Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques.

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Postpyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage fluid. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage fluid following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that postpyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. IMPORTANCE SARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution, and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however, no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here, we report that oral administration of live SARS-CoV-2 in nonhuman primates may offer prophylactic benefits, but the formulation and route of administration will require further optimization.

Feasibility of a Wireless Implantable Multi-electrode System for High-bandwidth Prosthetic Interfacing: Animal and Cadaver Study.

BACKGROUND: Currently used prosthetic solutions in upper extremity amputation have limited functionality, owing to low information transfer rates of neuromuscular interfacing. Although surgical innovations have expanded the functional potential of the residual limb, available interfaces are inefficacious in translating this potential into improved prosthetic control. There is currently no implantable solution for functional interfacing in extremity amputation which offers long-term stability, high information transfer rates, and is applicable for all levels of limb loss. In this study, we presented a novel neuromuscular implant, the the Myoelectric Implantable Recording Array (MIRA). To our knowledge, it is the first fully implantable system for prosthetic interfacing with a large channel count, comprising 32 intramuscular electrodes. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the MIRA in terms of biocompatibility, functionality, and feasibility of implantation to lay the foundations for clinical application. This was achieved through small- and large-animal studies as well as test surgeries in a human cadaver. METHODS: We evaluated the biocompatibility of the system's intramuscular electromyography (EMG) leads in a rabbit model. Ten leads as well as 10 pieces of a biologically inert control material were implanted into the paravertebral muscles of four animals. After a 3-month implantation, tissue samples were taken and histopathological assessment performed. The probes were scored according to a protocol for the assessment of the foreign body response, with primary endpoints being inflammation score, tissue response score, and capsule thickness in µm. In a second study, chronic functionality of the full system was evaluated in large animals. The MIRA was implanted into the shoulder region of six dogs and three sheep, with intramuscular leads distributed across agonist and antagonist muscles of shoulder flexion. During the observation period, regular EMG measurements were performed. The implants were removed after 5 to 6 months except for one animal, which retained the implant for prolonged observation. Primary endpoints of the large-animal study were mechanical stability, telemetric capability, and EMG signal quality. A final study involved the development of test surgeries in a fresh human cadaver, with the goal to determine feasibility to implant relevant target muscles for prosthetic control at all levels of major upper limb amputation. RESULTS: Evaluation of the foreign body reaction revealed favorable biocompatibility and a low-grade tissue response in the rabbit study. No differences regarding inflammation score (EMG 4.60 ± 0.97 [95% CI 4.00 to 5.20] versus control 4.20 ± 1.48 [95% CI 3.29 to 5.11]; p = 0.51), tissue response score (EMG 4.00 ± 0.82 [95% CI 3.49 to 4.51] versus control 4.00 ± 0.94 [95% CI 3.42 to 4.58]; p > 0.99), or thickness of capsule (EMG 19.00 ± 8.76 µm [95% CI 13.57 to 24.43] versus control 29.00 ± 23.31 µm [95% CI 14.55 to 43.45]; p = 0.29) were found compared with the inert control article (high-density polyethylene) after 3 months of intramuscular implantation. Throughout long-term implantation of the MIRA in large animals, telemetric communication remained unrestricted in all specimens. Further, the implants retained the ability to record and transmit intramuscular EMG data in all animals except for two sheep where the implants became dislocated shortly after implantation. Electrode impedances remained stable and below 5 kΩ. Regarding EMG signal quality, there was little crosstalk between muscles and overall average signal-to-noise ratio was 22.2 ± 6.2 dB. During the test surgeries, we found that it was possible to implant the MIRA at all major amputation levels of the upper limb in a human cadaver (the transradial, transhumeral, and glenohumeral levels). For each level, it was possible to place the central unit in a biomechanically stable environment to provide unhindered telemetry, while reaching the relevant target muscles for prosthetic control. At only the glenohumeral level, it was not possible to reach the teres major and latissimus dorsi muscles, which would require longer lead lengths. CONCLUSION: As assessed in a combination of animal model and cadaver research, the MIRA shows promise for clinical research in patients with limb amputation, where it may be employed for all levels of major upper limb amputation to provide long-term stable intramuscular EMG transmission. CLINICAL RELEVANCE: In our study, the MIRA provided high-bandwidth prosthetic interfacing through intramuscular electrode sites. Its high number of individual EMG channels may be combined with signal decoding algorithms for accessing spinal motor neuron activity after targeted muscle reinnervation, thus providing numerous degrees of freedom. Together with recent innovations in amputation surgery, the MIRA might enable improved control approaches for upper limb amputees, particularly for patients with above-elbow amputation where the mismatch between available control signals and necessary degrees of freedom for prosthetic control is highest.

