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In recognition of the importance and timeliness of computational models for accelerating progress in neurorehabilitation, the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) sponsored a conference in March 2023 at the University of Southern California that drew global participation from engineers, scientists, clinicians, and trainees. This commentary highlights promising applications of computational models to understand neurorehabilitation ("Using computational models to understand complex mechanisms in neurorehabilitation" section), improve rehabilitation care in the context of digital twin frameworks ("Using computational models to improve delivery and implementation of rehabilitation care" section), and empower future interdisciplinary workforces to deliver higher-quality clinical care using computational models ("Using computational models in neurorehabilitation requires an interdisciplinary workforce" section). The authors describe near-term gaps and opportunities, all of which encourage interdisciplinary team science. Four major opportunities were identified including (1) deciphering the relationship between engineering figures of merit-a term commonly used by engineers to objectively quantify the performance of a device, system, method, or material relative to existing state of the art-and clinical outcome measures, (2) validating computational models from engineering and patient perspectives, (3) creating and curating datasets that are made publicly accessible, and (4) developing new transdisciplinary frameworks, theories, and models that incorporate the complexities of the nervous and musculoskeletal systems. This commentary summarizes U.S. funding opportunities by two Federal agencies that support computational research in neurorehabilitation. The NSF has funding programs that support high-risk/high-reward research proposals on computational methods in neurorehabilitation informed by theory- and data-driven approaches. The NIH supports the development of new interventions and therapies for a wide range of nervous system injuries and impairments informed by the field of computational modeling. The conference materials can be found at https://dare2023.usc.edu/ ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Participation refers to a state of health in which a person is able to fully engage in roles and life situations. Adults living with and beyond cancer often report persistent participation restrictions that affect their productivity and quality of life. The American Occupational Therapy Foundation convened a group of scientists from seven different disciplines in a Planning Grant Collective (PGC) to stimulate research to identify scalable ways to preserve and optimize participation among cancer survivors. Participants identified challenges, prioritized solutions, and generated novel research questions that move beyond symptom and impairment mitigation as outcomes to identify interventions that improve participation in roles and life situations. This article summarizes the PGC discussion and recommendations regarding three challenges: (a) the dynamic and multi-faceted nature of participation, (b) a need to integrate the concept of participation within the culture of oncology, and (c) identification of priority areas in which new lines of research regarding participation would be most impactful.

Cancer rehabilitation research has accelerated as great attention has focused on improving survivorship care. Recent expert consensus has attempted to prioritize research needs and suggests greater focus on studying physical functioning of survivors. However, no analysis of the publication landscape has substantiated these proposed needs. This manuscript provides an analysis of PubMed indexed articles related to cancer rehabilitation published between 1992 and 2017. A total of 22 171 publications were analyzed using machine learning and text analysis to assess publication metrics, topic areas of emphasis, and their interrelationships through topic similarity networks. Publications have increased at a rate of 136 articles per year. Approximately 10% of publications were funded by the National Institutes of Health institutes and centers, with the National Cancer Institute being the most prominent funder. The greatest volume and rate of publication increase were in the topics of Cognitive and Behavioral Therapies and Psychological Interventions, followed by Depression and Exercise Therapy. Four research topic similarity networks were identified and provide insight on areas of robust publication and notable deficits. Findings suggest that publication emphasis has strongly supported cognitive, behavioral, and psychological therapies; however, studies of functional morbidity and physical rehabilitation research are lacking. Three areas of publication deficits are noted: research on populations outside of breast, prostate, and lung cancers; methods for integrating physical rehabilitation services with cancer care, specifically regarding functional screening and assessment; and physical rehabilitation interventions. These deficits align with the needs identified by expert consensus and support the supposition that future research should emphasize a focus on physical rehabilitation.

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407., (Copyright © Wolters Kluwer Health, Inc. 2017.)

