Effects of wrist posture and stabilization on precision grip force production and muscle activation patterns.

Most of the power for generating forces in the fingers arises from muscles located in the forearm. This configuration maximizes finger joint range of motion while minimizing finger mass and inertia. The resulting multiarticular arrangement of the tendons, however, complicates independent control of the wrist and the digits. Actuating the wrist impacts sensorimotor control of the fingers and vice versa. The goal of this study was to systematically investigate interactions between isometric wrist and digit control. Specifically, we examined how the need to maintain a specified wrist posture influences precision grip. Fifteen healthy adults produced maximum precision grip force at 11 different wrist flexion/extension angles, with the arm supported, under two conditions: 1) the participant maintained the desired wrist angle while performing the precision grip and 2) a robot maintained the specified wrist angle. Wrist flexion/extension posture significantly impacted maximum precision grip force (P < 0.001), with the greatest grip force achieved when the wrist was extended 30° from neutral. External wrist stabilization by the robot led to a 20% increase in precision grip force across wrist postures. Increased force was accompanied by increased muscle activation but with an activation pattern similar to the one used when the participant had to stabilize their wrist. Thus, simultaneous wrist and finger requirements impacted performance of an isometric finger task. External wrist stabilization can promote increased precision grip force resulting from increased muscle activation. These findings have potential clinical significance for individuals with neurologically driven finger weakness, such as stroke survivors.NEW & NOTEWORTHY We explored the interdependence between wrist and fingers by assessing the influence of wrist posture and external stabilization on precision grip force generation. We found that maximum precision grip force occurred at an extended wrist posture and was 20% greater when the wrist was Externally Stabilized. The latter resulted from amplification of muscle activation patterns from the Self-Stabilized condition rather than adoption of new patterns exploiting external wrist stabilization.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society-Unified Parkinson's Disease Rating Scale items (rho: 0.12-0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Wastewater microorganisms impact the micropollutant biotransformation potential of natural stream biofilms.

Biotransformation is the most important process removing manmade chemicals from the environment, yet mechanisms governing this essential ecosystem function are underexplored. To understand these mechanisms, we conducted experiments in flow-through systems, by colonizing stream biofilms under different conditions of mixing river water with treated (and ultrafiltered) wastewater. We performed biotransformation experiments with those biofilms, using a set of 75 micropollutants, and could disentangle potential mechanisms determining the biotransformation potential of stream biofilms. We showed that the increased biotransformation potential downstream of wastewater treatment plants that we observed for specific micropollutants contained in household wastewaters (downstream effect) is caused by microorganisms released with the treated effluent, rather than by the in-stream exposure to those micropollutants. Complementary data from 16S rRNA amplicon-sequencing revealed 146 amplicon sequence variants (ASVs) that followed the observed biotransformation patterns. Our results align with findings for community tolerance, and provide clear experimental evidence that microorganisms released with treated wastewater integrate into downstream biofilms and impact crucial ecosystem functions.

Accelerated Muscle Deoxygenation in Aerobically Fit Subjects During Exhaustive Exercise Is Associated With the ACE Insertion Allele.

Introduction: The insertion/deletion (I/D) polymorphism in the gene for the major regulator of vascular tone, angiotensin-converting enzyme-insertion/deletion (ACE-I/D) affects muscle capillarization and mitochondrial biogenesis with endurance training. We tested whether changes of leg muscle oxygen saturation (SmO2) during exhaustive exercise and recovery would depend on the aerobic fitness status and the ACE I/D polymorphism. Methods: In total, 34 healthy subjects (age: 31.8 ± 10.2 years, 17 male, 17 female) performed an incremental exercise test to exhaustion. SmO2 in musculus vastus lateralis (VAS) and musculus gastrocnemius (GAS) was recorded with near-IR spectroscopy. Effects of the aerobic fitness status (based on a VO2peak cutoff value of 50 ml O2 min-1 kg-1) and the ACE-I/D genotype (detected by PCR) on kinetic parameters of muscle deoxygenation and reoxygenation were assessed with univariate ANOVA. Results: Deoxygenation with exercise was comparable in VAS and GAS (p = 0.321). In both leg muscles, deoxygenation and reoxygenation were 1.5-fold higher in the fit than the unfit volunteers. Differences in muscle deoxygenation, but not VO2peak, were associated with gender-independent (p > 0.58) interaction effects between aerobic fitness × ACE-I/D genotype; being reflected in a 2-fold accelerated deoxygenation of VAS for aerobically fit than unfit ACE-II genotypes and a 2-fold higher deoxygenation of GAS for fit ACE-II genotypes than fit D-allele carriers. Discussion: Aerobically fit subjects demonstrated increased rates of leg muscle deoxygenation and reoxygenation. Together with the higher muscle deoxygenation in aerobically fit ACE-II genotypes, this suggests that an ACE-I/D genotype-based personalization of training protocols might serve to best improve aerobic performance.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