Rehabilitation of high upper limb amputees after Targeted Muscle Reinnervation.

STUDY DESIGN: This is a Delphi study based on a scoping literature review. INTRODUCTION: Targeted muscle reinnervation (TMR) enables patients with high upper limb amputations to intuitively control a prosthetic arm with up to six independent control signals. Although there is a broad agreement regarding the importance of structured motor learning and prosthetic training after such nerve transfers, to date, no evidence-based protocol for rehabilitation after TMR exists. PURPOSE OF THE STUDY: We aimed at developing a structured rehabilitation protocol after TMR surgery after major upper limb amputation. The purpose of the protocol is to guide clinicians through the full rehabilitation process, from presurgical patient education to functional prosthetic training. METHODS: European clinicians and researchers working in upper limb prosthetic rehabilitation were invited to contribute to a web-based Delphi study. Within the first round, clinical experts were presented a summary of recent literature and were asked to describe the rehabilitation steps based on their own experience and scientific evidence. The second round was used to refine these steps, while the importance of each step was rated within the third round. RESULTS: Experts agreed on a rehabilitation protocol that consists of 16 steps and starts before surgery. It is based on two overarching principles, namely the necessity of multiprofessional teamwork and a careful selection and education of patients within the rehabilitation team. Among the different steps in therapy, experts rated the training with electromyographic biofeedback as the most important one. DISCUSSION: Within this study, a first rehabilitation protocol for TMR patients based on a broad experts' consensus and relevant literature could be developed. The detailed steps for rehabilitation start well before surgery and prosthetic fitting, and include relatively novel interventions as motor imagery and biofeedback. Future studies need to further investigate the clinical outcomes and thereby improve therapists' practice. CONCLUSION: Graded rehabilitation offered by a multiprofessional team is needed to enable individuals with upper limb amputations and TMR to fully benefit from prosthetic reconstruction. LEVEL OF EVIDENCE: Low.

Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease.

BACKGROUND: Ebola virus disease (EVD) supportive care strategies are largely guided by retrospective observational research. This study investigated the effect of EVD supportive care algorithms on duration of survival in a controlled nonhuman primate (NHP) model. METHODS: Fourteen rhesus macaques were challenged intramuscularly with a target dose of Ebola virus (1000 plaque-forming units; Kikwit). NHPs were allocated to intensive care unit (ICU)-like algorithms (n = 7), intravenous fluids plus levofloxacin (n = 2), or a control group (n = 5). The primary outcome measure was duration of survival, and secondary outcomes included changes in clinical laboratory values. RESULTS: Duration of survival was not significantly different between the pooled ICU-like algorithm and control groups (8.2 vs 6.9 days of survival; hazard ratio; 0.50; P = .25). Norepinephrine was effective in transiently maintaining baseline blood pressure. NHPs treated with ICU-like algorithms had delayed onset of liver and kidney injury. CONCLUSIONS: While an obvious survival difference was not observed with ICU-like care, clinical observations from this model may aid in EVD supportive care NHP model refinement.

Validity, Reliability and Sensitivity to Change of Three Consumer-Grade Activity Trackers in Controlled and Free-Living Conditions among Older Adults.

