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Abstract Background Leprosy (Hansen’s disease) is an infectious disease most common in resource-limited countries caused by the acid-fast bacilli Mycobacterium leprae and Mycobacterium lepromatosis that frequently affects the skin and peripheral nerves. Prompt diagnosis and treatment with multidrug therapy is crucial to reduce disease transmission and sequelae, which include nerve function impairment, ocular injury, and stigmatizing physical deformities. Traditional treatment of multibacillary leprosy consists of 12–24 months of multidrug therapy with dapsone, rifampin, and clofazimine. However, this regimen is associated with high pill burden and side effects that limit adherence. Case presentation We report a case of multibacillary leprosy in a previously healthy 30-year-old Hispanic man who recently immigrated to the USA from South America and presented with progressive nodular skin lesions on his face and extremities. He was treated with a monthly regimen of rifampin, moxifloxacin, and minocycline. At follow-up there was significant improvement of his cutaneous lesions without signs of reversal reaction or erythema nodosum leprosum. Conclusions This case report adds to the growing repertoire of literature supporting the use of rifampin, moxifloxacin, and minocycline. Further studies are needed to assess the efficacy of this antimycobacterial regimen and monitor rates of relapse and delayed immunologic reactions, which may occur 5–10 years after completion of treatment.

Abstract Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose–response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity.

La rehabilitación oncológica ha pasado de ser un aspecto secundario en el cuidado de los pacientes con cáncer a convertirse en un componente esencial de la atención integral. Inicialmente, el enfoque se centró en la prevención, el diagnóstico y el tratamiento de esta población, dejando de lado las consecuencias funcionales y psicosociales que causaba la enfermedad. Sin embargo, pioneros como Raven, Dietz y Rusk evidenciaron la necesidad de abordar estas secuelas, impulsando modelos multidisciplinarios con intervenciones físicas, cognitivas y emocionales. En Colombia, el Instituto Nacional de Cancerología ha liderado esfuerzos en el manejo del cáncer durante más de 85 años, integrando especialidades, tecnologías avanzadas y formación académica, situándose como referente regional. En el marco de estos esfuerzos, en 1968 se creó el servicio de rehabilitación oncológica. El aumento en las tasas de supervivencia de los pacientes oncológicos a nivel internacional alentó la implementación de programas que incorporan la rehabilitación oncológica de forma temprana. Aún se evidencia la necesidad de más profesionales especializados y mayor difusión de la importancia de la rehabilitación y de políticas que la respalden con el fin de garantizar una atención oncológica integral que incluya no solo la supervivencia, sino también la calidad de vida y la funcionalidad de los pacientes.

Objective. To determine the effect on voice parameters in pupils and their teacher of a three-week Workplace Vocal Health Promotion Program (WVHPP) in a school setting. Methods. Longitudinal study with a design phase and a pilot phase. Voice recordings of connected speech were used to collect information on voice functioning before and after the implementation of the program. The workplace vocal health promotion program was implemented with two purposes: (1) to reduce noisy conditions inside the classrooms that may cause loud voice production, which has been found associated with voice disorders among teachers and students and (2) to increase awareness about the relationship between noise and voice inside the classrooms. Results. The WVHPP was found to be statistically associated with a decrease in the fundamental frequency, standard deviation of the fundamental frequency, sound pressure levels, and SPL standard deviation among both pupils and their teacher. However, there was no statistically significant effect on cepstral peak prominence smoothed. Conclusion. The three-week WVHPP was found to have a significant impact on several acoustic parameters, such as the fundamental frequency and sound pressure levels. These findings highlight the potential of the WVHPP as an effective intervention for improving the vocal health of both teachers and students. However, the lack of a significant effect on cepstral peak prominence smoothed suggests that further research is needed to fully understand the impact of the WVHPP on voice quality.

Abstract The continuous growth of annual production and consumption of polyethylene terephthalate (PET) is coined with increasing waste that leaks into the environment, landfills and oceans as microplastics and nano plastics fragments. Upcycling the recycled PET to make a feedstock for the fast-growing material-extrusion additive manufacturing (MEX-AM) technology can contribute to the solution and supports the concept of sustainable materials. In this work, extrudable filaments comprising recycled polyethylene terephthalate (rPET) with low-cost additives, such as pyromellitic dianhydride (PMDA) as a chain extender, styrene-ethylene-butylene-styrene terpolymer functionalized with maleic anhydride (SEBS-g-MA), a thermal modifier and toughening agent, ethylene-ethyl acrylate-glycidyl methacrylate terpolymer (E-EA-GMA), a functional reactive elastomeric impact modifier and ethylene-ethyl-acrylate (EEA), a non-reactive elastomeric impact modifier, have been fabricated using the twin-screw extruder. The optimum extrusion process parameters for producing uniform filaments of different rPET compounded formulations have been identified, this includes the extrusion die temperature of 280 °C and the screw speed of 150 ± 3 rpm. The compounded filaments are then printed into standard ASTM test specimens for thermal characterization and mechanical characterization, including glass transition and melting temperatures, crystallinity and crystallization temperature, tensile strength, tensile modulus, ductility, flexural strength, and Izod impact energy. Furthermore, the melt flow index for the filaments was measured. More significantly, the experimental data showed that compounding rPET with such additives in the reactive twin-screw extrusion process results in uniform filaments that display advantageous thermal and mechanical properties and can be used as a feedstock in the MEX-AM technology. This study suggests that compounding the recycled PET pellets with low-cost additives while extruding them into filaments for MEX-AM offers excellent potential to make high-value-added customized products from a sustainable polymer feedstock, such as prototyping, tooling, testing components or end-use internal components for small machines and cars.

