Protocol for a randomized controlled trial of brief behavioral activation among older adult cancer survivors.

INTRODUCTION: As many as 35% of older adult cancer survivors (OACS; i.e., ≥65 years old) have clinically significant depression. OACS often experience fatigue, mild cognitive impairment, and increased medical comorbidities post-cancer that make them susceptible to depression. Behavioral activation (BA) is an empirically supported depression treatment in geriatric psychiatry that guides individuals to reengage in pleasurable and rewarding activities and has great potential for addressing the needs of OACS. This manuscript presents the protocol for a pilot randomized controlled trial (RCT) testing the efficacy of a brief BA intervention adapted to address the needs of OACS (BBA-OACS) by telephone and videoconference delivery. MATERIALS AND METHODS: An RCT will be conducted at Memorial Sloan Kettering Cancer Center (MSK) in New York City. Participants will be randomized to either BA as a target intervention or supportive psychotherapy (SP) as a standard of care control intervention for outpatient oncology. The target intervention includes 10 weekly sessions of BA consisting of psychoeducation about depression and the rationale for BA, life areas and values assessment, compilation of a list of enjoyable and important activities across values, activity scheduling, and self-monitoring of satisfaction and mood. The standard of care control intervention includes 10 weekly sessions of SP consisting of reassurance, guidance, encouragement, and support for patients with cancer. OACS who have a history of cancer, report elevated depressive symptoms, are fluent in English, and can communicate via telephone or videoconference will be recruited from the MSK Survivorship Clinics across all disease types. Seventy participants will be recruited for the study (10 training cases, 30 in each RCT arm). The primary aim is to evaluate implementation outcomes (i.e., acceptability, feasibility, and fidelity) of BA, relative to SP, for cancer survivorship. The secondary aim is to determine the preliminary effects of BA on depressive symptoms (primary outcome), anxiety, coping, and increased activity level (secondary outcomes) compared to SP. Participants will be asked to complete a set of three surveys pre- and post-intervention. DISCUSSION: If successful, BBA-OACS would provide frontline clinicians with an accessible, evidence-based treatment for OACS. Future research will evaluate the efficacy of BA in a larger trial and its impact on depression and other healthcare outcomes. TRIAL REGISTRATION: This study is registered under ClinicalTrials.gov (ID NCT05574127).

Conductive gradient hydrogels allow spatial control of adult stem cell fate.

Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.

Wirelessly Powered-Electrically Conductive Polymer System for Stem Cell Enhanced Stroke Recovery.

Effective stroke recovery therapeutics remain limited. Stem cell therapies have yielded promising results, but the harsh ischemic environment of the post-stroke brain reduces their therapeutic potential. Previously, we developed a conductive polymer scaffold system that enabled stem cell delivery with simultaneous electrical modulation of the cells and surrounding neural environment. This wired polymer scaffold proved efficacious in optimizing ideal conditions for stem cell mediated motor improvements in a rodent model of stroke. To further enable preclinical studies and enhance translational potential, we identified a method to improve this system by eliminating its dependence upon a tethered power source. We have herein developed a wirelessly powered, electrically conductive polymer system that eases therapeutic application and enables full mobility. As a proof of concept, we demonstrate that the wirelessly powered scaffold is able to stimulate neural stem cells in vitro, as well as in vivo in a rodent model of stroke. This system modulates the stroke microenvironment and increases the production of endogenous stem cells. In summation, this novel, wirelessly powered conductive scaffold can serve as a mobile platform for a wide variety of therapeutics involving electrical stimulation.

Telehealth-Based Music Therapy Versus Cognitive Behavioral Therapy for Anxiety in Cancer Survivors: Rationale and Protocol for a Comparative Effectiveness Trial.

