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Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using adeno-associated vector 9 (AAV9) and AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying disease course in a mouse model of MLIV by the human MCOLN1 gene transfer. Here, using a primate-enabling capsid AAV.CPP.16 (CPP16), we constructed a new, clinic-oriented MCOLN1 gene expression vector and demonstrated its efficacy in the preclinical model of MLIV. Systemic administration of CPP16-MCOLN1 in adult symptomatic Mcoln1−/− mice at a dose of 1e12 vg per mouse resulted in MCOLN1 expression in the brain and peripheral tissues, alleviated brain pathology, rescued neuromotor function, and completely prevented paralysis. Notable expression of MCOLN1 transcripts was also detected in the retina of the mouse, which had exhibited significant degeneration at the time of the treatment. However, no increase in retinal thickness was observed after gene therapy treatment. Our results suggest a new AAV-based systemic gene replacement therapy for the treatment of MLIV that could be translated into clinical studies.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) is an emerging approach to cardiac arrest. We present two contrasting cases from a high-volume extracorporeal membrane oxygenation (ECMO) center (defined as greater than 30 ECMO cases per year) without a 24/7 ECPR program to highlight how to establish an ECPR program with a focus on patient selection and outcome optimization. In one case, a patient presented with cardiac arrest during initial triage for chest pain within the emergency department, and in the other case, a patient experienced an out-of-hospital cardiac arrest with prolonged no-flow and low-flow time. Despite the lack of a 24/7 ECPR program at the presenting center, both patients received an ECPR evaluation, as both patients presented while all services necessary for ECMO cannulation were available. The in-hospital cardiac arrest patient was successfully cannulated for ECMO during cardiopulmonary resuscitation and survived with few complications. The out-of-hospital cardiac arrest patient was deemed a poor candidate for ECPR and expired soon after presentation. These two cases highlight the complex decision-making in ECPR and further illustrate how to create ECPR protocols at a high-volume ECMO center before resources are available for a 24/7 ECPR program.

Background: The direct lateral (DL) approach to total hip arthroplasty is more commonly used than the newer direct anterior (DA) approach. Both approaches use collared or collarless femoral stems. We sought to assess implant stability of stem designs implanted with the DL approach and compare outcomes from this cohort with those of a previously reported cohort of patients who underwent arthroplasty with a DA approach. We also sought to determine if early recovery influences differences in migration. Methods: Patients underwent total hip arthroplasty using the DL or the DA approach and were randomized to receive either a collared or collarless, cementless femoral stem. On the day of surgery and at 6 follow-up visits through to 1 year, patients underwent supine radiostereometric imaging to track implant migration. At follow-up visits, patients performed an instrumented walking test to assess their functional ability and logged an average daily step count to assess their activity levels. We assessed whether patient function and activity were correlated with migration. Results: Stem design did not have a significant effect on migration for the DL group (p = 0.894). Compared with the DA group, the DL group migrated significantly less for both collared (p = 0.031) and collarless (p = 0.002) stems. Migration was not correlated with function or activity at any time point (p > 0.05). Conclusion: Most implant migration occurred from the day of surgery to 2 weeks after the operation and stabilized thereafter, suggesting adequate fixation and a low risk for aseptic loosening in both patient groups. Contexte : La voie laterale directe (LD) est utilisee plus frequemment pour effectuer une arthroplastie totale de la hanche (ATH) que la voie anterieure directe (AD), plus recente. Les 2 approches utilisent des tiges femorales avec ou sans collerette. Nous avons evalue la stabilite des modeles de tiges implantes par voie LD et compare les issues de cette cohorte a celles d'une cohorte de patients ayant deja fait l'objet d'une etude qui avaient subi une arthroplastie par voie AD. Nous avons aussi cherche a determiner si le debut du retablissement avait une influence sur des differences dans le risque de migration. Methodes : Des patients devant subir une arthroplastie par voie LD ou AD ont ete repartis aleatoirement en 2 groupes : tiges femorales sans ciment avec ou sans collerette. Le jour de l'intervention et durant 6 visites de suivi la premiere annee, les patients ont subi un examen d'imagerie radiostereometrique en decubitus visant a mesurer la migration de l'implant. Durant les visites de suivi, ils ont fait un test de marche instrumente visant a evaluer leur capacite fonctionnelle et enregistre leur nombre moyen de pas quotidiens, ce qui permet d'evaluer leur niveau d'activite. Nous avons cherche a determiner s'il y avait une correlation entre la migration observee, et la capacite fonctionnelle et le niveau d'activite des patients. Resultats : Le modele de tige n'a pas eu d'effet significatif sur la migration pour le groupe LD (p = 0,894). Par contre, comparativement au groupe AD, on a enregistre chez les patients du groupe LD une migration significativement inferieure pour les tiges avec collerette (p = 0,031) et sans collerette (p = 0,002). Aucune correlation n'a ete observee entre la migration et la capacite fonctionnelle ou le niveau d'activite, peu importe le moment de l'evaluation (p > 0,05). Conclusion : L'essentiel de la migration des implants est survenu dans les 2 semaines suivant l'intervention, puis le processus s'est stabilise, ce qui semble indiquer une fixation adequate et un faible risque de descellement aseptique dans les 2 groupes de patients., Total hip arthroplasty (THA) is the only viable treatment for patients with end-stage osteoarthritis of the hip, and is successful and reliable in improving patients' quality of life, restoring function [...]

