Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human-derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation-related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.

Testing Dynamic Balance in People with Multiple Sclerosis: A Correlational Study between Standard Posturography and Robotic-Assistive Device.

BACKGROUND: Robotic devices are known to provide pivotal parameters to assess motor functions in Multiple Sclerosis (MS) as dynamic balance. However, there is still a lack of validation studies comparing innovative technologies with standard solutions. Thus, this study's aim was to compare the postural assessment of fifty people with MS (PwMS) during dynamic tasks performed with the gold standard EquiTest® and the robotic platform hunova®, using Center of Pressure (COP)-related parameters and global balance indexes. METHODS: Pearson's ρ correlations were run for each COP-related measure and the global balance index was computed from EquiTest® and hunova® in both open (EO) and closed-eyes (EC) conditions. RESULTS: Considering COP-related parameters, all correlations were significant in both EO (0.337 ≤ ρ ≤ 0.653) and EC (0.344 ≤ ρ ≤ 0.668). Furthermore, Pearson's analysis of global balance indexes revealed relatively strong for visual and vestibular, and strong for somatosensory system associations (ρ = 0.573; ρ = 0.494; ρ = 0.710, respectively). CONCLUSIONS: Findings confirm the use of hunova® as a valid device for dynamic balance assessment in MS, suggesting that such a robotic platform could allow for a more sensitive assessment of balance over time, and thus a better evaluation of the effectiveness of personalized treatment, thereby improving evidence-based clinical practice.

Relationship between Timed Up and Go performance and quantitative biomechanical measures of balance.

Traumatic brain injury (TBI) impairs sensory-motor functions, with debilitating consequences on postural control and balance, which persist during the chronic stages of recovery. The Timed Up and Go (TUG) test is a reliable, safe, time-efficient, and one of the most widely used clinical measures to assess gait, balance, and fall risk in TBI patients and is extensively used in inpatient and outpatient settings. Although the TUG test has been used extensively due to its ease of performance and excellent reliability, limited research has been published that investigates the relationship between TUG performance and quantitative biomechanical measures of balance. The objective of this paper was to quantify the relationship between biomechanical variables of balance and the TUG scores in individuals with chronic TBI. Regression models were constructed using six biomechanical variables to predict TUG scores. The model that conservatively removed gait speed (i.e., TUG-1/GS) gave the best results, achieving a root-mean-square error of ∼±2 s and explaining over 69% of the variability.

Clinical, Kinematic and Muscle Assessment of Bilateral Coordinated Upper-Limb Movements Following Cervical Spinal Cord Injury.

Cervical spinal cord injury (cSCI) often results in bilateral impairment of the arms, leading to difficulties in performing daily activities. However, little is known about the neuromotor alterations that affect the ability of individuals with cSCI to perform coordinated movements with both arms. To address this issue, we developed and tested a functional assessment that integrates clinical, kinematic, and muscle activity measures, including the evaluation of bilateral arm movements. Twelve subjects with a C5-C7 spinal lesion and six unimpaired subjects underwent an evaluation that included three tests: the Manual Muscle Test, Range Of Motion test and Arm stabilisation test, a subsection of the "Van Lieshout arm/hand function test". During the latter, we recorded kinematic and muscle activity data from the upper-body during the execution of a set of movements that required participants to stabilize both arms against gravity at different configurations. Analytical methods, including muscle synergies, spinal maps, and Principal Component Analysis, were used to analyse the data. Clinical tests detected limitations in shoulder abduction-flexion of cSCI participants and alterations in elbows-wrists motor function. The instrumented assessment provided insight into how these limitations impacted the ability of cSCI participants to perform bilateral movements. They exhibited severe difficulty in performing movements involving over-the-shoulder motion and shoulder internal rotation due to altered patterns of activity of the scapular stabilizer muscles, latissimus dorsi, pectoralis, and triceps. Our findings shed light on the bilateral neuromotor changes that occur post-cSCI addressing not only motor deficits, but also the underlying abnormal, weak, or silent muscle activations.

Standard versus innovative robotic balance assessment for people with multiple sclerosis: a correlational study.