Wrist-worn consumer-grade activity trackers are popular devices, developed mainly for personal use. This study aimed to explore the validity, reliability and sensitivity to change of movement behaviors metrics from three activity trackers (Polar Vantage M, Garmin Vivoactive 4s and Garmin Vivosport) in controlled and free-living conditions when worn by older adults. Participants (n = 28; 74 ± 5 years) underwent a videotaped laboratory protocol while wearing all three trackers. On a separate occasion, participants (n = 17 for each of the trackers) wore one (randomly assigned) tracker and a research-grade activity monitor ActiGraph wGT3X-BT simultaneously for six consecutive days. Both Garmin trackers showed excellent performance for step counts, with a mean absolute percentage error (MAPE) below 20% and intraclass correlation coefficient (ICC2,1) above 0.90 (p < 0.05). The MAPE for sleep time was within 10% for all the trackers tested, while it was far beyond 20% for all other movement behaviors metrics. The results suggested that all three trackers could be used for measuring sleep time with a high level of accuracy, and both Garmin trackers could also be used for step counts. All other output metrics should be used with caution. The results provided in this study could be used to guide choice on activity trackers aiming for different purposes-individual use, longitudinal monitoring or in clinical trial setting.

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly.

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared-the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

Skeletal Muscle Gene Expression in Long-Term Endurance and Resistance Trained Elderly.

Physical exercise is deemed the most efficient way of counteracting the age-related decline of skeletal muscle. Here we report a transcriptional study by next-generation sequencing of vastus lateralis biopsies from elderly with a life-long high-level training practice (n = 9) and from age-matched sedentary subjects (n = 5). Unsupervised mixture distribution analysis was able to correctly categorize trained and untrained subjects, whereas it failed to discriminate between individuals who underwent a prevalent endurance (n = 5) or a prevalent resistance (n = 4) training, thus showing that the training mode was not relevant for sarcopenia prevention. KEGG analysis of transcripts showed that physical exercise affected a high number of metabolic and signaling pathways, in particular those related to energy handling and mitochondrial biogenesis, where AMPK and AKT-mTOR signaling pathways are both active and balance each other, concurring to the establishment of an insulin-sensitive phenotype and to the maintenance of a functional muscle mass. Other pathways affected by exercise training increased the efficiency of the proteostatic mechanisms, consolidated the cytoskeletal organization, lowered the inflammation level, and contrasted cellular senescence. This study on extraordinary individuals who trained at high level for at least thirty years suggests that aging processes and exercise training travel the same paths in the opposite direction.

Bionic hand as artificial organ: Current status and future perspectives.

Even though the hand comprises only 1% of our body weight, about 30% of our central nervous systems (CNS) capacity is related to its control. The loss of a hand thus presents not only the loss of the most important tool allowing us to interact with our environment, but also leaves a dramatic sensory-motor deficit that challenges our CNS. Reconstruction of hand function is therefore not only an essential part of restoring body integrity and functional wholeness but also closes the loop of our neural circuits diminishing phantom sensation and neural pain. If biology fails to restore meaningful function, today we can resort to complex mechatronic replacement that have functional capabilities that in some respects even outperform biological alternatives, such as hand transplantation. As with replantation and transplantations, the challenge of bionic replacement is connecting the target with the CNS to achieve natural and intuitive control. In recent years, we have developed a number of strategies to improve neural interfacing, signal extraction, interpretation and stable mechanical attachment that are important parts of our current research. This work gives an overview of recent advances in bionic reconstruction, surgical refinements over technological interfacing, skeletal fixation, and modern rehabilitation tools that allow quick integration of prosthetic replacement.

Common Synaptic Input to Motor Neurons and Neural Drive to Targeted Reinnervated Muscles.