IntroductionThe rise of soft robotics has driven the development of devices for assistance in activities of daily living (ADL). Likewise, different types of actuation have been developed for safer human interaction. Recently, textile-based pneumatic actuation has been introduced in hand exoskeletons for features such as biocompatibility, flexibility, and durability. These devices have demonstrated their potential use in assisting ADLs, such as the degrees of freedom assisted, the force exerted, or the inclusion of sensors. However, performing ADLs requires the use of different objects, so exoskeletons must provide the ability to grasp and maintain stable contact with a variety of objects to lead to the successful development of ADLs. Although textile-based exoskeletons have demonstrated significant advancements, the ability of these devices to maintain stable contact with a variety of objects commonly used in ADLs has yet to be fully evaluated.Materials and methodsThis paper presents the development and experimental validation in healthy users of a fabric-based soft hand exoskeleton through a grasping performance test using The Anthropomorphic Hand Assessment Protocol (AHAP), which assesses eight types of grasping with 24 objects of different shapes, sizes, textures, weights, and rigidities, and two standardized tests used in the rehabilitation processes of post- stroke patients.Results and discussionA total of 10 healthy users (45.50 ± 14.93 years old) participated in this study. The results indicate that the device can assist in developing ADLs by evaluating the eight types of grasps of the AHAP. A score of 95.76 ± 2.90% out of 100% was obtained for the Maintaining Score, indicating that the ExHand Exoskeleton can maintain stable contact with various daily living objects. In addition, the results of the user satisfaction questionnaire indicated a positive mean score of 4.27 ± 0.34 on a Likert scale ranging from 1 to 5.

Muscle fatigue is defined as a reduced ability to maintain maximal strength during voluntary contraction. It is associated with musculoskeletal disorders that affect workers performing repetitive activities, affecting their performance and well-being. Although electromyography remains the gold standard for measuring muscle fatigue, its limitations in long-term work motivate the use of wearable devices. This article proposes a computational model for estimating muscle fatigue using wearable and non-invasive devices, such as Optical Fiber Sensors (OFSs) and Inertial Measurement Units (IMUs) along the subjective Borg scale. Electromyography (EMG) sensors are used to observe their importance in estimating muscle fatigue and comparing performance in different sensor combinations. This study involves 30 subjects performing a repetitive lifting activity with their dominant arm until reaching muscle fatigue. Muscle activity, elbow angles, and angular and linear velocities, among others, are measured to extract multiple features. Different machine learning algorithms obtain a model that estimates three fatigue states (low, moderate and high). Results showed that between the machine learning classifiers, the LightGBM presented an accuracy of 96.2% in the classification task using all of the sensors with 33 features and 95.4% using only OFS and IMU sensors with 13 features. This demonstrates that elbow angles, wrist velocities, acceleration variations, and compensatory neck movements are essential for estimating muscle fatigue. In conclusion, the resulting model can be used to estimate fatigue during heavy lifting in work environments, having the potential to monitor and prevent muscle fatigue during long working shifts.

Abstract The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760–1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

Contextual design and selection of MRI protocols is critical for making an accurate diagnosis given the wide variety of clinical indications for spine imaging in children. Here, we describe our pediatric spine imaging protocols in detail, tailored to specific clinical questions.

Abstract There have been nearly 70 million cases of COVID‐19 worldwide, with over 1.5 million deaths at the time of this publication. This global pandemic has mandated dramatic changes in healthcare delivery with a particular focus on social distancing in order to reduce viral transmission. Heart failure patients are among the highest utilizers of health care and are at increased risk for COVID‐related vulnerabilities. Effectively managing this complex and resource‐intensive patient population from a distance presents new and unique challenges. Here, we review relevant data on telemedicine and remote monitoring strategies for heart failure patients and provide a framework to help providers treat this population during the COVID‐19 pandemic. This includes (i) dedicated pre‐visit contact and planning (i.e. confirm clinical appropriateness, presence of compatible technology, and patient comfort); (ii) utilization of virtual clinic visits (use of telehealth platforms, a video‐assisted exam, self‐reported vital signs, and weights); and (iii) use of existing remote heart failure monitoring sensors when applicable (CardioMEMS, Optivol, and HeartLogic). While telemedicine and remote monitoring strategies are not new, these technologies are emerging as an important tool for the effective management of heart failure patients during the COVID‐19 pandemic. In general, these strategies appear to be safe; however, additional data will be needed to determine their effectiveness with respect to both process and outcomes measures.

This paper presents the development of an intelligent soft-sensor system to add haptic perception to the underactuated hand prosthesis PrHand. Two sensors based on optical fiber were constructed, one for finger joint angles and the other for fingertips’ contact force. Three sensor fabrications were tested for the angle sensor by axially rotating the sensors in four positions. The configuration with the most similar response in the four rotations was chosen. The chosen sensors presented a polynomial response with R2 higher than 92%. The tactile force sensors tracked the force made over the objects. Almost all sensors presented a polynomial response with R2 higher than 94%. The system monitored the prosthesis activity by recognizing grasp types. Six machine learning algorithms were tested: linear regression, k-nearest neighbor, support vector machine, decision tree, k-means clustering, and hierarchical clustering. To validate the algorithms, a k-fold test was used with a k = 10, and the accuracy result for k-nearest neighbor was 98.5%, while that for decision tree was 93.3%, enabling the classification of the eight grip types.

Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

Purpose In the accompanying article, “Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe,” we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.

Purpose Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.