Assessing proprioception in children with upper motor neuron lesions: feasibility, validity, and reliability of the proprioception measurement tool.

Introduction: To investigate the feasibility, discriminative and convergent validity, and reliability of a lower limb sensor-based proprioception measure in children with upper motor neuron (UMN) lesions.

Method: We assessed three proprioception modalities (joint movement, joint position, and dynamic position sense) of the lower limbs in 49 children with UMN lesions and 50 typically developing (TD) peers (5-19 years). Forty-three children with UMN lesion had a congenital and six an acquired brain lesion and 82% were able to walk without a walking aid.

WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation.

One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12-ATG5-ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation.

Are tactile function and body awareness of the foot related to motor outcomes in children with upper motor neuron lesions?

Introduction: Somatosensory function can be reduced in children with Upper Motor Neuron (UMN) lesions. Therefore, we investigated relationships between somatosensory functions of the foot and motor outcomes in children with UMN lesions.

Method: In this cross-sectional study, we assessed the Tactile Threshold (TT) with monofilaments and body awareness with Tactile Localisation Tasks for spatial-related action (TLT) and structural-related perception (TLT) body representation at the foot sole.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency.

Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l).

Use of a wearable accelerometer to evaluate physical frailty in people receiving haemodialysis.

Background: Physical frailty is a major health concern among people receiving haemodialysis (HD) for stage-5 chronic kidney disease (CKD-5). Wearable accelerometers are increasingly being recommended to objectively monitor activity levels in CKD-5 and recent research suggests they may also represent an innovative strategy to evaluate physical frailty in vulnerable populations. However, no study has yet explored whether wearable accelerometers may be utilised to assess frailty in the context of CKD-5-HD.

Feasibility of randomized controlled trials and long-term implementation of interventions: Insights from a qualitative process evaluation of the PEDAL trial.

Introduction: A multi-site randomized controlled trial was carried out between 2015 and 2019 to evaluate the impacts on quality of life of an intradialytic exercise programme for people living with chronic kidney disease. This included a qualitative process evaluation which gave valuable insights in relation to feasibility of the trial and of the intervention in the long-term. These can inform future clinical Trial design and evaluation studies.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

Background: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics.

Resistance Exercise in People With Stage-3 Chronic Kidney Disease: Effects of Training Frequency (Weekly Volume) on Measures of Muscle Wasting and Function.

Resistance training (RT) is a proven anabolic intervention in people living with and without chronic kidney disease (CKD). To date, there is a dearth of knowledge regarding the dose-response relationship of RT in the non-dialysis dependent CKD population. Therefore, we aimed to explore the effects of RT frequency (weekly volume) on established measures of muscle wasting and function in CKD.

Leisure Time Physical Activity in Children and Young People With Cerebral Palsy: A Population-Based Study.

Purpose: To describe leisure time physical activity in children and young people with cerebral palsy and identify barriers and facilitators to participation.

Methods: Leisure time physical activity participation was derived from a national cerebral palsy register and associated factors were analyzed. Barriers and facilitators to participation were investigated through a survey.

Validity and reliability of an electromyography-based similarity index to quantify lower extremity selective voluntary motor control in children with cerebral palsy.

Objective: To quantify selective voluntary motor control (SVMC) objectively and more precisely, we combined the "Selective Control Assessment of the Lower Extremity" (SCALE) with surface electromyography. The resulting Similarity Index (SI) measures the similarity of muscle activation patterns. This study evaluated the preliminary validity and reliability of this novel SI measure in children with cerebral palsy (CP).

The ingenious ULKs: expanding the repertoire of the ULK complex with phosphoproteomics.

The mammalian ULK kinase complex is the most upstream component in the macroautophagy/autophagy signaling pathway. ULK1 and homolog ULK2, the sole serine/threonine kinases in autophagy, transduce an array of autophagy-inducing stimuli to downstream autophagic machinery, regulating autophagy from autophagosome initiation to fusion of autophagosomes with lysosomes. ULK signaling is also implicated in a diverse array of non-canonical processes from necroptosis to ER-Golgi trafficking to stress granule clearance.

Randomized Trial-PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis.

Introduction: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program.

Methods: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]).

Screening tools to expedite assessment of frailty in people receiving haemodialysis: a diagnostic accuracy study.