The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer survivors. These recommendations aim to enable future collaborations among a variety of stakeholders to improve the delivery of high-quality cancer care., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Agrin induces discrete high-density patches of acetylcholine receptors (AChRs) and other synaptic components on cultured myotubes in a manner that resembles synaptic differentiation. Furthermore, agrin-like molecules are present at developing neuromuscular junctions in vivo. This provides us with a unique opportunity to manipulate AChR patching in order to examine the role of cytoskeletal components. Cultured chick myotubes were fixed and labeled to visualize the distributions of actin, alpha-actinin, filamin, tropomyosin, and vinculin. Overnight exposure to agrin caused a small amount of alpha-actinin, filamin, and vinculin to reorganize into discrete clusters. Double-labeling studies revealed that 78% of the AChR clusters were associated with detectable concentrations of filamin, 70% with alpha-actinin, and 58% with vinculin. Filamin even showed congruence to AChRs within clustered regions. By contrast, actin (visualized with fluorescein-phalloidin) and tropomyosin did not show specific associations with agrin-induced AChR clusters. The accumulation of cytoskeletal components at AChRs clusters raised the possibility that cytoskeletal rearrangements direct AChR clustering. However, a time course of agrin-induced clustering that focused on filamin revealed that most of the early AChR clusters (3-6 h) were not associated with detectable amounts of cytoskeletal material. The accumulation of cytoskeletal material at later times (12-18 h) may imply a role in maintenance and stabilization, but it appears unlikely that these cytoskeletal elements initiate AChR clustering on myotubes.

Count-based scintigraphic left ventricular end-diastolic (LVED) volume measurement was optimized using a reproducible method for determining left ventricular counts and an independently measured average apparent tissue attenuation coefficient (0.16 cm-1). Tissue depth was calculated by triangulation. Results were compared to single-plane contrast ventriculographic volumes by an area-length method, performed within one hour, in 18 patients. The overall correlation of measurements of LVED volume by the 2 methods was 0.96 with standard error of the scintigraphic estimate of 15.8 ml. For 6 patients with angiographically normal wall motion, the correlation of volume measurements was 0.99 with standard error of the estimate of 5.1 ml. The mean absolute difference in LVED volume by the 2 methods was 3.8 ml in the group with normal wall motion compared to 19.2 ml in the 12 patients with angiographically abnormal wall motion. Area-length LVED volume calculation assumes that the left ventricle conforms to a standard shape. Discrepancies in volume estimates with abnormal ventricular wall motion suggest that the area-length method is less accurate. Optimized count-based LVED left ventricular volume measurement is accurate and might be preferable to single-plane contrast angiographic volume measurement of abnormal ventricles.

Basal lamina-rich extracts of Torpedo californica electric organ contain a factor that causes acetylcholine receptors (AChRs) on cultured myotubes to aggregate into patches. Our previous studies have indicated that the active component of these extracts is similar to the molecules in the basal lamina which direct the aggregation of AChRs in the muscle fibre plasma membrane at regenerating neuromuscular junctions in vivo. Because it can be obtained in large amounts and assayed in controlled conditions in cell culture, the AChR-aggregating factor from electric organ may be especially useful for examining in detail how the postsynaptic apparatus of regenerating muscle is assembled. Here we demonstrate that the electric organ factor causes not only the formation of AChR aggregates on cultured myotubes, but also the formation of patches of acetylcholinesterase (AChE). This finding, together with the observation that basal lamina directs the formation of both AChR and AChE aggregates at regenerating neuromuscular junctions in vivo, leads us to hypothesize that a single component of the synaptic basal lamina causes the formation of both these synaptic specializations on regenerating myofibres.

Results of experiments outlined here provide evidence that components of the myofiber basal lamina sheath direct the formation of active zones in regenerating motor nerve terminals and the development of infoldings and the aggregation of AChRs in the plasma membrane of regenerating myofibers. As a step toward identifying the basal lamina molecules that aggregate AChRs, we are now studying an ECM fraction from the Torpedo electric organ that causes AChRs to aggregate on cultured myotubes. We have solubilized and purified the electric organ AChR-aggregating molecules over 1000-fold. Only nanogram amounts of the most purified extracts are required to cause detectable AChR aggregation. We have also shown that similar activity can be extracted in relatively small amounts from muscle. Antiserum raised against the partially purified electric organ material completely blocked and immunoprecipitated the AChR-aggregating activity in extracts of the electric organ and muscle and bound to components of the basal lamina of frog muscle fibers. Although several polypeptides are present in our most purified extracts, an antiserum against polypeptides in the range of 80 kD completely blocked AChR aggregation by soluble extracts of the electric organ. These findings demonstrate the feasibility of isolating molecules from the synapse-rich electric organ that cause AChR aggregation and comparing them by immunological techniques with those in basal lamina at the neuromuscular junction.