INTRODUCTION: Balance disorders are common in people with Multiple Sclerosis (PwMS) and, together with other impairments and disabilities, often prevent PwMS from performing their daily living activities. Besides clinical scales and performance tests, robotic platforms can provide more sensitive, specific, and objective monitoring. Validated technologies have been adopted as gold standard, but innovative robotic solutions would represent an opportunity to detect balance impairment in PwMS. AIM: Study's aim was to compare postural assessment of 46 PwMS with a relapsing-remitting form during static tasks performed with the novel robotic platform hunova® and the gold standard EquiTest®, METHODS: Pearson's r was run on Center of Pressure (COP)-related parameters and global static balance measures computed from hunova® and EquiTest® in eyes-open (EO) and eyes-closed (EC) conditions. In addition, agreeableness level toward the use of both devices was tested through numeric rating scale. RESULTS: Considering COP-related parameters, correlations were significant for all measures (p < .001). Interestingly, in EO, a strong correlation was shown for sway area (r = .770), while Medio-Lateral (ML) and Anterior-Posterior (AP) oscillation range, path length, ML and AP speed, ML and AP root mean square distance had a relatively strong association (.454 ≤ r ≤ .576). In EC, except for ML oscillation range showing a relatively strong correlation (r = .532), other parameters were strongly associated (.603 ≤ r ≤ .782). Correlations between global balance indexes of hunova® and EquiTest® revealed a relatively strong association between the Somatosensory Score in EquiTest® and the Somatosensory Index in hunova® (r = - .488). While in EO Static Balance Index from hunova® was highly correlated with Equilibrium score of EquiTest® (r = .416), Static Balance Index had a relatively strong association with both the Equilibrium (r = .482) and Strategy Score (r = .583) of EquiTest® in EC. Results from agreeableness rating scale revealed that hunova® was highly appreciated compared to EquiTest® (p = .044). CONCLUSIONS: hunova® represents an innovative adjunct to standard robotic balance evaluation for PwMS. This confirms that combining traditional and robotic assessments can more accurately detect balance impairments in MS.

Evaluation of a novel technology-supported fall prevention intervention - study protocol of a multi-centre randomised controlled trial in older adults at increased risk of falls.

BACKGROUND: Increasing number of falls and fall-related injuries in an aging society give rise to the need for effective fall prevention and rehabilitation strategies. Besides traditional exercise approaches, new technologies show promising options for fall prevention in older adults. As a new technology-based approach, the hunova robot can support fall prevention in older adults. The objective of this study is to implement and evaluate a novel technology-supported fall prevention intervention using the hunova robot compared to an inactive control group. The presented protocol aims at introducing a two-armed, multi-centre (four sites) randomised controlled trial, evaluating the effects of this new approach on the number of falls and number of fallers as primary outcomes. METHODS: The full clinical trial incorporates community-dwelling older adults at risk of falls with a minimum age of 65 years. Including a one-year follow-up measurement, all participants are tested four times. The training programme for the intervention group comprises 24-32 weeks in which training sessions are scheduled mostly twice a week; the first 24 training sessions use the hunova robot, these are followed by a home-based programme of 24 training sessions. Fall-related risk factors as secondary endpoints are measured using the hunova robot. For this purpose, the hunova robot measures the participants' performance in several dimensions. The test outcomes are input for the calculation of an overall score which indicates the fall risk. The hunova-based measurements are accompanied by the timed-up-and-go test as a standard test within fall prevention studies. DISCUSSION: This study is expected to lead to new insights which may help establish a new approach to fall prevention training for older adults at risk of falls. First positive results on risk factors can be expected after the first 24 training sessions using the hunova robot. As primary outcomes, the number of falls and fallers within the study (including the one-year follow-up period) are the most relevant parameters that should be positively influenced by our new approach to fall prevention. After the study completion, approaches to examine the cost-effectiveness and develop an implementation plan are relevant aspects for further steps. TRIAL REGISTRATION: German Clinical Trial Register (DRKS), ID: DRKS00025897. Prospectively registered 16 August 2021, https://drks.de/search/de/trial/DRKS00025897 .

A Lifespan Approach to Balance in Static and Dynamic Conditions: The Effect of Age on Balance Abilities.