COVID-19 vaccinations are widely available across the United States (U.S.), yet little is known about the spatial clustering of COVID-19 vaccinations. This study aimed to test for geospatial clustering of COVID-19 vaccine rates among adolescents aged 12–17 across the U.S. counties and to compare these clustering patterns by sociodemographic characteristics.County-level data on COVID-19 vaccinations and sociodemographic characteristics were obtained from the COVID-19 Community Profile Report up to April 14, 2022. A total of 3,108 counties were included in the analysis. Global Moran’s I statistic and Anselin Local Moran’s analysis were used, and clustering patterns were compared to sociodemographic variables using t-tests. Counties with low COVID-19 vaccinated clusters were more likely, when compared to unclustered counties, to have higher numbers of individuals in poverty and uninsured individuals, and higher values of Social Vulnerability Index (SVI) and COVID-19 Community Vulnerability Index (CCVI). While high COVID-19 vaccinated clusters, compared to neighboring counties, had lower numbers of Black population, individuals in poverty, and uninsured individuals, and lower values of SVI and CCVI, but a higher number of Hispanic population. This study emphasizes the importance of addressing systemic barriers, such as poverty and lack of health insurance, which were found to be associated with low COVID-19 vaccination coverage.

Objective. This study examines factors predicting self-reported voice symptoms in call center workers. Methods. Multivariate analysis and predictive modeling assess personal, work-related, acoustic, and behavioral factors. Generalized Linear Models (GLMs) and Receiver Operating Characteristic (ROC) curves are employed. Results. Age and sleep patterns impacted voice quality and effort, while workplace factors influenced symptom perception. Unhealthy vocal behaviors related to tense voice and increased effort, while hydration was protective. Voice acoustics showed diagnostic potential, supported by ROC data. These findings emphasize voice symptom complexity in call center professionals, necessitating comprehensive assessment. Limitations. This study recognizes its limitations, including a moderate-sized convenience sample and reliance on PROM metrics. Future research should incorporate more objective measures in addition to self-reports and acoustic analysis. Value. This research provides novel insights into the interplay of personal, occupational, and voice-related factors in developing voice symptoms among call center workers. Predictive modeling enhances risk assessment and understanding of individual susceptibility to voice disorders. Conclusion. Results show associations between various factors and self-reported voice symptoms. Protective factors include sleeping more than six hours and consistent hydration, whereas risk factors include working conditions, such as location and behaviors like smoking. Diagnostic models indicate good accuracy for some voice symptom PROMs, emphasizing the need for comprehensive models considering work factors, vocal behaviors, and acoustic parameters to understand voice issues complexity.

El presente documento resume los principales aportes del conversatorio titulado “Trabajo interdisciplinario en las profesiones de la voz humana: retos, límites y proyecciones”, organizado por Vocology Center el 18 de julio de 2023, que reunió a líderes y representantes de diversas agremiaciones relacionadas con la voz humana, incluyendo profesionales del ámbito clínico, artístico, rehabilitación vocal, voz ocupacional, pedagogía vocal y otras disciplinas afines. El propósito de este conversatorio fue promover un debate crítico sobre la naturaleza del trabajo interdisciplinario en el estudio de la voz humana. Se exploraron los desafíos que surgen al configurar equipos de trabajo que incluyan profesionales con diferentes enfoques y experticias en el abordaje de la voz, así como los límites inherentes a los diversos roles y funciones desempeñados por los profesionales especializados en este campo, junto con las cuestiones éticas emergentes en este proceso. Con un enfoque encaminado a fortalecer alianzas interdisciplinarias, el evento se centró en la búsqueda de una comunicación y colaboración más efectiva. Este documento marca un avance significativo en la comprensión y colaboración interdisciplinar en el cuidado de la voz humana.

In face-to-face household surveys, field interviewers are sometimes asked to make notes of characteristics of the dwelling unit on the sampled address as well as its surroundings before making contact with a household member living at the sample address. Field interviewer observations of this kind are used to improve efficiency of field data collection and to be used as nonresponse adjustment. However, field interviewer observations can be expensive and the quality of observations needs to be improved. Recently, survey organizations start to utilize Google Street View to conduct virtual observations of the dwelling unit and the neighborhood. This paper reports a feasibility study that evaluates the feasibility of using virtual observations, assesses its agreement with field interviewer observation results, and examine whether virtual observations correlate with survey response status and survey estimates. We found moderate to high agreements between virtual and interviewer observation results. We also found that some observation results are significantly related to response status and survey estimates. However, virtual observations using GSV have coverage issues, which could limit their potential use.

This study investigates the frequency of a clinically reported variant in PMS2, NM_000535.7:c.2523G>A p.(W841∗), from next-generation sequencing studies in 2 racially diverse cohorts. We identified clinical reports of the PMS2 c.2523G>A p.(W841∗) variant in the National Precision Oncology Program’s somatic testing database (n = 25,168). We determined frequency of the variant in germline exome sequencing from the Penn Medicine BioBank (n = 44,256) and in gnomAD. The PMS2 c.2523G>A p.(W841∗) was identified as a homozygous variant on tumor testing in an adult patient of self-identified Black race/ethnicity with no evidence of constitutional mismatch repair deficiency. The variant was clinically reported on 35 total tumor and liquid biopsy tests (0.1%), and all individuals with the variant were of self-identified Black race/ethnicity (0.6% of n = 5787). In individuals of African genetic ancestry (AFR), the variant's germline frequency was reported to be 0.2% and 1.3% in the Penn Medicine BioBank (PMBB) and gnomAD, respectively. The variant cannot be found in any individuals of European genetic ancestry (EUR) from either of the databases. The variant is found in a region of PMS2 with 100% homology to the PMS2CL pseudogene. PMS2 c.2523G>A p.(W841∗), when identified, is typically an African-ancestry-specific PMS2CL pseudogene variant, which should be recognized to prevent misdiagnosis of Lynch syndrome in Blacks.

