A Call to Action: Using Curriculum Mapping at Four Medical Schools in Massachusetts to Advance Serious Illness Communication Training in Undergraduate Medical Education.

Background: Practicing physicians require serious illness communication (SIC) skills to ensure high-quality, humanistic care for patients and families as they face life-changing medical decisions. However, a majority of U.S. medical schools do not require formal training in SIC and fail to provide students deliberate practice before graduation. The Massachusetts Medical Schools' Collaborative was created to ensure that students receive foundational SIC training in undergraduate medical education. This Collaborative developed a curriculum-mapping tool to assess SIC at four medical schools. Objective: We aimed to understand existing educational activities across four medical schools and identify opportunities to build longitudinal, developmentally based curricular threads in SIC. Design: From July 2019 to April 2021, faculty, staff, and medical students assessed current educational activities related to five core competencies in SIC, adapted for students from national competencies for palliative medicine fellows, using a curriculum mapping tool. Measurements: The group selected 23 keywords and collected metrics to describe the timing, instruction and assessment for each school's educational activities. Results: On average, there were only 40 hours of required curricula in SIC over four years. Over 80% of relevant SIC hours occurred as elective experiences, mostly during the postclerkship phase, with limited capacity in these elective experiences. Only one school had SIC educational activities during the clerkship phase when students are developing clinical competencies. Assessment methods focused on student participation, and no school-assessed clinical performance in the clerkship or postclerkship phase. Conclusions: Medical schools are failing to consistently train and ensure basic competency in effective, compassionate SIC. Curriculum mapping allows schools to evaluate their current state on a particular topic such as SIC, ensure proper assessment, and evaluate curricular changes over time. Through the deliberate inclusion of SIC competencies in longitudinal curriculum design, we can fill this training gap and create best practices in undergraduate medical education.

Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites.

In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.

Single Cell Transcriptomics-Informed Induced Pluripotent Stem Cells Differentiation to Tenogenic Lineage.

During vertebrate embryogenesis, axial tendons develop from the paraxial mesoderm and differentiate through specific developmental stages to reach the syndetome stage. While the main roles of signaling pathways in the earlier stages of the differentiation have been well established, pathway nuances in syndetome specification from the sclerotome stage have yet to be explored. Here, we show stepwise differentiation of human iPSCs to the syndetome stage using chemically defined media and small molecules that were modified based on single cell RNA-sequencing and pathway analysis. We identified a significant population of branching off-target cells differentiating towards a neural phenotype overexpressing Wnt. Further transcriptomics post-addition of a WNT inhibitor at the somite stage and onwards revealed not only total removal of the neural off-target cells, but also increased syndetome induction efficiency. Fine-tuning tendon differentiation in vitro is essential to address the current challenges in developing a successful cell-based tendon therapy.

Modeling Traumatic Brain Injury in Human Cerebral Organoids.

Traumatic brain injury (TBI) is a head injury that disrupts the normal brain structure and function. TBI has been extensively studied using various in vitro and in vivo models. Most of the studies have been done with rodent models, which may respond differently to TBI than human nerve cells. Taking advantage of the recent development of cerebral organoids (COs) derived from human induced pluripotent stem cells (iPSCs), which resemble the architecture of specific human brain regions, here, we adapted the controlled cortical impact (CCI) model to induce TBI in human COs as a novel in vitro platform. To adapt the CCI procedure into COs, we have developed a phantom brain matrix, matching the mechanical characteristics of the brain, altogether with an empty mouse skull as a platform to allow the use of the stereotactic CCI equipment on COs. After the CCI procedure, COs were histologically prepared to evaluate neurons and astrocyte populations using the microtubule-associated protein 2 (MAP2) and the glial fibrillary acidic protein (GFAP). Moreover, a marker of metabolic response, the neuron-specific enolase (NSE), and cellular death using cleaved caspase 3 were also analyzed. Our results show that human COs recapitulate the primary pathological changes of TBI, including metabolic alterations related to neuronal damage, neuronal loss, and astrogliosis. This novel approach using human COs to model TBI in vitro holds great potential and opens new alternatives for understanding brain abnormalities produced by TBI, and for the development and testing of new therapeutic approaches.

Formación de recursos humanos en enfermería. Universidad 11 de noviembre, Cabinda, Angola / Training of human resources in nursing at November 11th University, Cabinda, Angola

RESUMEN Introducción: ante la creciente necesidad de salvaguardar la seguridad de las personas que acuden diariamente a recibir servicios médicos para prevenir enfermedades o mantener y recuperar la salud, los gobiernos deben garantizar la formación de recursos humanos competentes que brinden atención de calidad; el enfermero constituye la piedra angular en el sistema de salud. Objetivo: evaluar la formación de recursos humanos en enfermería en la Universidad 11 de noviembre, en Cabinda, Angola. En el período comprendido entre 2015-2018. Métodos: se realizó una investigación descriptiva, retrospectiva. Los datos se obtuvieron a través de la revisión bibliográfica, entrevistas a fundadores de la escuela y documentos de la secretaria docente. Resultados: se encontraron en proceso de formación 337 estudiantes de los diferentes años, el 24,6 fueron de segundo año, se presentaron a exámenes estatales 129 de los cuales el 44 % obtuvo calificaciones superiores a 15 valores. Conclusiones: mediante el proyecto de cooperación Cuba - Angola se han graduado 129 Licenciados en Enfermería, los cuales se encuentran insertados en el sistema de salud de Cabinda, lo que contribuyó a elevar los niveles de salud de la población, se evaluó como muy efectivo la formación de recursos humanos de los profesionales en este sector.

