Organization (WHO) Disability Assessment Scale, 12-item version); and quality of life (the Euro-Qol 5L5D). Data will be collected by assessors blinded to allocation of the intervention at baseline, 3 weeks or at discharge (whichever is the sooner); and a reduced data set will be collected at 12 weeks by telephone interview. The primary outcome will be change in daily accelerometer activity scores. Secondary outcomes are compliance and adherence to wearing the watch, and changes in mobility, independence in personal care activities, and health-related quality of life. DISCUSSION: This project is being implemented in a large city hospital with limited resources and limited research experience. There has been a pilot feasibility study using the Smart watch, which highlighted some areas needing change and these are incorporated in this protocol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02587585 . Registered on 30 September 2015. Chinese Clinical Trial Registry, ChiCTR-IOR-15007179 . Registered on 8 August 2015.