The field of voice disorders lost a true pioneer with the passing of Dr. Cristina Jackson-Menaldi (June 21, 1950 - November 20, 2020). A renowned voice pathologist and singing voice specialist, Dr. Jackson-Menaldi made significant contributions to our understanding and treatment of voice disorders. She was also a passionate advocate for voice education and disorder prevention.

Objetivo. Identificar factores asociados al presentismo laboral y la calidad de vida relacionada con la voz en docentes universitarios colombianos con clases virtuales en tiempos de COVID-19. Metodología. Estudio transversal en el que veintinueve docentes de una universidad pública de Colombia participaron. Se utilizó un cuestionario en línea en la plataforma Google Forms, en el que se incluyeron preguntas sobre sintomatología vocal, calidad de vida asociada a la voz y al presentismo laboral asociado con sintomatología vocal. El análisis estadístico se realizó utilizando el software SPSS 25 (IBM Corporation). Resultados. El análisis multivariado de los factores asociados con el presentismo mostró que cuatro variables aumentaban los días de presentimos laboral, siendo el reporte de síntomas de voz en el mes previo a la recolección de datos la variable que aumentó en mayor proporción, seguido de estado civil soltero, número de estudiantes y el factor 2 del IFV. Respecto a los factores asociados de la calidad de vida relacionada con la voz, el análisis multivariado mostró que el reporte de incomodidad física asociada con la fonación (Factor 2 del IFV) fue la única variable que permaneció estadísticamente significativa. Conclusión. La fatiga vocal y la incomodidad física asociada con la fonación, así como el estado civil, están asociados con el presentismo vocal y la calidad de vida relacionada con la voz. Estos resultados resaltan las implicaciones de la sintomatología vocal en la salud, el bienestar y la economía de los docentes y las instituciones educativas, información que es importante cuando se requiere priorizar medidas preventivas y estrategias de intervención para los síntomas de voz y la fatiga vocal en docentes.

Introducción. La malaria, o paludismo, es una enfermedad de gran impacto en la población colombiana, que debe ser abordada desde el punto de vista del trabajo en equipo de instituciones para el intercambio de conocimiento. Objetivo. Analizar las interacciones de la Red de Gestión del Conocimiento, Investigación e Innovación en Malaria de Colombia. Materiales y métodos. Se hizo un análisis de redes sociales que permitió identificar la proximidad entre los actores y el grado de conocimiento entre ellos; se observaron indicadores de densidad, diámetro, distancia media y centralidad de grado. El corpus documental para el estudio estuvo constituido por 193 documentos técnicos publicados entre el 2016 y el 2021, que fueron analizados empleando técnicas de procesamiento de texto mediante el lenguaje de programación R. La categorización de la red se realizó a partir de cinco variables: atención integral a pacientes, diagnóstico, epidemiología y sistemas de análisis de información en salud, política pública, y promoción y prevención. Resultados. El análisis de las interacciones indicó que la red la conformaban 99 actores, de los cuales 97 (98 %), mostraron más interés en la producción de conocimientos en epidemiología y sistemas de análisis de información en salud, seguido de la categoría de atención integral a pacientes con 79 (80 %). El 54 % de los actores llevó a cabo estudios de promoción y prevención, siendo esta la categoría de menor abordaje. Conclusiones. Este estudio contribuye al fortalecimiento de estrategias clave en la divulgación del conocimiento sobre la malaria en Colombia.

Rader et al. model spatial accessibility to COVID-19 vaccines in the US, identifying vaccine deserts where access was insufficient during the first phase of the rollout. Rural areas and medically vulnerable populations are found to have poorer access to vaccines, as are areas with higher proportions of Black, Hispanic and older residents.

Active duty service members and their families have unique behavioral health care service needs. The purpose of this study is to determine geographical access to specialized behavioral health programs tailored to active duty U.S. service members and military families from military installations. This study generated network distance measures between active duty military installations and licensed substance use disorder (SUD) treatment facilities and mental health treatment facilities for 2015–2018 using data from national surveys administered by the Substance Abuse and Mental Health Services Administration and coordinates for active duty military installations from the Defense Installation Spatial Data Infrastructure Program. Using regression analysis, we calculated the share of installations that are at-risk of being remote from behavioral healthcare services. Separately, we calculated the share of treatment facilities accepting military insurance that offer specialized programs for active duty service members and/or military families within a 30-minute drive to an installation. Three out of 10 installations were at-risk of being remote from a behavioral health treatment facility. About 25 percent of behavioral health treatment facilities accepting military insurance within a 30-minute drive to an installation offered a specialized treatment program for active duty military or military families. Lack of a specialized treatment programs could suggest facilities may not be equipped to manage stressors unique to being in the military, and as a consequence, could adversely impact the health and well-being of this population. Further research is necessary to understand what specialized treatment programs for military populations entail.

Abstract Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to heterogeneity in culture conditions. We investigated the effect of passage number on iPSC differentiation to optimize the generation of sensory neurons (iPSC-dSNs). Three iPSC lines reprogrammed from the peripheral blood of three donors were differentiated into iPSC-dSNs at passage numbers within each of the following ranges: low (5–10), intermediate (20–26), and high (30–38). Morphology and pluripotency of the parent iPSCs were assessed prior to differentiation. iPSC-dSNs were evaluated based on electrophysiological properties and expression of key neuronal markers. All iPSC lines displayed similar morphology and were similarly pluripotent across passage numbers. However, the expression levels of neuronal markers and sodium channel function analyses indicated that iPSC-dSNs differentiated from low passage numbers better recapitulated the sensory neuron phenotype than those differentiated from intermediate or high passage numbers. Our results demonstrate that lower passage numbers may be better suited for differentiation into peripheral sensory neurons.