A protein neurotoxin (Bgt 3.1) present as a minor component in the venom of Bungarus multicinctus has been shown previously to block acetylcholine (ACh) sensitivity on chick ciliary ganglion (CG) neurons in cell culture. Alpha-bungarotoxin (Bgt. 2.2) binds to the neurons but does not block ACh sensitivity; the function of the Bgt. 2.2 binding site is unknown. The present studies demonstrate that Bgt 3.1 can induce the rapid internalization of Bgt 2.2 bound on the surface of CG and sympathetic neurons. The rapid internalization of bound Bgt 2.2 caused by Bgt. 3.1 can be seen with fluoresence microscopy using rhodamine-labeled Bgt 2.2 as the probe and by immunological techniques using anti-Bgt 2.2 antiserum to locate the bound 125I-Bgt 2.2. The rapid internalization is blocked by low temperature or by high concentrations of Bgt 2.2 and is not induced by Bgt 2.2 itself or by small cholinergic ligands. Bound 125I-Bgt 2.2 is released into the medium as degraded material after internalization is induced. Bgt 3.1 does not induce internalization of Bgt 2.2 bound to skeletal myotubes in culture nor does it induce the internalizaton of rhodamine-labeled nerve growth factor bound to sympathetic neurons, suggesting that its effect on neuronally bound Bgt 2.2 might be a specific one. Competition binding studies suggest that Bgt 3.1 may trigger the internalization of bound Bgt 2.2 by direct interaction with a Bgt 2.2 binding site. The effect of Bgt 3.1 on neuronal ACh sensitivity, however, does not depend on internalization of Bgt 2.2 binding sites since full inhibition of ACh sensitivity is still achieved by Bgt 3.1 under conditions where internalization is blocked. Neurons may have more than one class of Bgt 2.2 on the neurons. The internalization of Bgt 2.2 binding sites induced by Bgt 3.1 provides an unusual opportunity to study cellular mechanisms by which neurons can regulate the number and distribution of their surface components.

The basal lamina in the synaptic cleft of the vertebrate skeletal neuromuscular junction contains molecules that direct the formation of synaptic specializations in regenerating axons and muscle fibres. We have undertaken a series of experiments aimed at identifying and characterizing the molecules responsible for the formation of one of these specializations, the aggregates of acetylcholine receptors (AChRs) in the muscle fibre plasma membrane. We began by preparing an insoluble, basal lamina-containing fraction from Torpedo californica electric organ, a tissue which has a far higher concentration of cholinergic synapses than muscle, and showing that this fraction caused AChRs on cultured chick myotubes to aggregate. A critical step is learning whether or not the electric organ factor is similar to the receptor-aggregating molecule in the basal lamina at the neuromuscular junction. The importance of this problem is emphasized by reports that clearly non-physiological agents, such as positively charged latex beads, can cause AChR aggregation on cultured muscle cells. We have already shown that Torpedo muscle contains an AChR-aggregating factor similar to that of electric organ, although in much lower amounts. Here we demonstrate, using monoclonal antibodies, that the AChR-aggregating factor in our extracts of electric organ is, in fact, antigenically related to molecules concentrated in the synaptic cleft at the neuromuscular junction.

A cardiac transplant patient with rapidly progressive graft atherosclerosis is described. This case demonstrates the accelerated nature of this disease and problems in diagnosis, as well as an unexpected and previously unreported lack of sensitivity of exercise thallium scintigraphy in its investigation. This case also gives further support to the practice of routinely and frequently obtaining coronary arteriograms in the management of these patients.

Fifty adolescents, 12-17 years of age, were treated for obesity from 1967 to 1972. They were contacted in 1977 to obtain follow-up data. Each subject had been treated in a program of dietary counseling and behavior modification. Mean weight on follow-up was 18.1 lb (8.2 kg) lower than mean initial weight (P less than 0.05). The mean decrease over desired weight was 29.5%. Twenty-two patients reported a weight loss of greater than 20 lb (P greater than 0.001). (9.1 kg) and 15 patients reported a weight loss of 0-20 lb (9.1 kg). Thirty-eight percent of the patient were no longer obese (greater than 20% over ideal body weight) and an additional 22% were no longer overweight (10-20% over ideal body weight). These results suggest that a dietary and behavior modification program offered to adolescents may show beneficial results in young adulthood.

Hypnotherapy is a method of treatment for resistant obesity. This study was undertaken to ascertain the efficacy and/or risks it holds for adolescents. All tended to see hypnosis as a quick solution to longstanding problems. Other forms of weight control therapy had been unsuccessful. Untoward reactions occurred in many teenagers. These included: dissociated state, depersonalization, anxiety and fears. Patients who were not in a deep state of hypnosis were disappointed and viewed this as another failure experience. The severe side effects were observed in those patients in the earlier developmental phases of adolescence.