Postural control is a complex sensorimotor skill that is fundamental to our daily life. The abilities to maintain and recover balance degrade with age. However, the time decay of balance performance with age is not well understood. In this study, we aim at quantifying the age-dependent changes in standing balance under static and dynamic conditions. We tested 272 healthy subjects with ages ranging from 20 to 90. Subjects maintained the upright posture while standing on the robotic platform hunova®. In the evaluation of static balance, subjects stood on the fixed platform both with eyes open (EO) and eyes closed (EC). In the dynamic condition, subjects stood with eyes open on the moving foot platform that provided three different perturbations: (i) an inclination proportional to the center of pressure displacements, (ii) a pre-defined predictable motion, and (iii) an unpredictable and unexpected tilt. During all these tests, hunova® measured the inclination of the platform and the displacement of the center of pressure, while the trunk movements were recorded with an accelerometer placed on the sternum. To quantify balance performance, we computed spatio-temporal parameters typically used in clinical environments from the acceleration measures: mean velocity, variability of trunk motion, and trunk sway area. All subjects successfully completed all the proposed exercises. Their motor performance in the dynamic balance tasks quadratically changed with age. Also, we found that the reliance on visual feedback is not age-dependent in static conditions. All subjects well-tolerated the proposed protocol independently of their age without experiencing fatigue as we chose the timing of the evaluations based on clinical needs and routines. Thus, this study is a starting point for the definition of robot-based assessment protocols aiming at detecting the onset of age-related standing balance deficits and allowing the planning of tailored rehabilitation protocols to prevent falls in older adults.

Recovery of Distal Arm Movements in Spinal Cord Injured Patients with a Body-Machine Interface: A Proof-of-Concept Study.

BACKGROUND: The recovery of upper limb mobility and functions is essential for people with cervical spinal cord injuries (cSCI) to maximize independence in daily activities and ensure a successful return to normality. The rehabilitative path should include a thorough neuromotor evaluation and personalized treatments aimed at recovering motor functions. Body-machine interfaces (BoMI) have been proven to be capable of harnessing residual joint motions to control objects like computer cursors and virtual or physical wheelchairs and to promote motor recovery. However, their therapeutic application has still been limited to shoulder movements. Here, we expanded the use of BoMI to promote the whole arm's mobility, with a special focus on elbow movements. We also developed an instrumented evaluation test and a set of kinematic indicators for assessing residual abilities and recovery. METHODS: Five inpatient cSCI subjects (four acute, one chronic) participated in a BoMI treatment complementary to their standard rehabilitative routine. The subjects wore a BoMI with sensors placed on both proximal and distal arm districts and practiced for 5 weeks. The BoMI was programmed to promote symmetry between right and left arms use and the forearms' mobility while playing games. To evaluate the effectiveness of the treatment, the subjects' kinematics were recorded while performing an evaluation test that involved functional bilateral arms movements, before, at the end, and three months after training. RESULTS: At the end of the training, all subjects learned to efficiently use the interface despite being compelled by it to engage their most impaired movements. The subjects completed the training with bilateral symmetry in body recruitment, already present at the end of the familiarization, and they increased the forearm activity. The instrumental evaluation confirmed this. The elbow motion's angular amplitude improved for all subjects, and other kinematic parameters showed a trend towards the normality range. CONCLUSION: The outcomes are preliminary evidence supporting the efficacy of the proposed BoMI as a rehabilitation tool to be considered for clinical practice. It also suggests an instrumental evaluation protocol and a set of indicators to assess and evaluate motor impairment and recovery in cSCI.

The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study.

BACKGROUND: Nitroglycerin is used for acute reduction in uterine tone. Prolonged oxytocin exposure causes desensitization of oxytocin receptors. It is unknown if nitroglycerin exposure impacts the subsequent action of oxytocin in the setting of oxytocin receptor desensitization. This study investigated the effects of nitroglycerin on oxytocin-desensitized and oxytocin-naïve human myometrium and the subsequent response to oxytocin dose-response testing in vitro. METHODS: Myometrial samples from 17 elective cesarean deliveries were divided into strips and allocated to 1 of 4 groups: (1) oxytocin desensitized and no nitroglycerin; (2) oxytocin desensitized and nitroglycerin; (3) oxytocin naïve and nitroglycerin; and (4) oxytocin naïve and no nitroglycerin. Final analysis included 28 strips per group. Nitroglycerin groups were exposed to incremental concentrations of nitroglycerin, while no nitroglycerin groups were kept in control (physiological salt) solution. All groups then underwent oxytocin dose-response testing. Primary outcome was motility index (amplitude × frequency; grams × contractions per 10 minutes [g·c/10 min]). Secondary outcomes were amplitude (g), frequency (contractions/10 minutes), and area under the curve (g·s). All outcomes (nitroglycerin and oxytocin dose-response periods) were expressed as a percentage change from baseline. Values were log transformed, compared using regression modeling and reported as the ratio of 2 geometric means (relative difference). RESULTS: No significant difference was observed in motility index following nitroglycerin administration in oxytocin-desensitized versus oxytocin-naïve groups (relative difference = 19.0%; 95% confidence interval [CI], -32.6 to 109.9; P = .55). On oxytocin dose-response testing, motility index was highest in oxytocin-naïve and no nitroglycerin samples (group 4) (1.356 g·c/10 minutes) followed by oxytocin-naïve and nitroglycerin (group 3) (0.882 g·c/10 minutes), oxytocin-desensitized and no nitroglycerin (group 1) (0.769 g·c/10 minutes), and oxytocin-desensitized and nitroglycerin (group 2) (0.651 g·c/10 minutes) samples. Motility index was significantly reduced in group 1 vs 4 (relative difference = -43.3%; 95% CI, -66.5 to -4.1; P = .034) and group 2 vs 4 (relative difference = -52.0%; 95% CI, -70.9 to -20.8; P = .004). While in groups 3 vs 4, both amplitude (relative difference = -17.8%; 95% CI, -30.9 to -2.2; P = .27) and area under the curve (AUC; relative difference = -17.5%; 95% CI, -30.7 to -1.8; P = .030) were reduced. CONCLUSIONS: Nitroglycerin-induced relaxation was not different between oxytocin-desensitized and oxytocin-naïve human myometrial strips in vitro. However, oxytocin-induced contractility was attenuated after nitroglycerin exposure in both oxytocin-desensitized and oxytocin-naïve samples, with maximum attenuation observed in desensitized tissues. This finding warrants further clinical studies to explore uterine responsiveness to oxytocin in women with oxytocin-augmented labors after nitroglycerin administration.