988, a national mental health emergency hotline number, went live throughout the United States in July 2022. 988 connects callers to the 988 Crisis & Suicide Lifeline, previously known as the National Suicide Prevention Lifeline. The transition to the three-digit number aimed to respond to a growing national mental health crisis and to expand access to crisis care. We examined preparedness throughout the U.S. for the transition to 988. In February and March 2022, we administered a national survey of state, regional, and county behavioral health program directors. Respondents (n = 180) represented jurisdictional coverage of 120 million Americans. We found that communities throughout the U.S. appeared ill-prepared for rollout of 988. Fewer than half of respondents reported their jurisdictions were ‘somewhat’ or ‘very’ prepared for 988 in terms of financing (29%), staffing (41%), infrastructure (41%), or service coordination (47%). Counties with higher representation of Hispanic/Latinx individuals were less likely to report being prepared for 988 in terms of staffing (OR: 0.62, 95 %CI: 0.45, 0.86) and infrastructure (OR: 0.68, 95 %CI: 0.48, 0.98). In terms of existing services, sixty percent of respondents reported a shortage of crisis beds and fewer than half reported availability of short-term crisis stabilization programs in their jurisdictions. Our study highlights components of local, regional, and state behavioral health systems in the U.S. that require greater investments to support 988 and mental health crisis care.

Abstract Background The in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation. Methods 13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated. Results TPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p 0.08) or average hyperemic response (p > 0.09). Conclusions Although women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.

Introduction. Due to the COVID-19 pandemic, teaching conditions changed around the world from in-person classes to online classes, which also determined changes on teachers’ working conditions. Method: Exploratory cross-sectional study with the aim of determining the association between two voice symptoms (vocal fatigue and throat pain) with home working conditions during online classes in times of COVID-19 pandemic. Professors answered an online survey including 27 questions about four components: sociodemographic factors, characteristics of home working, quarantine characteristics, and health conditions (including voice functioning). Results: 177 college professors from Argentina, Colombia, and Chile participated in this study. First, incidence of vocal fatigue, during online classes in times of COVID-19 pandemic, represented around 50%. Although throat pain had a smaller incidence, it was also important (35%). Second, days in quarantine, number of classes per week, people living with during quarantine, and history of vocal fatigue before quarantine were important associated factors of vocal fatigue. Third, important associated factors of throat pain were number of classes per week, level of stress, years of experience, and history of throat pain before quarantine. Conclusion: Similar to pre-COVID-19, vocal fatigue and throat pain were frequently reported voice symptoms among college professors. Associated factors of these symptoms included years of experience, number of classes per week, stress, people living with during quarantine due to COVID-19, and history of voice symptoms. Workplace Health Promotion programs should include activities that facilitate a healthy occupational voice use during and post-COVID-19 pandemic, considering the implications of online teaching on teachers’ health and safety.

Objective. To estimate the productivity reduction costs associated to self-reported voice symptoms, low sleep quality, and high stress levels among college professors during homeworking in times of COVID-19 pandemic. Methods. This cross-sectional study included fifty-eight college professors who reported their reduction in productivity at work due to self-perceived stress levels, sleep quality, and voice symptoms. Results. High stress levels were reported by 24% of the participants, whereas 19% reported voice symptoms, and 3% low sleep quality. Costs associated with the three conditions were calculated for twenty-nine subjects. Productivity costs associated with high stress levels were higher (COP$32.345.925) than those for voice symptoms (COP$1.872.703) and low sleep quality (COP$319.733). Conclusion: Productivity reduction costs were higher for professors who reported high levels of stress followed by participants with self-reported voice symptoms and low sleep quality, which highlight the importance of prioritizing activities to reduce stress levels and voice symptoms in workplace health promotion programs implemented in educational settings.

Abstract Calves with Bovine Respiratory Disease (BRD) have different feeding behavior and activity levels prior to BRD diagnosis when compared to healthy calves, but it is unknown if calves who relapse from their initial BRD diagnosis are behaviorally different from calves who recover. Using precision technologies, we aimed to identify associations of feeding behavior and activity with recovery status in dairy calves (recovered or relapsed) over the 10 days after first antimicrobial treatment for BRD. Dairy calves were health scored daily for a BRD bout (using a standard respiratory scoring system and lung ultrasonography) and received antimicrobial therapy (enrofloxacin) on day 0 of initial BRD diagnosis; 10–14 days later, recovery status was scored as either recovered or relapsed (n = 19 each). Feeding behaviors and activity were monitored using automated feeders and pedometers. Over the 10 days post-treatment, recovered calves showed improvements in starter intake and were generally more active, while relapsed calves showed sickness behaviors, including depressed feed intake, and longer lying times. These results suggest there is a new potential for precision technology devices on farms in evaluating recovery status of dairy calves that are recently treated for BRD; there is opportunity to automatically identify relapsing calves before re-emergence of clinical disease.

Introducción: La tuberculosis es una enfermedad infectocontagiosa de fácil trasmisión. Para su control, los conocimientos, actitudes y prácticas adecuadas son indispensables, así como los factores relevantes para la adherencia al tratamiento. Objetivo: Caracterizar las definiciones o los conceptos de las dimensiones de conocimientos, actitudes y prácticas en tuberculosis reportados en la literatura durante los últimos diez años. Materiales y métodos: Se realizó una revisión sistemática de la literatura bajo la metodología “Preferred Reporting Items for Systematic Reviews and Meta-Analyses”. Inicialmente, se encontraron 1.720 posibles publicaciones, de las cuales, luego de la aplicación de los criterios de exclusión, quedaron 34 para ser incluidas en el análisis de esta revisión. Resultados: La mayoría de los estudios fueron publicados en el año 2018 y predominaron las publicaciones en el continente africano. La caracterización de las dimensiones se relaciona así: los conocimientos se definen como características de la enfermedad, las actitudes se relacionan con el estigma social hacia el paciente y las prácticas corresponden con la búsqueda de atención médica por parte del paciente. Conclusión: Se identificó la escasez de producción científica en donde se especifiquen los conceptos de las dimensiones de conocimientos, actitudes y prácticas, que a su vez permitan el desarrollo de investigaciones de alto rigor y alcance metodológico, ya que las publicaciones realizadas e incluidas para este estudio tuvieron una evaluación de baja calidad.