We compared the behavior of motor neurons innervating their physiological muscle targets with motor neurons from the same spinal segment whose axons were surgically redirected to remnant muscles (targeted muscle reinnervation). The objective was to assess whether motor neurons with nonphysiological innervation receive similar synaptic input and could be voluntary controlled as motor neurons with natural innervation. For this purpose, we acquired high-density EMG signals from the biceps brachii in 5 male transhumeral amputees who underwent targeted reinnervation of this muscle by the ulnar nerve and from the first dorsal interosseous muscle of 5 healthy individuals to investigate the natural innervation of the ulnar nerve. The same recordings were also performed from the biceps brachii muscle of additional 5 able-bodied individuals. The EMG signals were decomposed into discharges of motor unit action potentials. Motor neurons were progressively recruited for the full range of submaximal muscle activation in all conditions. Moreover, their discharge rate significantly increased from recruitment to target activation level in a similar way across the subject groups. Motor neurons across all subject groups received common synaptic input as identified by coherence analysis of their spike trains. However, the relative strength of common input in both the delta (0.5-5 Hz) and alpha (5-13 Hz) bands was significantly smaller for the surgically reinnervated motor neuron pool with respect to the corresponding physiologically innervated one. The results support the novel approach of motor neuron interfacing for prosthesis control and provide new insights into the role of afferent input on motor neuron activity.SIGNIFICANCE STATEMENT Targeted muscle reinnervation surgically redirects nerves that lost their target in the amputation into redundant muscles in the region of the stump. The study of the behavior of motor neurons following this surgery is needed for designing biologically inspired prosthetic control strategies. Moreover, targeted muscle reinnervation offers a human experimental framework for studying the control and behavior of motor neurons when changing their target innervated muscle fibers and sensory feedback. Here, we show that the control of motor neurons and their synaptic input, following reinnervation, was remarkably similar to that of the physiological innervation, although with reduced common drive at some frequencies. The results advance our knowledge on the role of sensory input in the generation of the neural drive to muscles and provide the basis for designing physiologically inspired methods for prosthesis control.

Recovery from muscle weakness by exercise and FES: lessons from Masters, active or sedentary seniors and SCI patients.

Many factors contribute to the decline of skeletal muscle that occurs as we age. This is a reality that we may combat, but not prevent because it is written into our genome. The series of records from World Master Athletes reveals that skeletal muscle power begins to decline at the age of 30 years and continues, almost linearly, to zero at the age of 110 years. Here we discuss evidence that denervation contributes to the atrophy and slowness of aged muscle. We compared muscle from lifelong active seniors to that of sedentary elderly people and found that the sportsmen have more muscle bulk and slow fiber type groupings, providing evidence that physical activity maintains slow motoneurons which reinnervate muscle fibers. Further, accelerated muscle atrophy/degeneration occurs with irreversible Conus and Cauda Equina syndrome, a spinal cord injury in which the human leg muscles may be permanently disconnected from the nervous system with complete loss of muscle fibers within 5-8 years. We used histological morphometry and Muscle Color Computed Tomography to evaluate muscle from these peculiar persons and reveal that contraction produced by home-based Functional Electrical Stimulation (h-bFES) recovers muscle size and function which is reversed if h-bFES is discontinued. FES also reverses muscle atrophy in sedentary seniors and modulates mitochondria in horse muscles. All together these observations indicate that FES modifies muscle fibers by increasing contractions per day. Thus, FES should be considered in critical care units, rehabilitation centers and nursing facilities when patients are unable or reluctant to exercise.

Bionic reconstruction to restore hand function after brachial plexus injury: a case series of three patients.

BACKGROUND: Brachial plexus injuries can permanently impair hand function, yet present surgical reconstruction provides only poor results. Here, we present for the first time bionic reconstruction; a combined technique of selective nerve and muscle transfers, elective amputation, and prosthetic rehabilitation to regain hand function. METHODS: Between April 2011, and May 2014, three patients with global brachial plexus injury including lower root avulsions underwent bionic reconstruction. Treatment occurred in two stages; first, to identify and create useful electromyographic signals for prosthetic control, and second, to amputate the hand and replace it with a mechatronic prosthesis. Before amputation, the patients had a specifically tailored rehabilitation programme to enhance electromyographic signals and cognitive control of the prosthesis. Final prosthetic fitting was applied as early as 6 weeks after amputation. FINDINGS: Bionic reconstruction successfully enabled prosthetic hand use in all three patients. After 3 months, mean Action Research Arm Test score increased from 5·3 (SD 4·73) to 30·7 (14·0). Mean Southampton Hand Assessment Procedure score improved from 9·3 (SD 1·5) to 65·3 (SD 19·4). Mean Disabilities of Arm, Shoulder and Hand score improved from 46·5 (SD 18·7) to 11·7 (SD 8·42). INTERPRETATION: For patients with global brachial plexus injury with lower root avulsions, who have no alternative treatment, bionic reconstruction offers a means to restore hand function. FUNDING: Austrian Council for Research and Technology Development, Austrian Federal Ministry of Science, Research & Economy, and European Research Council Advanced Grant DEMOVE.