Modified Functional Reach Test: Upper-Body Kinematics and Muscular Activity in Chronic Stroke Survivors.

Effective control of trunk muscles is fundamental to perform most daily activities. Stroke affects this ability also when sitting, and the Modified Functional Reach Test is a simple clinical method to evaluate sitting balance. We characterize the upper body kinematics and muscular activity during this test. Fifteen chronic stroke survivors performed twice, in separate sessions, three repetitions of the test in forward and lateral directions with their ipsilesional arm. We focused our analysis on muscles of the trunk and of the contralesional, not moving, arm. The bilateral activations of latissimi dorsi, trapezii transversalis and oblique externus abdominis were left/right asymmetric, for both test directions, except for the obliquus externus abdominis in the frontal reaching. Stroke survivors had difficulty deactivating the contralesional muscles at the end of each trial, especially the trapezii trasversalis in the lateral direction. The contralesional, non-moving arm had muscular activations modulated according to the movement phases of the moving arm. Repeating the task led to better performance in terms of reaching distance, supported by an increased activation of the trunk muscles. The reaching distance correlated negatively with the time-up-and-go test score.

Dynamic Stability and Trunk Control Improvements Following Robotic Balance and Core Stability Training in Chronic Stroke Survivors: A Pilot Study.

Stroke survivors show greater postural oscillations and altered muscular activation compared to healthy controls. This results in difficulties in walking and standing, and in an increased risk of falls. A proper control of the trunk is related to a stable walk and to a lower falling risk; to this extent, rehabilitative protocols are currently working on core stability. The main objective of this work was to evaluate the effectiveness of trunk and balance training performed with a new robotic device designed for evaluation and training of balance and core stability, in improving the recovery of chronic stroke patients compared with a traditional physical therapy program. Thirty chronic stroke patients, randomly divided in two groups, either underwent a traditional rehabilitative protocol, or a robot-based program. Each patient was assessed before and after the rehabilitation and at 3-months follow-up with clinical and robot-based evaluation exercises focused on static and dynamic balance and trunk control. Results from clinical scores showed an improvement in both groups in balance and trunk control. Robot-based indices analysis indicated that the experimental group showed greater improvements in proprioceptive control, reactive balance and postural control in unstable conditions, compared to the control group, showing an improved trunk control with reduced compensatory strategies at the end of the training. Moreover, the experimental group had an increased retention of the benefits obtained with training at 3 months follow up. These results support the idea that such robotic device is a promising tool for stroke rehabilitation.

Development and validation of a robotic multifactorial fall-risk predictive model: A one-year prospective study in community-dwelling older adults.