Controlled protein synthesis is required to regulate gene expression and is often carried out in a cell type-specific manner. Protein synthesis is commonly measured by labeling the nascent proteome with amino acid analogs or isotope-containing amino acids. These methods have been difficult to implement in vivo as they require lengthy amino acid replacement procedures. O-propargyl-puromycin (OPP) is a puromycin analog that incorporates into nascent polypeptide chains. Through its terminal alkyne, OPP can be conjugated to a fluorophore-azide for directly visualizing nascent protein synthesis, or to a biotin-azide for capture and identification of newly-synthesized proteins. To achieve cell type-specific OPP incorporation, we developed phenylacetyl-OPP (PhAc-OPP), a puromycin analog harboring an enzyme-labile blocking group that can be removed by penicillin G acylase (PGA). Here, we show that cell type-specific PGA expression in Drosophila can be used to achieve OPP labeling of newly-synthesized proteins in targeted cell populations within the brain. Following a brief 2 hr incubation of intact brains with PhAc-OPP, we observe robust imaging and affinity purification of OPP-labeled nascent proteins in PGA-targeted cell populations. We apply this method to show a pronounced age-related decline in neuronal protein synthesis in the fly brain, demonstrating the capability of PhAc-OPP to quantitatively capture in vivo protein synthesis states. This method, which we call POPPi (PGA-dependent OPP incorporation), should be applicable for rapidly visualizing protein synthesis and identifying nascent proteins synthesized under diverse physiological and pathological conditions with cellular specificity in vivo.

Nonbacterial thrombotic endocarditis (NBTE) is a pathologic state associated with autoimmune diseases and malignancy in which platelet thrombi are deposited on the heart valves in the absence of a bloodstream infection. NBTE is a diagnosis of exclusion that requires a high degree of clinical suspicion after infective endocarditis etiologies have been ruled out. The treatment of NBTE consists of systemic anticoagulation, with direct oral anticoagulants and surgery not having a clear role. The following case reviews a patient’s journey to the diagnosis of tricuspid valve nonbacterial thrombotic endocarditis in the setting of recently diagnosed metastatic lung cancer. This case adds to the growing literature on the diagnostic approach to NBTE.

Objetivo. Describir los resultados de una estrategia de acompañamiento virtual y presencial, con base en el cuidado centrado en la persona durante la atención a pacientes hospitalizados por sospecha o confirmación de enfermedad por el nuevo coronavirus 2019 (COVID-19, por su sigla en inglés). Método. Estudio observacional descriptivo retrospectivo realizado en cinco instituciones de salud de la red de clínica Colsanitas que implementaron una estrategia de acompañamiento con siete modalidades: información virtual, dispositivos móviles personales, visitas virtuales, contactos con otros medios, acompañante permanente, visita presencial y contacto compasivo. Se utilizó estadística descriptiva para el análisis de los datos. Resultados. La estrategia de acompañamiento se aplicó a 871 pacientes con estancia hospitalaria de 1 a 90 días, 70% fueron positivos para COVID-19; en la modalidad de información virtual, se contactaron a familias de 764 pacientes realizando 3984 llamadas; en promedio se realizaron 71 visitas virtuales al día; se recibieron 428 cartas, mensajes de voz y videos, entre otros; 114 pacientes tuvieron un acompañante permanente; 154 pacientes tuvieron visita presencial; y 20 familias realizaron visita presencial póstuma al paciente. Conclusión. Los resultados de la estrategia de acompañamiento virtual y presencial con enfoque centrado en la persona mostraron que la participación de las familias es importante en el cuidado del paciente y mejora la comunicación e interacción entre los pacientes, las familias y el equipo de salud.

Objectives: 1. define the occurrence of work-related hearing problems and voice disorders among teachers that have contacted the Colombian National Board of Disability Assessment (NBDA) for follow-up; 2. identify individual associated factors of hearing problems and voice disorders among teachers; 3. assess the limitations and restrictions due to hearing problems and voice disorders among these participants. Methods: Retrospective study. The National Database of the Colombian NBDA was reviewed. Information on distributions of occupation, individual characteristics, and diagnosis code (ICD-10) was analyzed. Results: Communication disorders among teachers that have contacted the Colombian NBDA for follow-up included voice disorders, with a prevalence of 51%, and hearing problems, with a prevalence of 7%. Female teachers who have contacted the Colombian NBDA for follow-up were 4 times more likely to be identified as having voice disorders compared with their male colleagues. Conclusions: While teachers that have contacted the Colombian NBDA for follow-up have a high occurrence of voice disorders, hearing problems are more likely to be stated as a debilitating condition. One possible explanation is that teachers who contacted the Colombian NBDA for follow-up continued working even when many voice symptoms were evident, while hearing problems would prevent a teacher from interacting with students, thereby affecting the teaching-learning process sooner. Nevertheless, with both voice and hearing problems, work performance and social interaction is affected, and, therefore, quality of life is reduced.

Abstract Objective To evaluate the functional outcomes of patients diagnosed with femoroacetabular impingement (FAI) older than 60 years, compared with those of patients of age 40 years or younger. Methods This was a retrospective review of patients with FAI who underwent hip arthroscopy between 2010 and 2015. The patients were adults aged over 60 years with Tönnis ≤ 1 matched in a 1:1 ratio with adults aged 40 years or younger, according to the type of deformity (cam, pincer, or mixed), sex, and the date when the surgery was performed. Results Thirty-four patients were included in each group. The mean age was 30.6 ± 6.9 years and 65.6 ± 4.6 years in the control and case groups, respectively. There were no significant differences between the groups at 1-year follow-up (p > 0.05). In the group with older patients (case group), we observed a change in the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from 46.3 to 22.0 in the 1st postoperative year, while the control cases improved in the WOMAC score from 38.1 to 7.2 in relation to the preoperative stage. Conclusion In the group of patients ≤ 40 years old, a considerable change was observed in the WOMAC score without a statistical significance compared with the > 60 years group. This observation suggests that hip arthroscopy is beneficial when there is an appropriate selection of patients with FAI, regardless the age of the patient.