Infection of mice with influenza A/WSN/33 (H1N1) virus alters alveolar type II cell phenotype.

Influenza viruses cause acute respiratory disease of great importance to public health. Alveolar type II (ATII) respiratory epithelial cells are central to normal lung function and are a site of influenza A virus replication in the distal lung. However, the consequences of infection for ATII cell function are poorly understood. To determine the impact of influenza infection on ATII cells we used C57BL/6-congenic SP-C(GFP) mice that express green fluorescent protein (GFP) under the control of the surfactant protein-C (SP-C) promoter, which is only active in ATII cells. Most cells isolated from the lungs of uninfected SP-C(GFP) mice were GFP(+) but did not express the alveolar type I (ATI) antigen podoplanin (PODO). ATII cells were also EpCAM(+) and α2,3-linked sialosaccharide(+). Infection with influenza A/WSN/33 virus caused severe hypoxemia and pulmonary edema. This was accompanied by loss of whole lung GFP fluorescence, reduced ATII cell yields, increased ATII cell apoptosis, reduced SP-C gene and protein expression in ATII cell lysates, and increased PODO gene and protein levels. Flow cytometry indicated that infection decreased GFP(+)/PODO(-) cells and increased GFP(-)/PODO(+) and GFP(-)/PODO(-) cells. Very few GFP(+)/PODO(+) cells were detectable. Finally, infection resulted in a significant decline in EpCAM expression by PODO(+) cells, but had limited effects on α2,3-linked sialosaccharides. Our findings indicate that influenza infection results in a progressive differentiation of ATII cells into ATI-like cells, possibly via an SP-C(-)/PODO(-) intermediate, to replace dying or dead ATI cells. However, impaired SP-C synthesis is likely to contribute significantly to reduced lung compliance in infected mice.

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control.

Nonlinear Mapping From EMG to Prosthesis Closing Velocity Improves Force Control With EMG Biofeedback.

When using EMG biofeedback to control the grasping force of a myoelectric prosthesis, subjects need to activate their muscles and maintain the myoelectric signal within an appropriate interval. However, their performance decreases for higher forces, because the myoelectric signal is more variable for stronger contractions. Therefore, the present study proposes to implement EMG biofeedback using nonlinear mapping, in which EMG intervals of increasing size are mapped to equal-sized intervals of the prosthesis velocity. To validate this approach, 20 non-disabled subjects performed force-matching tasks using Michelangelo prosthesis with and without EMG biofeedback with linear and nonlinear mapping. Additionally, four transradial amputees performed a functional task in the same feedback and mapping conditions. The success rate in producing desired force was significantly higher with feedback (65.4±15.9%) compared to no feedback (46.2±14.9%) as well as when using nonlinear (62.4±16.8%) versus linear mapping (49.2±17.2%). Overall, in non-disabled subjects, the highest success rate was obtained when EMG biofeedback was combined with nonlinear mapping (72%), and the opposite for linear mapping with no feedback (39.6%). The same trend was registered also in four amputee subjects. Therefore, EMG biofeedback improved prosthesis force control, especially when combined with nonlinear mapping, which showed to be an effective approach to counteract increasing variability of myoelectric signal for stronger contractions.

A Novel Sensory Feedback Approach to Facilitate Both Predictive and Corrective Control of Grasping Force in Myoelectric Prostheses.