[Neurological manifestations in pediatric patients with COVID-19: case report]. / Manifestaciones neurológicas en pacientes pediátricos con COVID-19: reporte de casos.

The COVID-19 pandemic currently affects millions of people including the pediatric population. The clinical manifestations in children are diverse: respiratory, gastrointestinal, hematological, neurological and systemic. In order to describe the various clinical and neurological manifestations during the evolution of the disease, we documented a series of cases of pediatric patients with COVID-19. Various mechanisms are proposed through which SARS-CoV-2 would cause neurological injury (direct injury, secondary to an immune response, among others) with variable clinical characteristics (seizures, muscle weakness, sensorial disorder). Studies on clinical characteristics and prognostic factors in children and adolescents with SARS-CoV-2 are limited, therefore, this report provides a spectrum of neurological manifestations associated with SARS-CoV-2 in pediatric population.

La pandemia por la COVID-19 afecta actualmente a millones de personas sin exceptuar la población pediátrica. Las manifestaciones clínicas en niños son variables: respiratorias, gastrointestinales, hematológicas, neurológicas y sistémicas. Con el objetivo de describir las diversas presentaciones clínicas y neurológicas durante la evolución de la enfermedad se documentó una serie de casos de pacientes pediátricos con la COVID-19. Se plantean diversos mecanismos a través de los cuales el SARS-CoV-2 causaría daño neurológico (daño directo, secundario a respuesta inmune, entre otras) con características clínicas variables (convulsiones, debilidad muscular, trastorno del sensorio). Los estudios sobre características clínicas y factores pronósticos en niños y adolescentes con SARS-CoV-2 son limitados, por lo cual el presente reporte contribuye con un espectro de manifestaciones neurológicas asociadas al SARS-CoV-2 en población pediátrica.

[General palliative care during the pandemic]. / Allgemeine Palliativversorgung in Pandemiezeiten.

BACKGROUND: The German healthcare system is facing unprecedented challenges due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Palliative care for critically ill patients and their families was also severely compromised, especially during the first wave of the pandemic, in both inpatient and outpatient settings. MATERIALS AND METHODS: The paper is based on our experience in routine inpatient palliative care and partial results of a study conducted as part of the collaborative project "National Strategy for Palliative Care in Pandemic Times (PallPan)". Based on our experience from the inpatient care of patients suffering from severe or life-limiting disease, best-practice examples for improving or maintaining care in the on-going pandemic are described. RESULTS: Restrictive visitor regulations, communication barriers and insufficient possibilities to accompany dying patients or their grieving relatives continue to pose major challenges in general and specialized inpatient palliative care. In order to maintain high-quality palliative care, it is necessary to create structures that enable targeted therapy discussions and end-of-life care in the presence of relatives. Therefore, innovative communication methods like video calls or individualized exceptions from visitor restrictions are needed. CONCLUSIONS: Adequate care for seriously ill and dying patients and their relatives must be guaranteed during the pandemic. Individual arrangements should be arranged and implemented. If available, earlier involvement of specialized palliative care teams can be beneficial.

Micropollutant biotransformation and bioaccumulation in natural stream biofilms.