Effective conservation actions require effective population monitoring. However, accurately counting animals in the wild to inform conservation decision-making is difficult. Monitoring populations through image sampling has made data collection cheaper, wide-reaching and less intrusive but created a need to process and analyse this data efficiently. Counting animals from such data is challenging, particularly when densely packed in noisy images. Attempting this manually is slow and expensive, while traditional computer vision methods are limited in their generalisability. Deep learning is the state-of-the-art method for many computer vision tasks, but it has yet to be properly explored to count animals. To this end, we employ deep learning, with a density-based regression approach, to count fish in low-resolution sonar images. We introduce a large dataset of sonar videos, deployed to record wild Lebranche mullet schools (Mugil liza), with a subset of 500 labelled images. We utilise abundant unlabelled data in a self-supervised task to improve the supervised counting task. For the first time in this context, by introducing uncertainty quantification, we improve model training and provide an accompanying measure of prediction uncertainty for more informed biological decision-making. Finally, we demonstrate the generalisability of our proposed counting framework through testing it on a recent benchmark dataset of high-resolution annotated underwater images from varying habitats (DeepFish). From experiments on both contrasting datasets, we demonstrate our network outperforms the few other deep learning models implemented for solving this task. By providing an open-source framework along with training data, our study puts forth an efficient deep learning template for crowd counting aquatic animals thereby contributing effective methods to assess natural populations from the ever-increasing visual data.

Introducción: La neuroartropatía es una afección secundaria a enfermedades metabólicas, infecciosas o genéticas. Su localización usual está reportada en el pie, pero puede afectar cualquier articulación, compromete su estado vascular y modifica la condición ósea, genera fracturas, contracturas y luxaciones. Objetivos: Reportar los hallazgos clínicos e imagenológicos de una paciente con neuroartropatía de Charcot por diabetes mellitus, en una localización articular, poco frecuente. Caso Clínico: Paciente femenina de 62 años, procedente del suroccidente colombiano, con antecedentes de diabetes mellitus y complicaciones micro y macrovasculares. Presentó un cuadro clínico de dolor articular en la rodilla derecha, que evolucionó a una imposibilidad para la marcha. En su atención se realizaron diferentes estudios de imagen; se encontró una fractura del cóndilo femoral izquierdo y de los platillos tibiales. Estas características radiológicas típicas, más los cambios clínicos de la articulación, llevaron al diagnóstico de rodilla de Charcot. Se realizaron intervenciones farmacológicas analgésicas, además de inmovilización articular, con adecuada evolución en el seguimiento clínico. Conclusiones: La neuroartropatía con rodilla de Charcot es una afección que debe ser evaluada en todos los pacientes con diabetes mellitus y otras enfermedades, ampliar el panorama de revisión articular a localizaciones menos frecuentes, como la rodilla. Una intervención temprana y multidisciplinaria puede favorecer los desenlaces clínicos positivos.

Introduction: Neuroarthropathy is a condition secondary to metabolic, infectious, or genetic diseases. Its usual localization is reported in the foot, but it can affect any joint, compromising its vascular status and modifying the bone condition generating fractures, contractures, and dislocations. Objectives: To report the clinical and imaging findings of a patient with Charcot neuroarthropathy due to diabetes mellitus in a rare joint location. Clinical Case: A 62-year-old woman from colombian southwestern, with a history of diabetes mellitus, in addition to micro and macrovascular complications. She presented a clinical picture of joint pain in the right knee that evolved to an inability to walk. During her care, different imaging tests were performed, finding a fracture of the left femoral condyle and tibial plateau, these typical radiological characteristics plus the clinical changes of the joint, led to the diagnosis of Charcot's knee. Pharmacological interventions were performed in pain in addition to joint immobilization, with adequate evolution in clinical follow-up. Conclusions: Neuroarthropathy is a condition that should be evaluated in all patients with diabetes mellitus and other conditions, expanding the joint revision panorama to less frequent locations such as the knee; early and multidisciplinary intervention can favor positive clinical outcomes.

Introducción. Clostridium difficile ocasiona infecciones hospitalarias que resultan en altas tasas de morbilidad y mortalidad. La cepa NAP1/027 se ha asociado con una mayor producción de toxinas y con una mayor gravedad, lo que aumenta la carga de la enfermedad. Objetivo. Describir la epidemiología de las infecciones asociadas con C. difficile y las características de la cepa NAP1/027. Materiales y métodos. Se hizo un estudio observacional basado en la revisión de las historias clínicas de los pacientes con muestras de heces positivas para C. difficile identificadas mediante la prueba Xpert™ entre el 2012 y el 2015 en un hospital de alta complejidad. La gravedad de la enfermedad se evaluó con el índice ATLAS. Resultados. Se incluyeron 42 casos de pacientes infectados, 9 de los cuales fueron positivos para la cepa NAP1/027. El uso de antibióticos antes de la infección durante más de siete días fue más frecuente en los casos de pacientes con muestras negativas para NAP1/027. En la mitad de los pacientes, la duración de la diarrea fue mayor de cinco días y no hubo diferencias según el tipo de cepa (p>0,05). Los casos de pacientes positivos para la cepa NAP1/027 se caracterizaron por presentar deposiciones fétidas y sanguinolentas. La gravedad de la infección fue similar entre los grupos. Conclusión. Se comprobó la circulación de la cepa NAP1/027, pero su presencia no supuso diferencias clínicas significativas con respecto a otras cepas, lo cual podría deberse al limitado número de pacientes en este estudio. Sin embargo, su presencia debe alertar a los médicos y a las instituciones de salud, dada su frecuente asociación con la gravedad de la infección y la mortalidad.