Reliable force control is especially important when using myoelectric upper-limb prostheses as the force defines whether an object will be firmly grasped, damaged, or dropped. It is known from human motor control that the grasping of non-disabled subjects is based on a combination of anticipation and feedback correction. Inspired by this insight, the present study proposes a novel approach to provide artificial sensory feedback to the user of a myoelectric prosthesis using vibrotactile stimulation to facilitate both predictive and corrective processes characteristic of grasping in non-disabled people. Specifically, the level of EMG was conveyed to the subjects while closing the prosthesis (predictive strategy), whereas the actual grasping force was transmitted when the prosthesis closed (corrective strategy). To investigate if this combined EMG and force feedback is indeed an effective method to explicitly close the control loop, 16 non-disabled and 3 transradial amputee subjects performed a set of functional tasks, inspired by the "Box and Block" test, with six target force levels, in three conditions: no feedback, only EMG feedback, and combined feedback. The highest overall performance in non-disabled subjects was obtained with combined feedback (79.6±9.9%), whereas the lowest was achieved with no feedback (53±11.5%). The combined feedback, however, increased the task completion time compared to the other two conditions. A similar trend was obtained also in three amputee subjects. The results, therefore, indicate that the feedback inspired by human motor control is indeed an effective approach to improve prosthesis grasping in realistic conditions when other sources of feedback (vision and audition) are not blocked.

Gender and body mass index as risk factors for bladder perforation during primary transurethral resection of bladder tumors.

PURPOSE: Bladder cancer is the second most common tumor of the genitourinary system. Although transurethral resection is the standard diagnostic and therapeutic procedure, it is not morbidity free. Bladder perforation is the second most common complication and it can lead to severe further complications. We evaluated risk factors for bladder perforation in patients treated with transurethral resection of bladder tumors. MATERIALS AND METHODS: We retrospectively studied the records of 1,284 patients with bladder cancer who underwent transurethral resection of bladder tumors between 1986 and 2006. Data on risk factors for bladder perforation, including age, gender, body mass index, nicotine use, gross hematuria, transurethral catheterization, bladder stones, tumor stage and grade, number of tumors and resection weight, were analyzed with the chi-square or Fisher exact test. RESULTS: Of the 49 bladder perforations (3.8%) 89.8% were extraperitoneal and 10.2% were intraperitoneal. The risk of bladder perforation was associated with gender (female and male 7.2% and 2.6%, p <0.001), body mass index (less than 25, 25 to 30 and greater than 30 kg/m(2) 5.5%, 3.4% and 0.6%, p = 0.016), tumor stage (pTis, pTa, pT1 and pT2 or greater 3.7%, 2.6%, 4.5% and 6.7%, p = 0.049), infiltration depth (superficial and muscle invasive 3.2% and 6.6%, p = 0.023) and resection weight (less than 2.5 and 20 gm or greater 2.4% and 9.2%, respectively, p = 0.003). Patient age, nicotine use, gross hematuria at diagnosis, transurethral catheterization, bladder stones, number of tumors and tumor grade were not risk factors for bladder perforation. CONCLUSIONS: Aside from tumor characteristics female gender and low body mass index were risk factors for inadvertent bladder perforation during transurethral resection of bladder tumors. Each factor is readily apparent.

Linear Motor Driven Leg-Press Dynamometer for Testing, Training, and Rehabilitation: A Scoping Review with a Focus on the Concept of Serial Stretch Loading.

BACKGROUND: The purpose of this scoping review was to analyze the evidence of acute and long-term effects of the application of leg-press strength training with or without serial stretch-loading stimuli on various biomechanical and physiological outcomes. METHODS: This review was performed in accordance with PRISMA for Scoping Reviews recommendations, and two researchers independently searched the following databases: PubMed, Web of Science, Scopus, ScienceDirect, ProQuest, Cochrane, and Google Scholar. All studies that used unique leg-press device for testing, acute responses and long-term adaptation were included in this review, irrespective of the measured outcomes. A total of 13 studies were included in this review, with 5 focused on the testing capabilities of the device and acute training responses and 8 focused on the long-term adaptations in various physical and physiological outcomes. RESULTS: Regarding the acute responses after leg-press strength training with or without serial stretch-loading stimuli, visible changes were observed in the muscle force, rate of force development, and hormonal concentrations between pre- and postmenopausal women (only one study). Long-term studies revealed different training adaptations after performing leg-press strength training with unique serial stretch-loading stimuli. A positive trend for leg-press strength training with serial stretch-loading was recorded in the young population and athletes; however, more variable training effects favoring one or the other approach were achieved in the older population. CONCLUSIONS: In summary, this review shows the uniqueness and usability of a leg-press device that is capable of various exercising modes, including special serial stretch-loading stimuli. The use of this device can serve as a positive addition to training regiments, and the main application appears to be suitable for rehabilitation needs.