Micropollutants are ubiquitously found in natural surface waters and pose a potential risk to aquatic organisms. Stream biofilms, consisting of bacteria, algae and other microorganisms potentially contribute to bioremediating aquatic environments by biotransforming xenobiotic substances. When investigating the potential of stream biofilms to remove micropollutants from the water column, it is important to distinguish between different fate processes, such as biotransformation, passive sorption and active bioaccumulation. However, due to the complex nature of the biofilm community and its extracellular matrix, this task is often difficult. In this study, we combined biotransformation experiments involving natural stream biofilms collected up- and downstream of wastewater treatment plant outfalls with the QuEChERS extraction method to distinguish between the different fate processes. The QuEChERS extraction proved to be a suitable method for a broad range of micropollutants (> 80% of the investigated compounds). We found that 31 out of 63 compounds were biotransformed by the biofilms, with the majority being substitution-type biotransformations, and that downstream biofilms have an increased biotransformation potential towards specific wastewater-relevant micropollutants. Overall, using the experimental and analytical strategy developed, stream biofilms were demonstrated to have a broad inherent micropollutant biotransformation potential, and to thus contribute to bioremediation and improving ecosystem health.

Manifestaciones neurológicas en pacientes pediátricos con COVID-19: reporte de casos

La pandemia por la COVID-19 afecta actualmente a millones de personas sin exceptuar la población pediátrica. Las manifestaciones clínicas en niños son variables: respiratorias, gastrointestinales, hematológicas, neurológicas y sistémicas. Con el objetivo de describir las diversas presentaciones clínicas y neurológicas durante la evolución de la enfermedad se documentó una serie de casos de pacientes pediátricos con la COVID-19. Se plantean diversos mecanismos a través de los cuales el SARS-CoV-2 causaría daño neurológico (daño directo, secundario a respuesta inmune, entre otras) con características clínicas variables (convulsiones, debilidad muscular, trastorno del sensorio). Los estudios sobre características clínicas y factores pronósticos en niños y adolescentes con SARS-CoV-2 son limitados, por lo cual el presente reporte contribuye con un espectro de manifestaciones neurológicas asociadas al SARS-CoV-2 en población pediátrica.

The COVID-19 pandemic currently affects millions of people including the pediatric population. The clinical manifestations in children are diverse: respiratory, gastrointestinal, hematological, neurological and systemic. In order to describe the various clinical and neurological manifestations during the evolution of the disease, we documented a series of cases of pediatric patients with COVID-19. Various mechanisms are proposed through which SARS-CoV-2 would cause neurological injury (direct injury, secondary to an immune response, among others) with variable clinical characteristics (seizures, muscle weakness, sensorial disorder). Studies on clinical characteristics and prognostic factors in children and adolescents with SARS-CoV-2 are limited, therefore, this report provides a spectrum of neurological manifestations associated with SARS-CoV-2 in pediatric population.

Black-Silicon Ultraviolet Photodiodes Achieve External Quantum Efficiency above 130.

At present, ultraviolet sensors are utilized in numerous fields ranging from various spectroscopy applications via biotechnical innovations to industrial process control. Despite this, the performance of current UV sensors is surprisingly poor. Here, we break the theoretical one-photon-one-electron barrier and demonstrate a device with a certified external quantum efficiency above 130% in UV range without external amplification. The record high performance is obtained using a nanostructured silicon photodiode with self-induced junction. We show that the high efficiency is based on effective utilization of multiple carrier generation by impact ionization taking place in the nanostructures. While the results can readily have a significant impact on the UV-sensor industry, the underlying technological concept can be applied to other semiconductor materials, thereby extending above unity response to longer wavelengths and offering new perspectives for improving efficiencies beyond the Shockley-Queisser limit.

Age-Dependent Asymmetry of Wrist Position Sense Is Not Influenced by Stochastic Tactile Stimulation.