We greatly appreciate the comments made by Rojas-Botero et al.1 on our paper entitled “Critical reflections on the Municipal Epidemiological Resilience Index used for public policy decision-making regarding the control of the COVID-19 pandemic in Colombia”.2 We acknowledge that public health, understood as the well-being of the community, should be the focus of all our efforts as health professionals. In this sense, decision-making amid a major emergency, such as the one we are currently experiencing due to the COVID-19 pandemic, requires a balanced and calm judgment that considers both the general context and local specificities, as well as the best available scientific evidence, that is, evidence that not only supports decisions, but also prioritizes benefits over risks.

On June 2, 2021, the Colombian Ministry of Health and Social Protection, through Resolution No. 777, laid down the requirements to resume all restricted economic and social activities. Similarly, said Resolution established the Municipal Epidemiological Resilience Index (IREM by its acronym in Spanish) as a tool to support decision-making regarding this economic reactivation amid the third epidemic peak of COVID-19 in the country. The purpose of this article is to perform a critical analysis of the technical aspects of the IREM and to explore the feasibility of its implementation as a support for the resumption of economic and social activities as proposed in the Resolution. The present critical analysis emphasizes on the lack of a clear definition of epidemiological resilience that is consistent with the scientific literature. Furthermore, the face and content validity of the index, as well as the construct validity of the index and of its dimensions, are called into question and, therefore, the feasibility of using it to determine said resumption.

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.

Aim: the purpose of this study was to translate and adapt the English version of the Vocal Fatigue Index (VFI) into the Spanish language. Methods: the English version of the Vocal Fatigue Index (VFI) was translated into Spanish by two bilingual speech-language pathologists, and then was back-translated into English. The Spanish VFI (o “Índice de Fatiga Vocal”, IFV) was administrated to a pilot group of 10 individuals, which revealed some small typographical and grammatical adjustments to the index. The final updated version was then administrated to 34 subjects (21 with voice disorders, and 13 without voice disorders). Internal consistency and scale reliability were analyzed using Cronbach alpha coefficient. Results: a high Cronbach alpha coefficient for the three factors (0.87) was obtained. The results of the item role in reliability of the Spanish VFI demonstrated that all of them showed a positive role according to this criterion. The results of the ANOVA indicate a statistically significant difference between groups on the three scores of the Spanish translation of the VFI. In comparison to the healthy participants, those with voice disorders obtained statistically significant higher scores for the Spanish VFI subscales. Conclusion: the present study suggests that the Spanish translation of the Vocal Fatigue Index has a good internal consistency and high reliability on each of the three factors. The results suggest that the Spanish VFI can be used reliably to identify persons with vocal fatigue and has good clinical validity.

Introduction Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory musculoskeletal disorder that manifests as peripheral arthritis, dactylitis, enthesitis and spondylitis. PsA results in significant burden that impacts quality of life of patients. We examined the signs, symptoms and impacts reported by patients with PsA, to characterise the patient experience of PsA and develop a conceptual model representing this patient experience.Methods Semi-structured interviews were conducted with patients with PsA recruited through the FORWARD databank. Spontaneous and probed signs, symptoms and impacts of PsA were assessed. Patients rated the disturbance of these concepts on their lives using a scale from 0 (‘does not disturb’) to 10 (‘greatly disturbs’). Signs, symptoms and impacts reported by >80% of patients with a disturbance rating of ≥5 were defined as salient concepts. Recruitment continued until concept saturation was achieved.Results 19 patients with PsA were interviewed. The interviews elicited 42 symptoms of which 8 had not been identified in a previous literature review encompassing 15 relevant articles. The most salient signs and symptoms elicited in the interviews were joint pain, skin symptoms, stiffness, swollen/inflamed joints and fatigue all with moderate to high disturbance ratings (range: 5.5–7.8). The most salient impacts were sleep disturbance, physical disability, effects on daily activities and feelings of frustration with also moderate to high disturbance ratings (range: 6.1–7.4).Conclusions The interviews highlighted the adverse impact PsA has on the patient’s life and may inform on outcome variables or areas suitable to be assessed in PsA studies.

Aging and age-related disease represents a substantial quantity of current natural, social and behavioral science research efforts. Presently, no centralized system exists for tracking aging research projects across numerous research disciplines. The multidisciplinary nature of this research complicates the understanding of underlying project categories, the establishment of project relations, and the development of a unified project classification scheme. We have developed a highly visual database, the International Aging Research Portfolio (IARP), available at AgingPortfolio.org to address this issue. The database integrates information on research grants, peer-reviewed publications, and issued patent applications from multiple sources. Additionally, the database uses flexible project classification mechanisms and tools for analyzing project associations and trends. This system enables scientists to search the centralized project database, to classify and categorize aging projects, and to analyze the funding aspects across multiple research disciplines. The IARP is designed to provide improved allocation and prioritization of scarce research funding, to reduce project overlap and improve scientific collaboration thereby accelerating scientific and medical progress in a rapidly growing area of research. Grant applications often precede publications and some grants do not result in publications, thus, this system provides utility to investigate an earlier and broader view on research activity in many research disciplines. This project is a first attempt to provide a centralized database system for research grants and to categorize aging research projects into multiple subcategories utilizing both advanced machine algorithms and a hierarchical environment for scientific collaboration.