BACKGROUND: Falls in the elderly are a major public health concern because of their high incidence, the involvement of many risk factors, the considerable post-fall morbidity and mortality, and the health-related and social costs. Given that many falls are preventable, the early identification of older adults at risk of falling is crucial in order to develop tailored interventions to prevent such falls. To date, however, the fall-risk assessment tools currently used in the elderly have not shown sufficiently high predictive validity to distinguish between subjects at high and low fall risk. Consequently, predicting the risk of falling remains an unsolved issue in geriatric medicine. This one-year prospective study aims to develop and validate, by means of a cross-validation method, a multifactorial fall-risk model based on clinical and robotic parameters in older adults. METHODS: Community-dwelling subjects aged ≥ 65 years were enrolled. At the baseline, all subjects were evaluated for history of falling and number of drugs taken daily, and their gait and balance were evaluated by means of the Timed "Up & Go" test (TUG), Gait Speed (GS), Short Physical Performance Battery (SPPB) and Performance-Oriented Mobility Assessment (POMA). They also underwent robotic assessment by means of the hunova robotic device to evaluate the various components of balance. All subjects were followed up for one-year and the number of falls was recorded. The models that best predicted falls-on the basis of: i) only clinical parameters; ii) only robotic parameters; iii) clinical plus robotic parameters-were identified by means of a cross-validation method. RESULTS: Of the 100 subjects initially enrolled, 96 (62 females, mean age 77.17±.49 years) completed the follow-up and were included. Within one year, 32 participants (33%) experienced at least one fall ("fallers"), while 64 (67%) did not ("non-fallers"). The best classifier model to emerge from cross-validated fall-risk estimation included eight clinical variables (age, sex, history of falling in the previous 12 months, TUG, Tinetti, SPPB, Low GS, number of drugs) and 20 robotic parameters, and displayed an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.72-0.90). Notably, the model that included only three of these clinical variables (age, history of falls and low GS) plus the robotic parameters showed similar accuracy (ROC AUC 0.80, 95% CI: 0.71-0.89). In comparison with the best classifier model that comprised only clinical parameters (ROC AUC: 0.67; 95% CI: 0.55-0.79), both models performed better in predicting fall risk, with an estimated Net Reclassification Improvement (NRI) of 0.30 and 0.31 (p = 0.02), respectively, and an estimated Integrated Discrimination Improvement (IDI) of 0.32 and 0.27 (p<0.001), respectively. The best model that comprised only robotic parameters (the 20 parameters identified in the final model) achieved a better performance than the clinical parameters alone, but worse than the combination of both clinical and robotic variables (ROC AUC: 0.73, 95% CI 0.63-0.83). CONCLUSION: A multifactorial fall-risk assessment that includes clinical and hunova robotic variables significantly improves the accuracy of predicting the risk of falling in community-dwelling older people. Our data suggest that combining clinical and robotic assessments can more accurately identify older people at high risk of falls, thereby enabling personalized fall-prevention interventions to be undertaken.

The effect of morbid obesity or advanced maternal age on oxytocin-induced myometrial contractions: an in vitro study.

PURPOSE: The purpose of this study was to investigate myometrial contractility induced by oxytocin in women with advanced maternal age (AMA) and morbid obesity (MO). We hypothesized that both oxytocin-pretreated and oxytocin-naïve myometrial tissues from women of AMA and women who are MO would exhibit poor myometrial contractility compared with women that are younger and of normal body mass index (BMI). METHODS: This prospective in vitro study was conducted using myometrial samples obtained from women undergoing elective Cesarean deliveries. Three groups of patient were studied: control (≤ 35 yr; BMI, 20-24.9 kg·m-2), AMA (≥ 40 yr; BMI, 20-24.9 kg·m-2), and MO (≤ 35 yr BMI, ≥ 40 kg·m-2). Each myometrial strip was either pretreated with oxytocin 10-5 M or left in physiologic salt solution for two hours. This was followed by a dose-response testing to oxytocin (10-10 M to 10-5 M), during which contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. RESULTS: The MI of contractions was reduced in oxytocin-pretreated samples when compared with their oxytocin naïve counterparts in control (estimated difference -69%; 95% confidence interval [CI], -82 to -48; P < 0.001) and AMA groups (estimated difference, -44%; 95% CI, -68 to -2; P = 0.07). The MI of contractions was not different between oxytocin naïve and oxytocin-pretreated samples from MO women (estimated difference, -26%; 95% CI, -63 to 49; P = 0.46); however, it was significantly lower in these groups compared with oxytocin-naïve samples from the control group. CONCLUSIONS: Oxytocin pre-treatment reduced myometrial contractility in AMA and control group women compared with their oxytocin-naïve counterparts, as a function of the desensitization phenomenon. Attenuated oxytocin-induced myometrial contractility in MO women in both oxytocin-pretreated and oxytocin-naïve samples suggests that these women have intrinsically reduced uterine contractile ability. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01865669; registered 28 May, 2013).