Stochastic stimulation has been shown to improve movement, balance, the sense of touch, and may also improve position sense. This stimulation can be non-invasive and may be a simple technology to enhance proprioception. In this study, we investigated whether sub-threshold stochastic tactile stimulation of mechanoreceptors reduces age-related errors in wrist position estimation. Fifteen young (24.5±1.5y) and 23 elderly (71.7±7.3y) unimpaired, right-handed adults completed a wrist position gauge-matching experiment. In each trial, the participant's concealed wrist was moved to a target position between 10 and 30° of wrist flexion or extension by a robotic manipulandum. The participant then estimated the wrist's position on a virtual gauge. During half of the trials, sub-threshold stochastic tactile stimulation was applied to the wrist muscle tendon areas. Stochastic stimulation did not significantly influence wrist position sense. In the elderly group, estimation errors decreased non-significantly when stimulation was applied compared to the trials without stimulation [mean constant error reduction Δ µ ( θ c o n o f ) = 0 . 8 ° in flexion and Δ µ ( θ c o n o e ) = 0 . 7 ° in extension direction, p = 0.95]. This effect was less pronounced in the young group [ Δ µ ( θ c o n y ) = 0 . 2 ° in flexion and in extension direction, p = 0.99]. These improvements did not yield a relevant effect size (Cohen's d < 0.1). Estimation errors increased with target angle magnitude in both movement directions. In young participants, estimation errors were non-symmetric, with estimations in flexion [ µ ( θ c o n y f ) = 1 . 8 ° , σ ( θ c o n y f ) = 7 . 0 ° ] being significantly more accurate than in extension [ µ ( θ c o n y e ) = 8 . 3 ° , σ ( θ c o n y e ) = 9 . 3 ° , p < 0.01]. This asymmetry was not present in the elderly group, where estimations in flexion [ µ ( θ c o n o f ) = 7 . 5 ° , σ ( θ c o n o f ) = 9 . 8 ° ] were similar to extension [ µ ( θ c o n o e ) = 7 . 7 ° , σ ( θ c o n o e ) = 9 . 3 ° ]. Hence, young and elderly participants performed equally in extension direction, whereas wrist position sense in flexion direction deteriorated with age (p < 0.01). Though unimpaired elderly adults did not benefit from stochastic stimulation, it cannot be deduced that individuals with more severe impairments of their sensory system do not profit from this treatment. While the errors in estimating wrist position are symmetric in flexion and extension in elderly adults, young adults are more accurate when estimating wrist flexion, an effect that has not been described before.

Wearable Sensors in Ambulatory Individuals With a Spinal Cord Injury: From Energy Expenditure Estimation to Activity Recommendations.

Inappropriate physical inactivity is a global health problem increasing the risk of cardiometabolic diseases. Wearable sensors show great potential to promote physical activity and thus a healthier lifestyle. While commercial activity trackers are available to estimate energy expenditure (EE) in non-disabled individuals, they are not designed for reliable assessments in individuals with an incomplete spinal cord injury (iSCI). Furthermore, activity recommendations for this population are currently rather vague and not tailored to their individual needs, and activity guidelines provided for the non-disabled population may not be easily translated for this population. However, especially in iSCI individuals with impaired abilities to stand and walk, the assessment of physical activities and appropriate recommendations for a healthy lifestyle are challenging. Therefore, the study aimed at developing an EE estimation model for iSCI individuals able to walk based on wearable sensor data. Additionally, the data collected within this study was used to translate common activity recommendations for the non-disabled population to easily understandable activity goals for ambulatory individuals with an iSCI. In total, 30 ambulatory individuals with an iSCI were equipped with wearable sensors while performing 12 different physical activities. EE was measured continuously and demographic and anthropometric variables, clinical assessment scores as well as wearable-sensor-derived features were used to develop different EE estimation models. The best EE estimation model comprised the estimation of resting EE using the updated Harris-Benedict equation, classifying activities using a k-nearest neighbor algorithm, and applying a multiple linear regression-based EE estimation model for each activity class. The mean absolute estimation error of this model was 15.2 ± 6.3% and the corresponding mean signed error was -3.4 ± 8.9%. Translating activity recommendations of global health institutions, we suggest a minimum of 2,000-3,000 steps per day for ambulatory individuals with an iSCI. If ambulatory individuals with an iSCI targeted the popular 10,000 steps a day recommendation for the non-disabled population, their equivalent would be around 8,000 steps a day. The combination of the presented dedicated EE estimation model for ambulatory individuals with an iSCI and the translated activity recommendations is an important step toward promoting an active lifestyle in this population.