Abstract As part of GAW20, we analyzed the familiality and variability of methylation to identify cytosine-phosphate-guanine (CpG) sites responsive to treatment with fenofibrate. Methylation was measured at approximately 450,000 sites in pedigree members, prior to and after 3 weeks of treatment. Initially, we aimed to identify responsive sites by analyzing the pre- and posttreatment methylation changes within individuals, but these data exhibited a confounding treatment/batch effect. We applied an alternative indirect approach by searching for CpG sites whose methylation levels exhibit a genetic response to the drug. We reasoned that these sites would exhibit highly familial and variable methylation levels posttreatment, but not pretreatment. Using a 0.1% threshold, posttreatment sibling correlation (scor) and standard deviation (SD) distributions share 16 outliers, while the corresponding pretreatment distributions share none. Comparing the pre- and posttreatment CpG outliers, 36 (8%) of SD distributions, and 449/450 (nearly 100%) of scor distributions differ. Combined, these results identify methylation sites within the KIAA1804 and ANAPC2 genes. Each gene also has a highly significant methylation quantitative trait locus (meQTL) (KIAA1804: p

DNA assembly is an integral part of modern synthetic biology, as intricate genetic engineering projects require robust molecular cloning workflows. Golden Gate assembly is a frequently employed DNA assembly methodology that utilizes a Type IIS restriction enzyme and a DNA ligase to generate recombinant DNA constructs from smaller DNA fragments. However, the utility of this methodology has been limited by a lack of resources to guide experimental design. For example, selection of the DNA sequences at fusion sites between fragments is based on broad assembly guidelines or pre-vetted sets of junctions, rather than being customized for a particular application or cloning project. To facilitate the design of robust assembly reactions, we developed a high-throughput DNA sequencing assay to examine reaction outcomes of Golden Gate assembly with T4 DNA ligase and the most commonly used Type IIS restriction enzymes that generate three-base and four-base overhangs. Next, we incorporated these findings into a suite of webtools that design assembly reactions using the experimental data. These webtools can be used to create customized assemblies from a target DNA sequence or a desired number of fragments. Lastly, we demonstrate how using these tools expands the limits of current assembly systems by carrying out one-pot assemblies of up to 35 DNA fragments. Full implementation of the tools developed here enables direct expansion of existing assembly standards for modular cloning systems (e.g. MoClo) as well as the formation of robust new high-fidelity standards.

Nowadays, it is widely acknowledged that low physical activity levels are associated with an increase in terms of both disease recurrence and mortality in cancer survivors. In this light, deciphering those factors able to hamper or facilitate an active lifestyle is crucial in order to increase patients' adherence to physical activity. The purpose of this study was to explore barriers and motivations in a sample of female oncological patients, practising running using the ecological model and compare them with healthy controls. Focus group interviews were conducted at Verona University. Participants were 12 female cancer survivors and 7 matched healthy controls who had participated at "Run for Science" project. The interviews were transcribed verbatim and analyzed using content analysis. Transcripts were categorized according to the ecological model, identifying barriers and motivations as themes. About motivations, three sub-themes were included: personal, interpersonal and environmental/organizational factors. Regarding barriers, another sub-theme was recognized: community/policy factors. Compared to healthy controls, survivors expressed motivations and barriers specifically related to their oncological disease. Running was a challenge with their cancer and a hope to give to other patients. Main barriers were represented by treatment-related side effects, inexperienced trainers and external factors, e.g. delivery of incorrect information. Running programs dedicated to oncological patients should consider intrinsic obstacles, related to cancer and its treatment. The interventions should offer a personalized program performed by qualified trainers, together with a motivational approach able to improve participants' adherence to an active lifestyle.

Abstract GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual research groups were extensively discussed prior, during, and after the Workshop in groups based on discussion themes, before being submitted for publication.

We describe the development and psychometric properties of a new, brief measure of smokers' knowledge of lung cancer screening with low-dose computed tomography (LDCT). Content experts identified key facts smokers should know in making an informed decision about lung cancer screening. Sample questions were drafted and iteratively refined based on feedback from content experts and cognitive testing with ten smokers. The resulting 16-item knowledge measure was completed by 108 heavy smokers in Houston, Texas, recruited from 12/2014 to 09/2015. Item difficulty, item discrimination, internal consistency and test-retest reliability were assessed. Group differences based upon education levels and smoking history were explored. Several items were dropped due to ceiling effects or overlapping constructs, resulting in a 12-item knowledge measure. Additional items with high item uncertainty were retained because of their importance in informed decision making about lung cancer screening. Internal consistency reliability of the final scale was acceptable (KR-20 = 0.66) and test-retest reliability of the overall scale was 0.84 (intraclass correlation). Knowledge scores differed across education levels (F = 3.36, p = 0.04), while no differences were observed between current and former smokers (F = 1.43, p = 0.24) or among participants who met or did not meet the 30-pack-year screening eligibility criterion (F = 0.57, p = 0.45). The new measure provides a brief, valid and reliable indicator of smokers' knowledge of key concepts central to making an informed decision about lung cancer screening with LDCT, and can be part of a broader assessment of the quality of smokers' decision making about lung cancer screening. Keywords: Lung cancer screening, Low-dose computed tomography, Knowledge, Scale development, Shared decision making

In amyotrophic lateral sclerosis (ALS) and animal models of ALS, including SOD1-G93A mice, disassembly of the neuromuscular synapse precedes motor neuron loss and is sufficient to cause a decline in motor function that culminates in lethal respiratory paralysis. We treated SOD1-G93A mice with an agonist antibody to MuSK, a receptor tyrosine kinase essential for maintaining neuromuscular synapses, to determine whether increasing muscle retrograde signaling would slow nerve terminal detachment from muscle. The agonist antibody, delivered after disease onset, slowed muscle denervation, promoting motor neuron survival, improving motor system output, and extending the lifespan of SOD1-G93A mice. These findings suggest a novel therapeutic strategy for ALS, using an antibody format with clinical precedence, which targets a pathway essential for maintaining attachment of nerve terminals to muscle.