RéSUMé: OBJECTIF: L'objectif de cette recherche était d'étudier la contractilité myométriale induite par l'oxytocine chez des femmes d'âge maternel avancé (AMA) et ayant une obésité morbide (OM). Nous avons formulé l'hypothèse que les tissus de myomètre prétraités avec de l'oxytocine ainsi que les tissus naïfs d'oxytocine provenant de femmes d'AMA ou ayant une OM présenteraient une mauvaise contractilité comparativement à des femmes plus jeunes et à l'indice de masse corporelle (IMC) normal. MéTHODES: Cette étude prospective in vitro a été menée en utilisant des échantillons de myomètre prélevés sur des femmes accouchant par césarienne planifiée. Trois groupes de patientes ont été étudiés : contrôles (≤ 35 ans; IMC, 20 à 24,9 kg·m−2), AMA (≥ 40 ans; IMC, 20 à 24,9 kg·m−2) et OM (≤ 35 ans IMC, ≥ 40 kg·m−2). Chaque bandelette de myomètre a été prétraitée avec de l'oxytocine 10−5 M ou laissée dans une solution salée physiologique pendant deux heures. Cela a été suivi de tests de réponse à des doses croissantes d'oxytocine (10−10 M à 10−5 M) au cours desquels les paramètres contractiles ont été mesurés. Le critère d'évaluation principal était l'indice de motilité (IM, amplitude × fréquence) des contractions. RéSULTATS: Cet IM des contractions était diminué dans les échantillons prétraités avec l'oxytocine, comparativement à leurs équivalents naïfs d'oxytocine dans les groupes contrôles (différence estimée -69 %; intervalle de confiance [IC] à 95 % : -82 à -48; P < 0,001) et AMA (différence estimée, -44 %; IC à 95 %, -68 à -2; P = 0,07). L'IM des contractions n'était pas différent entre les échantillons naïfs d'oxytocine et les échantillons prétraités provenant de femmes ayant une OM (différence estimée, -26 %; IC à 95 %, -63 à 49; P = 0,46). Il était cependant significativement plus faible dans ces groupes comparativement aux échantillons naïfs pour l'oxytocine provenant du groupe contrôle. CONCLUSIONS: Le prétraitement à l'oxytocine a réduit la contractilité myométriale des femmes des groupes AMA et contrôle comparativement à celle des prélèvements naïfs d'oxytocine en fonction d'un phénomène de désensibilisation. L'atténuation de la contractilité myométriale induite par l'oxytocine dans les échantillons prétraités et naïfs d'oxytocine chez les femmes présentant une OM suggère que ces dernières présentent une capacité contractile intrinsèquement réduite de l'utérus. ENREGISTREMENT DE L'ESSAI CLINIQUE: www.clinicaltrials.gov (NCT01865669; enregistré le 28 mai 2013).

Haptic vs sensorimotor training in the treatment of upper limb dysfunction in multiple sclerosis: A multi-center, randomised controlled trial.

BACKGROUND: In multiple sclerosis (MS) exercise improves upper limb functions, but it is unclear what training types are more effective. OBJECTIVE: This study compares robot-assisted training based on haptic or sensorimotor exercise. METHODS: 41clinically definite MS subjects with upper limb impairment were randomised into two groups: (i) Haptic and (ii) Sensorimotor. Subjects in the Haptic performed a robot-assisted training protocol designed to counteract incoordination and weakness. The task -interaction with a virtual mass-spring system against a resistive load- requires coordination skills. Task difficulty and magnitude of resistive load were automatically adjusted to the individual impairment. Subjects in the Sensorimotor performed reaching movements under visual control; the robot generated no forces. Both groups underwent eight training sessions (40 min/session, 2 sessions/week). Treatment outcome were 9HPT and ARAT scores. RESULTS: The average 9HPT score decreased from 74±9 s to 61±8 s for the Haptic and from 49±6 s to 44±6 s. We found a significant Treatment (p=.0453) and Time differences (p=.005), but no significant Treatment×Time interactions although we found that the absolute change was only significant in the Haptic group (p=.011). We observed no significant changes in the ARAT score. Participants tolerated treatments well with a low drop-out rate. In the subjects evaluated at after 12 week (11 subject in sensory-motor and 17 in haptic group) no retention of the effect was found. CONCLUSIONS: Task oriented training may improve upper limb function in persons with MS especially in prevalent pyramidal impaired subjects without maintain the effects after three months. CLINICAL TRIAL REGISTRATION NUMBER: NCT02711566 (clinicaltrial.gov).

Robotic balance assessment in community-dwelling older people with different grades of impairment of physical performance.