Predicting upper limb compensation during prehension tasks in tetraplegic spinal cord injured patients using a single wearable sensor.

Upper limb (UL) compensation is a common strategy of patients with a high spinal cord injury (SCI), i.e., tetraplegic patients, to perform activities of daily living (ADLs) despite their sensorimotor deficits. Currently, an objective and sensitive tool to assess UL compensation, which is applicable in the clinical routine and in the daily life of patients, is missing. In this work, we propose a metric to quantify this compensation using a single inertial measurement unit (IMU). The spread of forearm pitch angles of an IMU attached to the wrist of 17 SCI patients and 18 healthy controls performing six prehension tasks of the graded redefined assessment of strength, sensibility and prehension (GRASSP) was extracted. Using the spread of the forearm pitch angles, a classification of UL compensation was possible with very good to excellent accuracies in all six different prehension tasks. Furthermore, the spread of forearm pitch angles correlated moderately to very strongly with qualitative and quantitative GRASSP prehension scores and the task duration. Therefore, we conclude that our proposed method has a high potential to classify compensation accurately and objectively and might be used to quantify the degree of UL compensation in ADLs. Thus, this method could be implemented in clinical trials investigating the effectiveness of interventions targeting UL functions.

Does electrical stimulation in the lower urinary tract increase urine production? A randomised comparative proof-of-concept study in healthy volunteers.

TRIAL DESIGN: During electrical stimulation in the lower urinary tract for the purpose of current perception threshold and sensory evoked potential recording, we observed that bladder volume increased rapidly. The aim of this prospective randomised comparative proof-of-concept study was to quantify urine production per time during stimulation of the lower urinary tract using different stimulation frequencies. METHODS: Ninety healthy subjects (18 to 36 years old) were included. Forty females and 50 males were randomly assigned to one of the following study groups: dome, trigone or proximal, membranous (males only) or distal urethra. Starting from 60mL prefilling, stimulation was performed at two separate visits with a 14 French custom-made catheter using randomly applied frequencies of 0.5Hz, 1.1Hz, 1.6Hz (each with 500 stimuli). After each stimulation cycle per frequency, urine production was assessed. Main outcome measures represented urine production during stimulation, daily life and their ratio. RESULTS: Lower urinary tract electrical stimulation increased urine production per time compared to bladder diary baseline values. Linear mixed model showed that frequency (p<0.001), stimulation order (p = 0.003), intensity (p = 0.042), and gender (p = 0.047) had a significant influence on urine production. Location, visit and age had no significant influence. CONCLUSIONS: Urine production is increased during electrical stimulation with a bigger impact of higher frequencies. This might be relevant for methodological aspects in the assessment of lower urinary tract afferent function and for patients with impaired renal urine output. Inhibition of renal sympathetic nerve activity by vagal afferents may be the underlying mechanism.

Concentric and Eccentric Pedaling-Type Interval Exercise on a Soft Robot for Stable Coronary Artery Disease Patients: Toward a Personalized Protocol.