Trauma of Peripheral Innervation Impairs Content of Epidermal Langerhans Cells.

Langerhans cells represent the first immune cells that sense the entry of external molecules and microorganisms at the epithelial level in the skin. In this pilot case-study, we evaluated Langerhans cells density and progression of epidermal atrophy in permanent spinal cord injury (SCI) patients suffering with either lower motor neuron lesions (LMNSCI) or upper motor neuron lesions (UMNSCI), both submitted to surface electrical stimulation. Skin biopsies harvested from both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation for denervated degenerating muscles (DDM) delivered at home (h-bFES) by large anatomically shaped surface electrodes placed on the skin of the anterior thigh in the cases of LMNSCI patients or by neuromuscular electrical stimulation (NMES) for innervated muscles in the cases of UMNSCI persons. Using quantitative histology, we analyzed epidermal thickness and flattening and content of Langerhans cells. Linear regression analyses show that epidermal atrophy worsens with increasing years of LMNSCI and that 2 years of skin electrostimulation reverses skin changes, producing a significant recovery of epidermis thickness, but not changes in Langerhans cells density. In UMNSCI, we did not observe any statistically significant changes of the epidermis and of its content of Langerhans cells, but while the epidermal thickness is similar to that of first year-LMNSCI, the content of Langerhans cells is almost twice, suggesting that the LMNSCI induces an early decrease of immunoprotection that lasts at least 10 years. All together, these are original clinically relevant results suggesting a possible immuno-repression in epidermis of the permanently denervated patients.

Safe neuromuscular electrical stimulator designed for the elderly.

A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.

Objectively Measured Physical Activity, Sedentary Behavior and Functional Performance before and after Lower Limb Joint Arthroplasty: A Systematic Review with Meta-Analysis.

Patients after joint arthroplasty tend to be less physically active; however, studies measuring objective physical activity (PA) and sedentary behavior (SB) in these patients provide conflicting results. The aim of this meta-analysis was to assess objectively measured PA, SB and performance at periods up to and greater than 12 months after lower limb arthroplasty. Two electronic databases (PubMed and Medline) were searched to identify prospective and cross-sectional studies from 1 January 2000 to 31 December 2020. Studies including objectively measured SB, PA or specific performance tests in patients with knee or hip arthroplasty, were included in the analyses both pre- and post-operatively. The risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN). After identification and exclusion, 35 studies were included. The data were analyzed using the inverse variance method with the random effects model and expressed as standardized mean difference and corresponding 95% confidence intervals. In total, we assessed 1943 subjects with a mean age of 64.9 (±5.85). Less than 3 months post-operative, studies showed no differences in PA, SB and performance. At 3 months post-operation, there was a significant increase in the 6 min walk test (6MWT) (SMD 0.65; CI: 0.48, 0.82). After 6 months, changes in moderate to vigorous physical activity (MVPA) (SMD 0.33; CI: 0.20, 0.46) and the number of steps (SMD 0.45; CI: 0.34, 0.54) with a large decrease in the timed-up-and-go test (SMD -0.61; CI: -0.94, -0.28) and increase in the 6MWT (SMD 0.62; CI: 0.26-0.98) were observed. Finally, a large increase in MVPA (SMD 0.70; CI: 0.53-0.87) and a moderate increase in step count (SMD 0.52; CI: 0.36, 0.69) were observed after 12 months. The comparison between patients and healthy individuals pre-operatively showed a very large difference in the number of steps (SMD -1.02; CI: -1.42, -0.62), but not at 12 months (SMD -0.75; -1.89, 0.38). Three to six months after knee or hip arthroplasty, functional performance already exceeded pre-operative levels, yet PA levels from this time period remained the same. Although PA and functional performance seemed to fully restore and exceed the pre-operation levels at six to nine months, SB did not. Moreover, PA remained lower compared to healthy individuals even longer than twelve months post-operation. Novel rehabilitation protocols and studies should focus on the effects of long-term behavioral changes (increasing PA and reducing SB) as soon as functional performance is restored.