BACKGROUND: Impaired physical performance is common in older adults and has been identified as a major risk factor for falls. To date, there are no conclusive data on the impairment of balance parameters in older subjects with different levels of physical performance. AIMS: The aim of this study was to investigate the relationship between different grades of physical performance, as assessed by the Short Physical Performance Battery (SPPB), and the multidimensional balance control parameters, as measured by means of a robotic system, in community-dwelling older adults. METHODS: This study enrolled subjects aged ≥ 65 years. Balance parameters were assessed by the hunova robot in static and dynamic (unstable and perturbating) conditions, in both standing and seated positions and with the eyes open/closed. RESULTS: The study population consisted of 96 subjects (62 females, mean age 77.2 ± 6.5 years). According to their SPPB scores, subjects were separated into poor performers (SPPB < 8, n = 29), intermediate performers (SPPB = 8-9, n = 29) and good performers (SPPB > 9, n = 38). Poor performers displayed significantly worse balance control, showing impaired trunk control in most of the standing and sitting balance tests, especially in dynamic (both with unstable and perturbating platform/seat) conditions. CONCLUSIONS: For the first time, multidimensional balance parameters, as detected by the hunova robotic system, were significantly correlated with SPPB functional performances in community-dwelling older subjects. In addition, balance parameters in dynamic conditions proved to be more sensitive in detecting balance impairments than static tests.

Design and Development of a Novel Core, Balance and Lower Limb Rehabilitation Robot: hunova®.

This article describes the motivation behind and the technical aspects at the basis of the development of the innovative rehabilitation robot hunova®. The paper describes in detail the hardware and software design of the system and summarizes the clinical studies carried out to validate the technology.

Robot-based assessment of sitting and standing balance: preliminary results in Parkinson's disease.

Postural responses to unstable conditions or perturbations are important predictors of the risk of falling and can reveal balance deficits in people with neurological disorders, such as Parkinson's Disease (PD). However, there is a lack of evidences related to devices and protocols providing a comprehensive and quantitative evaluation of postural responses in different stability conditions. We tested ten people with PD and ten controls on a robotic platform capable to provide different mechanical interactions and to measure the center of pressure displacement, while trunk acceleration was recorded with a sensor placed on the sternum. We evaluated performance while maintaining upright posture in unperturbed, perturbed, and unstable conditions. The latter was tested while standing and sitting. We measured whether the proposed exercises and metrics could highlight differences in postural control. Participants with PD had worse performance metrics when standing under unperturbed or unstable conditions, and when sitting on the unstable platform. PD subjects in response to a forward perturbation showed bigger trunk oscillations coupled with a sharper increase of the CoP backward displacement. These responses could be due to higher stiffness of lower limb which leads to postural instability. The exercises and the proposed metrics highlighted differences in postural control, hence they can be used in clinical environment for the assessment and progression of postural impairments.

The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-Induced Contractility of Human Myometrium In Vitro.

BACKGROUND: Prolonged continuous oxytocin administration during labor may induce oxytocin receptor desensitization, which attenuates the response of the myometrium to further oxytocin, increasing the risk of postpartum hemorrhage. The literature comparing pulsatile (intermittent) versus continuous oxytocin administration for induction and augmentation of labor is inconsistent with regard to maternal outcomes. We aimed to determine the effect of intermittent versus continuous oxytocin preexposure on myometrial responsiveness to subsequent oxytocin. We hypothesized that intermittent oxytocin pretreatment would result in superior subsequent oxytocin-induced contractility than continuous oxytocin pretreatment. METHODS: This in vitro study was undertaken using myometrium obtained from women undergoing elective cesarean deliveries. Each myometrial strip was mounted in an individual organ bath with physiological salt solution under homeostatic conditions and allocated to one of 3 groups: (1) control (no pretreatment); (2) continuous (pretreatment with oxytocin 10(-5) M for 2 hours); or (3) intermittent (pretreatment with alternating oxytocin 10 M and physiological salt solution every 15 minutes, for 2 hours). After pretreatment, dose-response testing to oxytocin 10(-5) to 10(-5) M was performed and contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. RESULTS: Eighteen women were recruited, and 86 successful experiments were performed (control n = 29, continuous n = 28, intermittent n = 29). The means (standard errors) of MI (√g·contractions/10 min) in the control, continuous, and intermittent groups were 2.34 (0.09), 1.78 (0.09), and 2.13 (0.11), respectively. The MI was significantly reduced in the continuous group when compared to the control (estimated difference [95% confidence interval {CI}], -0.56 [-0.81 to -0.31]; P < .01) and intermittent group (estimated difference [95% CI], -0.35 [-0.62 to -0.08]; P = .01). There was no significant difference in MI between the intermittent and control group (estimated difference [95% CI], -0.21 [-0.51 to 0.09]; P = .17). CONCLUSIONS: Human myometrium remains more responsive to subsequent oxytocin after intermittent compared to continuous exposure to oxytocin, most likely due to reduction in oxytocin receptor desensitization, or facilitation of receptor resensitization in the intermittent group. Hence, intermittent oxytocin administration during labor warrants further investigation as a technique to preserve uterine oxytocin responsiveness.