BACKGROUND: Cardiovascular diseases are the leading causes of death worldwide, and coronary artery disease (CAD) is one of the most common causes of death in Europe. Leading cardiac societies recommend exercise as an integral part of cardiovascular rehabilitation because it reduces the morbidity and mortality of patients with CAD. Continuous low-intensity exercise using shortening muscle actions (concentric, CON) is a common training modality during cardiovascular rehabilitation. However, a growing clinical interest has been recently developed in high-intensity interval training (HIIT) for stable patients with CAD. Exercise performed with lengthening muscle actions (eccentric, ECC) could be tolerated better by patients with CAD as they can be performed with higher loads and lower metabolic cost than CON exercise. OBJECTIVE: We developed a clinical protocol on a soft robot to compare cardiovascular and muscle effects of repeated and work-matched CON versus ECC pedaling-type interval exercise between patients with CAD during cardiovascular rehabilitation. This study aims to ascertain whether the developed training protocols affect peak oxygen uptake (VO2peak), peak aerobic power output (Ppeak), and parameters of muscle oxygen saturation (SmO2) during exercise, and anaerobic muscle power. METHODS: We will randomize 20-30 subjects to either the CON or ECC group. Both groups will perform a ramp test to exhaustion before and after the training period to measure cardiovascular parameters and SmO2. Moreover, the aerobic skeletal muscle power (Ppeak) is measured weekly during the 8-week training period using a simulated squat jump and a counter movement jump on the soft robot and used to adjust the training load. The pedaling-type interval exercise on the soft robot is performed involving either CON or ECC muscle actions. The soft robotic device being used is a closed kinetic chain, force-controlled interactive training, and testing device for the lower extremities, which consists of two independent pedals and free footplates that are operated by pneumatic artificial muscles. RESULTS: The first patients with CAD, who completed the training, showed protocol-specific improvements, reflecting, in part, the lower aerobic training status of the patient completing the CON protocol. Rehabilitation under the CON protocol, more than under the ECC protocol, improved cardiovascular parameters, that is, VO2peak (+26% vs -6%), and Ppeak (+20% vs 0%), and exaggerated muscle deoxygenation during the ramp test (248% vs 49%). Conversely, markers of metabolic stress and recovery from the exhaustive ramp test improved more after the ECC than the CON protocol, that is, peak blood lactate (-9% vs +20%) and peak SmO2 (+7% vs -7%). Anaerobic muscle power only improved after the CON protocol (+18% vs -15%). CONCLUSIONS: This study indicates the potential of the implemented CON and ECC protocols of pedaling-type interval exercise to improve oxygen metabolism of exercised muscle groups while maintaining or even increasing the Ppeak. The ECC training protocol seemingly provided a lower cardiovascular stimulus in patients with CAD while specifically enhancing the reoxygenation and blood lactate clearance in recruited muscle groups during recovery from exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT02845063; https://clinicaltrials.gov/ct2/show/NCT02845063.

Altered T cell receptor beta repertoire patterns in pediatric ulcerative colitis.

The antigenic specificity of T cells occurs via generation and rearrangement of different gene segments producing a functional T cell receptor (TCR). High-throughput sequencing (HTS) allows in-depth assessment of TCR repertoire patterns. There are limited data concerning whether TCR repertoires are altered in inflammatory bowel disease. We hypothesized that pediatric ulcerative colitis (UC) patients possess unique TCR repertoires, resulting from clonotypical expansions in the gut. Paired blood and rectal samples were collected from nine newly diagnosed treatment-naive pediatric UC patients and four healthy controls. DNA was isolated to determine the TCR-ß repertoire by HTS. Significant clonal expansion was demonstrated in UC patients, with inverse correlation between clinical disease severity and repertoire diversity in the gut. Using different repertoire variables in rectal biopsies, a clear segregation was observed between patients with severe UC, those with mild-moderate disease and healthy controls. Moreover, the overlap between autologous blood-rectal samples in UC patients was significantly higher compared with overlap among controls. Finally, we identified several clonotypes that were shared in either all or the majority of UC patients in the colon. Clonal expansion of TCR-ß-expressing T cells among UC patients correlates with disease severity and highlights their involvement in mediating intestinal inflammation.

Estimation of Energy Expenditure in Wheelchair-Bound Spinal Cord Injured Individuals Using Inertial Measurement Units.