BACKGROUND: Cancer survivors represent one of the fastest growing populations in the United States. Unfortunately, nearly 1 in 3 survivors experience anxiety symptoms as a long-term consequence of cancer and its treatment. Characterized by restlessness, muscle tension, and worry, anxiety worsens the quality of life; impairs daily functioning; and is associated with poor sleep, depressed mood, and fatigue. Although pharmacological treatment options are available, polypharmacy has become a growing concern for cancer survivors. Music therapy (MT) and cognitive behavioral therapy (CBT) are evidence-based, nonpharmacological treatments that have demonstrated effectiveness in treating anxiety symptoms in cancer populations and can be adapted for remote delivery to increase access to mental health treatments. However, the comparative effectiveness of these 2 interventions delivered via telehealth is unknown. OBJECTIVE: The aims of the Music Therapy Versus Cognitive Behavioral Therapy for Cancer-related Anxiety (MELODY) study are to determine the comparative effectiveness of telehealth-based MT versus telehealth-based CBT for anxiety and comorbid symptoms in cancer survivors and to identify patient-level factors associated with greater anxiety symptom reduction for MT and CBT. METHODS: The MELODY study is a 2-arm, parallel-group randomized clinical trial that aims to compare the effectiveness of MT versus CBT for anxiety and comorbid symptoms. The trial will enroll 300 English- or Spanish-speaking survivors of any cancer type or stage who have experienced anxiety symptoms for at least 1 month. Participants will receive 7 weekly sessions of MT or CBT delivered remotely via Zoom (Zoom Video Communications, Inc) over 7 weeks. Validated instruments to assess anxiety (primary outcome), comorbid symptoms (fatigue, depression, insomnia, pain, and cognitive dysfunction), and health-related quality of life will be administered at baseline and at weeks 4, 8 (end of treatment), 16, and 26. Semistructured interviews will be conducted at week 8 with a subsample of 60 participants (30 per treatment arm) to understand individual experiences with the treatment sessions and their impact. RESULTS: The first study participant was enrolled in February 2022. As of January 2023, 151 participants have been enrolled. The trial is expected to be completed by September 2024. CONCLUSIONS: This study is the first and largest randomized clinical trial to compare the short- and long-term effectiveness of remotely delivered MT and CBT for anxiety in cancer survivors. Limitations include the lack of usual care or placebo control groups and the lack of formal diagnostic assessments for psychiatric disorders among trial participants. The study findings will help guide treatment decisions for 2 evidence-based, scalable, and accessible interventions to promote mental well-being during cancer survivorship. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46281.

Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke.

Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.

Electrical stimulation of human neural stem cells via conductive polymer nerve guides enhances peripheral nerve recovery.

Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances the efficacy of human neural progenitor cells (hNPCs) in treating a sciatic nerve transection in rats. Electrical stimulation strengthened the therapeutic potential of NPCs by upregulating gene expression of neurotrophic factors which are critical in augmenting synaptic remodeling, nerve regeneration, and myelination. Electrically-stimulated hNPC-containing CNGs are significantly more effective in improving sensory and motor functions starting at 1-2 weeks after treatment than either treatment alone. Electrophysiology and muscle assessment demonstrated successful re-innervation of the affected target muscles in this group. Furthermore, histological analysis highlighted an increased number of regenerated nerve fibers with thicker myelination in electrically-stimulated hNPC-containing CNGs. The elevated expression of tyrosine kinase receptors (Trk) receptors, known to bind to neurotrophic factors, indicated the long-lasting effect from electrical stimulation on nerve regeneration and distal nerve re-innervation. These data suggest that electrically-enhanced stem cell-based therapy provides a regenerative rehabilitative approach to promote peripheral nerve regeneration and functional recovery.

Conducting polymer-based granular hydrogels for injectable 3D cell scaffolds.

Injectable 3D cell scaffolds possessing both electrical conductivity and native tissue-level softness would provide a platform to leverage electric fields to manipulate stem cell behavior. Granular hydrogels, which combine jamming-induced elasticity with repeatable injectability, are versatile materials to easily encapsulate cells to form injectable 3D niches. In this work, we demonstrate that electrically conductive granular hydrogels can be fabricated via a simple method involving fragmentation of a bulk hydrogel made from the conducting polymer PEDOT:PSS. These granular conductors exhibit excellent shear-thinning and self-healing behavior, as well as record-high electrical conductivity for an injectable 3D scaffold material (~10 S m-1). Their granular microstructure also enables them to easily encapsulate induced pluripotent stem cell (iPSC)-derived neural progenitor cells, which were viable for at least 5 days within the injectable gel matrices. Finally, we demonstrate gel biocompatibility with minimal observed inflammatory response when injected into a rodent brain.

Functional analysis and generalized treatment of disruptive behavior during dental exams.

Patient disruption during dental visits can impede treatment and may result in invasive approaches to care. The current study evaluated the efficacy of graduated exposure with and without extinction to decrease disruption during dental treatment for 4 young men with autism spectrum disorder (ASD). Modified functional analyses confirmed that disruption was maintained by escape from dental demands for all four young men. Initial treatment consisted of graduated exposure, whereby exam steps were initially removed and then gradually reintroduced as disruption remained low; throughout this phase, disruption resulted in a break from the exam. During the subsequent treatment phase, graduated exposure procedures continued and extinction for disruption was added. Graduated exposure alone did not result in sufficient treatment effects; however, the addition of extinction resulted in greater reductions in disruption and increases in exam completion for all 4 young men, and treatment effects generalized to a dental clinic setting.