Recovery and compensation after robotic assisted gait training in chronic stroke survivors.

Background: Gait re-education is a primary rehabilitation goal after stroke. In the last decades, robots with different mechanical structures have been extensively used in the clinical practice for gait training of stroke survivors. However, the effectiveness of robotic training is still controversial, especially for chronic subjects. In this study, we investigated the short-term effects of gait training assisted by an endpoint robot in a population of chronic stroke survivors.Methods: Subjects were evaluated before and after training with clinical scales and instrumented gait analysis. Our primary outcome indicator was the walking speed. Next, we investigated the changes in kinetic and kinematic gait patterns as well as the intersegmental coordination at the level of the lower limbs.Results: Most subjects improved their speed in over-ground walking, by modifying the temporal more than the spatial gait parameters. These changes led to an improvement in the ankle power for both sides and to a slight reduction of the inclination of the pelvis during the swing phase, mainly due to a decreased knee flexion and an increased hip extension on the unimpaired leg.Conclusions: These results indicate that the proposed training induced mainly a functional change rather than an improvement of the quality of gait.Implication for RehabilitationGait re-education is a primary goal in stroke rehabilitation.Nowadays several robotic devices for gait rehabilitation are used in the clinical practice, but their effectiveness is controversial, especially for chronic survivors.After a 20-session training with an endpoint robot the chronic stroke survivors showed an improvement in overground gait speed.The increased gait speed was mainly due to functional changes of the temporal parameters and of the kinetic variables at the level of both ankle joints, as well as to a reduction of compensatory strategies observable in the unimpaired side.

Effect of magnesium sulfate on oxytocin-induced contractility in human myometrium: an in vitro study.

PURPOSE: The purpose of this study was to determine the contractile patterns induced by oxytocin in myometrium exposed to magnesium sulfate (MgSO4). We hypothesized that MgSO4 pretreatment would reduce oxytocin-induced myometrial contractions in both oxytocin-naïve and oxytocin-desensitized myometrium. METHODS: In this prospective in vitro study, myometrial samples were obtained from 26 women undergoing elective Cesarean deliveries. Samples were divided into six groups. Four groups were apportioned to no pretreatment (control group), oxytocin 10-5 M pretreatment (desensitization group), MgSO4 3.5 mM pretreatment, and MgSO4 3.5 mM + oxytocin 10-5M pretreatment. This was followed by dose-response testing to oxytocin 10-10 to 10-5M in all four groups. Two additional groups included MgSO4 3.5 mM pretreatment and MgSO4 3.5 mM + oxytocin 10-5 M pretreatment, followed by dose-response testing to oxytocin along with MgSO4 3.5 mM. The outcomes were motility index (MI), as defined by the amplitude (g) × frequency of myometrial contractions (c) over ten minutes, and area under the curve (AUC). RESULTS: In oxytocin-naïve myometrium, the mean (standard error [SE]) MI was not affected by MgSO4 pretreatment [3.31 (0.20) √g⋅c/10 min] as compared with control (P = 0.88), even when MgSO4 was continued during dose-response testing [2.50 (0.19) √g⋅c/10 min; P = 0.41]. In the oxytocin-desensitized model, mean (SE) MI was not affected by MgSO4 pretreatment [2.60 (0.21) √g⋅c/10 min; P = 0.68], but when MgSO4 was continued during the dose-response period, the MI was significantly reduced compared with control [1.89 (0.13) √g⋅c/10 min; P < 0.001]. The results for AUC were similar to MI, except for a significant reduction in oxytocin-naïve myometrium when MgSO4 was continued during dose-response testing (P = 0.02). CONCLUSION: Magnesium sulfate pretreatment does not impair oxytocin-induced myometrial contractility in oxytocin-naïve or desensitized myometrium unless it is continued during oxytocin dose-response testing. These results suggest that its tocolytic effect is likely dependent on an extracellular mechanism. The study was registered with ClinicalTrials.gov, number NCT02647268.