A healthy lifestyle reduces the risk of cardio-vascular disease. As wheelchair-bound individuals with spinal cord injury (SCI) are challenged in their activities, promoting and coaching an active lifestyle is especially relevant. Although there are many commercial activity trackers available for the able-bodied population, including those providing feedback about energy expenditure (EE), activity trackers for the SCI population are largely lacking, or are limited to a small set of activities performed in controlled settings. The aims of the present study were to develop and validate an algorithm based on inertial measurement unit (IMU) data to continuously monitor EE in wheelchair-bound individuals with a SCI, and to establish reference activity values for a healthy lifestyle in this population. For this purpose, EE was measured in 30 subjects each wearing four IMUs during 12 different physical activities, randomly selected from a list of 24 activities of daily living. The proposed algorithm consists of three parts: resting EE estimation based on multi-linear regression, an activity classification using a k-nearest-neighbors algorithm, and EE estimation based on artificial neural networks (ANNs). The mean absolute estimation error for the ANN-based algorithm was 14.4% compared to indirect calorimeter measurements. Based on reference values from the literature and the data collected within this study, we recommend wheeling 3 km per day for a healthy lifestyle in wheelchair-bound SCI individuals. Combining the proposed algorithm with a recommendation for physical activity provides a powerful tool for the promotion of an active lifestyle in the SCI population, thereby reducing the risk for secondary diseases.

Algorithm for improving psychophysical threshold estimates by detecting sustained inattention in experiments using PEST.

Psychophysical procedures are applied in various fields to assess sensory thresholds. During experiments, sampled psychometric functions are usually assumed to be stationary. However, perception can be altered, for example by loss of attention to the presentation of stimuli, leading to biased data, which results in poor threshold estimates. The few existing approaches attempting to identify non-stationarities either detect only whether there was a change in perception, or are not suitable for experiments with a relatively small number of trials (e.g., [Formula: see text] 300). We present a method to detect inattention periods on a trial-by-trial basis with the aim of improving threshold estimates in psychophysical experiments using the adaptive sampling procedure Parameter Estimation by Sequential Testing (PEST). The performance of the algorithm was evaluated in computer simulations modeling inattention, and tested in a behavioral experiment on proprioceptive difference threshold assessment in 20 stroke patients, a population where attention deficits are likely to be present. Simulations showed that estimation errors could be reduced by up to 77% for inattentive subjects, even in sequences with less than 100 trials. In the behavioral data, inattention was detected in 14% of assessments, and applying the proposed algorithm resulted in reduced test-retest variability in 73% of these corrected assessments pairs. The novel algorithm complements existing approaches and, besides being applicable post hoc, could also be used online to prevent collection of biased data. This could have important implications in assessment practice by shortening experiments and improving estimates, especially for clinical settings.

Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.

Reliability of Wearable-Sensor-Derived Measures of Physical Activity in Wheelchair-Dependent Spinal Cord Injured Patients.

Physical activity (PA) has been shown to have a positive influence on functional recovery in patients after a spinal cord injury (SCI). Hence, it can act as a confounder in clinical intervention studies. Wearable sensors are used to quantify PA in various neurological conditions. However, there is a lack of knowledge about the inter-day reliability of PA measures. The objective of this study was to investigate the single-day reliability of various PA measures in patients with a SCI and to propose recommendations on how many days of PA measurements are required to obtain reliable results. For this, PA of 63 wheelchair-dependent patients with a SCI were measured using wearable sensors. Patients of all age ranges (49.3 ± 16.6 years) and levels of injury (from C1 to L2, ASIA A-D) were included for this study and assessed at three to four different time periods during inpatient rehabilitation (2 weeks, 1 month, 3 months, and if applicable 6 months after injury) and after in-patient rehabilitation in their home-environment (at least 6 months after injury). The metrics of interest were total activity counts, PA intensity levels, metrics of wheeling quantity and metrics of movement quality. Activity counts showed consistently high single-day reliabilities, while measures of PA intensity levels considerably varied depending on the rehabilitation progress. Single-day reliabilities of metrics of movement quantity decreased with rehabilitation progress, while metrics of movement quality increased. To achieve a mean reliability of 0.8, we found that three continuous recording days are required for out-patients, and 2 days for in-patients. Furthermore, the results show similar weekday and weekend wheeling activity for in- and out-patients. To our knowledge, this is the first study to investigate the reliability of an extended set of sensor-based measures of PA in both acute and chronic wheelchair-dependent SCI patients. The results provide recommendations for sensor-based assessments of PA in clinical SCI studies.