Single-Cell Encapsulation via Click-Chemistry Alters Production of Paracrine Factors from Neural Progenitor Cells.

Extracellular matrix (ECM) properties affect multiple cellular processes such as cell survival, proliferation, and protein synthesis. Thus, a polymeric-cell delivery system with the ability to manipulate the extracellular environment can act as a fundamental regulator of cell function. Given the promise of stem cell therapeutics, a method to uniformly enhance stem cell function, in particular trophic factor release, can prove transformative in improving efficacy and increasing feasibility by reducing the total number of cells required. Herein, a click-chemistry powered 3D, single-cell encapsulation method aimed at synthesizing a polymeric coating with the optimal thickness around neural progenitor cells is introduced. Polymer encapsulation of neural stem cells significantly increases the release of neurotrophic factors such as VEGF and CNTF. Cell encapsulation with a soft extracellular polymer upregulates the ADCY8-cAMP pathway, suggesting a mechanism for the increase in paracrine factors. Hence, the described single-cell encapsulation technique can emerge as a translatable, nonviral cell modulation method and has the potential to improve stem cells' therapeutic effect.

Author Correction: Morphing electronics enable neuromodulation in growing tissue.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Morphing electronics enable neuromodulation in growing tissue.

Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases1-3. However, their fixed dimensions cannot accommodate rapid tissue growth4,5 and may impair development6. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications6-8. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.

Age-Related Outcomes in Total Ankle Arthroplasty: An Analysis of 112 Patients.

Traditionally, total ankle replacement has been reserved for elderly patients with low physical demands. With nearly 80% of end-stage ankle arthritis being secondary to prior trauma, patients may require a replacement at a much younger rate than primary hip and knee arthritis. Historical accounts of implant failure and high revision rates in younger patients have been reported in the literature. With increasing technology and surgeon experience, implants are being used in younger patients with significantly fewer complications than early reports. In this retrospective review, we evaluated the patient-reported outcome measures and implant complications in three age subsets in arthroplasty patients; Group 1: <55 years-old, Group 2: 55-70 years-old, and Group 3: >70 years-old. In our study, mean postoperative American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scores were 75.5 for group 1, 79.7 for group 2, and 86.9 for group 3, which improved from preoperative scores of 50, 52.4, and 53.8, respectively. Mean postoperative Foot Function Index (FFI) scores were 10 for group 1, 23.9 for group 2, and 12.3 for group 3, which improved from 59.4, 62.8, and 47.6 preoperatively, respectively. The overall complication rate was found to be 11.2%. The complication rate for group 1 was 18%, the complication rate for group 2 was 11.6%, and the complication rate was 9.4% for group 3. The differences in patient AOFAS hindfoot, FFI scores, and complication rates between the groups were not found to be statistically significant. Our results show that patients younger than age 55 years have similar complication rates and reported satisfaction scores to patients 55 years of age and older.

The Effect of Tobacco Use on Incision Healing in Total Ankle Arthroplasty: A Review of 114 Patients.

The purpose of this study was to compare wound complication rates after total ankle replacement in 3 groups of patients based on tobacco status. The total cohort was divided into 3 groups based on tobacco history. Group 1 included patients who were actively tobacco users. Group 2 included patients with a history of tobacco user. Group 3 served as the control group and included patients who had never used tobacco. Available charts were reviewed for patients who underwent primary total ankle arthroplasty by 1 surgeon. Patient demographics, tobacco history, and postoperative wound complications were recorded. A total of 114 patients with tobacco history were available for follow-up and were included in this study, which ranged from March 2012 to July 2017. Group 1 included 11 active smokers. Group 2 included 38 former smokers, and group 3 had a total of 65 never smokers included. The average follow-up was 28 months for group 1 (range 10-55 months), 34.1 months for group 2 (range 12-60 months), and 32.8 months for group 3 (range 11-60 months). The wound complication rate was noted to be statistically significant when comparing active smokers to never smokers using Fisher's exact test (P = .0223). When comparing former smokers with never smokers, the difference in wound complication rate did not reach statistical significance (P = 0.7631). All patients underwent at least 1 concomitant procedure at the time of initial ankle replacement. Our findings show that total ankle replacement wound healing complication rates are significantly higher in active tobacco users. There was no significant difference in wound healing complications when comparing former tobacco users versus never tobacco users. Levels of Evidence: Level III: Retrospective comparative study.

Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds.

Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.

Effects of decreasing intersession interval duration on graduated exposure treatment during simulated routine dental care.

Reports suggest that individuals with developmental disabilities often engage in behavior during dental visits that precludes regular dental care. Graduated exposure therapies are an effective treatment for avoidant behavior in people with developmental delays, and some studies show that the duration of the intersession interval (ISI) can impact the effectiveness of graduated exposure treatments for typically developing individuals. The current study examined the effects of decreasing ISI on outcomes of a graduated exposure treatment during simulated routine dental care for 3 individuals diagnosed with autism. Treatment consisted of graduated exposure and extinction for disruptive behavior. Initially, sessions were conducted once per week. In subsequent conditions, treatment sessions were conducted 3-5 times per week. A nonconcurrent multiple baseline across subjects design was used to demonstrate experimental control. Results suggest that decreasing ISI durations can produce improved treatment outcomes.

Intraoperative Reduction Techniques for Surgical Management of Displaced Intra-Articular Calcaneal Fractures.

Fractures of the calcaneus are detrimental injuries, often caused by high-energy trauma. To best restore the functionality of a limb and allow normal ambulation, it is recommended to repair displaced intra-articular calcaneus fractures surgically. This article presents several methods of reduction and repair of the calcaneus. Traditionally, calcaneal fractures have been repaired through a lateral extensile incision that has been shown to have a high percentage of wound healing complications. In recent times, there has been a shift toward minimally invasive and sinus tarsi incisional approaches in the repair of calcaneus fractures.

Teaching Helping Babies Breathe via Telehealth: A New Application in Rural Guatemala.

BACKGROUND: Helping Babies Breathe (HBB) is a neonatal resuscitation curriculum that teaches life-saving interventions utilized in the first minutes after birth, reducing morbidity and mortality. Traditionally, it requires in-person facilitators for didactic and hands-on training. OBJECTIVES: The aim of this study was to offer HBB to nurses and nursing students in Guatemala, with the lead facilitator presenting concepts via telehealth and in-person facilitators providing hands-on demonstration. METHODS: Learners completed pre- and post-tests that included the standard HBB knowledge check, as well as an assessment of the course teaching model. Learners also completed the standard Objective Structured Clinical Evaluations (OSCEs). RESULTS: Eighteen learners were included in the analysis. All but one learner (94%) passed the course, and the average percent improvement from the pre- to post-test was 12%. All learners achieved passing scores on the OSCEs. Learners responded positively to questions regarding the technology, connection with the instructor, and ability to ask questions. Ninety-four percent of the learners agreed with the statement "this lecture was as good via telehealth as in person." A cost analysis demonstrated approximately USD 3,979.00 in savings using telehealth compared to a standard in-person course. CONCLUSIONS: The telehealth model was successful in delivering course material to the learners and was well received. This model represents a cost-effective way to improve access to HBB. This study may not be generalizable to other populations, and the ability to use telehealth requires reliable internet connectivity, which may not be available in all settings. Further study and expansion of this pilot are needed to assess success in other settings.

The Relationship Between Polyethylene Insert Size and Complications in Total Ankle Replacement.

The purpose of this study was to compare complication rates after total ankle replacement in 2 groups of patients based on polyethylene insert size. The total cohort was divided into 2 groups based on insert size. Group 1 included patients with polyethylene insert size less than 10 mm in thickness. Group 2 included patients with polyethylene insert sizes 10 mm and larger. Available charts were reviewed for patients who underwent primary total ankle arthroplasty by one surgeon. Patient demographics, polyethylene insert size, implant used, concomitant procedures, postoperative complications, and patient-reported outcome scores were recorded. One hundred patients were available for follow-up and were included in this study, which ranged from March 2012 to July 2017. The average follow-up was 31.3 months (range = 10-60 months). Forty-eight females and 52 males were included in this study. There were a total of 63 patients in group 1 and 47 patients in group 2. The total complication rate for patients in group 1 was 11.1% (7/63), and in group 2 it was 16.2% (6/32). There was no statistical significance in complication rates when comparing the 2 groups (P = 0.5427). All patients underwent at least one concomitant procedure at the time of initial ankle replacement. Our findings show that total ankle replacement complication rates are equal when comparing large polyethylene inserts commonly utilized to correct deformities, versus small polyethylene inserts commonly utilized in primary resurfacing. Levels of Evidence: Level IV, Retrospective comparative study.