Background: Frailty is associated with multiple adverse outcomes in stage-5 chronic kidney disease (CKD-5) and upwards of one third of people receiving haemodialysis (HD) are frail. While many frailty screening methods are available in both uremic and non-uremic populations, their implementation in clinical settings is often challenged by time and resource constraints. In this study, we explored the diagnostic accuracy of time-efficient screening tools in people receiving HD.

Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT.

Background: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown.

Objectives: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients.

Design: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis.

Phosphoproteomic identification of ULK substrates reveals VPS15-dependent ULK/VPS34 interplay in the regulation of autophagy.

Autophagy is a process through which intracellular cargoes are catabolised inside lysosomes. It involves the formation of autophagosomes initiated by the serine/threonine kinase ULK and class III PI3 kinase VPS34 complexes. Here, unbiased phosphoproteomics screens in mouse embryonic fibroblasts deleted for Ulk1/2 reveal that ULK loss significantly alters the phosphoproteome, with novel high confidence substrates identified including VPS34 complex member VPS15 and AMPK complex subunit PRKAG2.

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

Background: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK.

Methods: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD.

Validity and reliability of high-resolution ultrasound imaging for the assessment of regional body composition in stage 5 chronic kidney disease patients undergoing continuous ambulatory peritoneal dialysis.

Background: Accurate measurement of muscle mass is an important research and clinical tool. High-resolution ultrasound (US) has shown potential as a method to assess muscle and fat mass at specific anatomical sites. However, there is limited evidence for the reliability of US to measure muscle size in patients receiving continuous ambulatory peritoneal dialysis (CAPD).

Exercise-induced changes in gait kinematics in multiple sclerosis with minimal neurological disability.

Background: Exercise-induced gait deterioration is a frequently encountered symptom that limits ambulation throughout the clinical course, becoming more prominent with increasing neurological disability in people with MS (pwMS).

Objective: We attempted to objectively document exercise-induced gait changes in pwMS with minimal neurological disability and stable disease.

Methods: Gait kinematics and spatio-temporal parameters were recorded using 3D motion analysis before and after a 20-minute treadmill walk (Group A, n=15)/run (Group B, n=15) at a self-selected speed in pwMS and compared with healthy controls (n=15).

Association of postural balance and falls in adult patients receiving haemodialysis: A prospective cohort study.

Background: Static postural balance performance is often impaired in people receiving haemodialysis (HD) for the treatment of stage-5 chronic kidney disease (CKD-5). However, the question as to whether lower postural balance is associated with adverse clinical outcomes such as falls has not been addressed yet.

Research Question: We conducted a prospective cohort study to explore the association between static postural balance and falls in people receiving HD.

Minimum accelerometer wear-time for reliable estimates of physical activity and sedentary behaviour of people receiving haemodialysis.

Background: Low levels of physical activity are implicated in low life expectancies of people receiving maintenance haemodialysis. Accelerometers are increasingly being used to quantify activity behaviours of this population but guidance to quality-assure such data is lacking. The objective of this study was to provide data processing and reduction recommendations to ensure accelerometer-derived outcomes are sufficiently reliable for interpretative analysis.

The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: a prospective cohort study.

Background: Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling.

Test-retest reliability and minimal detectable change of ankle kinematics and spatiotemporal parameters in MS population.

Background: Many people with multiple sclerosis (pwMS) experience walking impairments often including foot drop, evident as either reduced dorsiflexion at initial contact and/or at the swing phase of the gait cycle. To measure even subtle differences in ankle kinematics, 3D gait analysis is considered a 'gold' standard. However, the psychometric properties of ankle kinematics in the MS population have not yet been examined.

Baroreflex function, haemodynamic responses to an orthostatic challenge, and falls in haemodialysis patients.

Background: Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients.

Ankle Kinematics and Temporal Gait Characteristics over the Duration of a 6-Minute Walk Test in People with Multiple Sclerosis Who Experience Foot Drop.

Foot drop is a common gait impairment in people with MS (pwMS) but in some foot drop may only occur after a period of prolonged walking and may be a sign of motor fatigability. The purpose of the study was to explore whether, for pwMS, an adapted six-minute walk test (6minWT) would result in an increase in foot drop as measured using electrogoniometry. Sagittal ankle kinematics were recorded for fifteen participants (10 females and 5 males, aged 37-64) with MS (EDSS 4-6) throughout the 6minWT.