ABSTRACT Introduction: before the growing need to preserve the safety of people who come daily to receive healthcare services for the purpose of preventing diseases or maintaining and recovering health, governments must ensure the training of competent human resources who provide quality care, where nurses represent the cornerstone in the healthcare system. Objective: to assess the training of human resources in nursing at November 11th University, Cabinda, Angola during 2015-2018. Methods: a descriptive, retrospective research was conducted. Data were collected through literature review, interviews with founders of the school and documents from the office of the teaching registrar. Results: students from different academic years (337) were found to be in the training process, 24,6 % were second-academic year students, 129 of them took state exams where 44% obtained grades higher than 15 values. Conclusions: throughout Cuba - Angola cooperation project, 129 students have been graduated in Nursing Degree, who are inserted in the healthcare system of Cabinda, contributing to the increase of the levels of health of the population, evaluating as very effective the development of human resources of these professionals of the healthcare sector.

Mitochondrial transplant to replenish damaged mitochondria: A novel therapeutic strategy for neurodegenerative diseases?

Neurodegenerative diseases are currently some of the most debilitating and incurable illness, including highly prevalent disorders, such as Alzheimer's and Parkinson's disease. Despite impressive advances in understanding the molecular basis of neurodegenerative diseases, several clinical trials have failed in identifying drugs that successfully delay or stop disease progression. New targets are likely necessary to successfully combat these devastating diseases. In this chapter, we review the evidence indicating that impairment in the cellular energy machinery in the form of mitochondrial damage and dysfunction may be at the root of neurodegeneration. We also propose that transplant of functional isolated mitochondria may overcome the energetic damage and delay the progression of neurodegenerative diseases.

Relationship of vitamin D blood concentration with muscle mass and cognitive function in postmenopausal women.

INTRODUCTION: Low levels of vitamin D have been associated with muscle mass loss and cognitive function alteration. OBJECTIVE: To find out the relationship of vitamin D blood levels with muscle mass and cognitive function in postmenopausal women. MATERIALS AND METHODS: Ninety-nine postmenopausal women aged ≥ 50 years were studied. Calf circumference, and tricipital, bicipital, subscapular and suprailiac skinfolds were measured. Arm muscle area, bone-free arm muscle area, and muscle mass were calculated. The short physical performance battery (SPPB) was performed, and the sarcopenia rapid diagnostic questionnaire (SARC-F), as well as the Mini Mental State Examination (MMSE) were applied. A blood sample was taken to measure vitamin D blood concentration. For statistical analysis, Mann-Whitney's U-test and Spearman's correlation analysis were used. RESULTS: It was found that, the older the age, the higher the vitamin D levels, as well as higher SARC-F score. Vitamin D levels were negatively correlated with grip strength and SPPB. There was a negative correlation between vitamin D levels and MMSE global score. CONCLUSIONS: Vitamin D did not have a positive influence on muscle mass. A better MMSE performance was observed in those with lower vitamin D levels.

INTRODUCCIÓN: Las concentraciones bajas de vitamina D se han asociado con la pérdida de masa muscular y la alteración de la función cognitiva. OBJETIVO: Conocer la relación de la concentración sanguínea de vitamina D con la masa muscular y la función cognitiva en mujeres posmenopáusicas. MATERIALES Y MÉTODOS: Se estudiaron 99 mujeres posmenopáusicas ≥ 50 años. Se midió la circunferencia de la pantorrilla, los pliegues cutáneos tricipital, bicipital, subescapular y suprailíaco. Se calcularon: el área muscular del brazo, el área muscular libre de hueso y la masa muscular total. Se realizó la prueba corta de desempeño físico (PCDF), se aplicó el cuestionario de diagnóstico rápido de sarcopenia (SARC-F) y el Mini Examen del Estado Mental (MMSE). Se tomó una muestra de sangre para medir la concentración de vitamina D en sangre. Para el análisis estadístico se utilizó la prueba U de Mann-Whitney y análisis de correlación de Spearman. RESULTADOS: Se encontró que a mayor edad hubieron mayores concentraciones de vitamina D y mayor puntaje SARC-F. Las concentraciones de vitamina D se correlacionaron negativamente con la fuerza de agarre, la PCDF y la puntuación total del MMSE. CONCLUSIONES: La vitamina D no tuvo una influencia positiva sobre la masa muscular. Se observó un mejor desempeño en el MMSE en aquellas con concentraciones más bajas de vitamina D.

Riesgos en Enfermería en salón de operaciones del hospital provincial de Cabinda / Risks of nursing care in the operating room of Cabinda provincial hospital

RESUMEN Introducción: el término riesgo en el ámbito de la sanidad hace referencia inmediata a un peligro para el paciente en forma de resultado no esperado y casi siempre desfavorable, el ejercicio responsable de la Enfermería está delimitado por el cumplimiento estricto de las normas morales y legales, la calidad y la eficiencia son responsabilidad de los profesionales de Enfermería, como factores protectores en la prevención del error, en los últimos tiempos se ha realizado una reflexión más profunda sobre la presencia de los eventos adversos y el consecuente error sanitario. Objetivo: Determinar la existencia de riesgos y su manejo en el salón de operaciones del hospital 1º. de Mayo de Cabinda en el periodo marzo a mayo de 2017. Métodos: se realizó un estudio descriptivo prospectivo. El universo estuvo constituido por las 17 enfermeras que laboraron en el salón de operaciones, y la Jefa de Enfermeras. De las intervenciones quirúrgicas realizadas en el período elegido se observaron las de abril. Resultados: se constató que la mayor cantidad de enfermeras que trabajaron en el salón tenían categoría técnica y más de 10 años en ese servicio, se identificaron riesgos administrativos, médicos y biológicos, relacionados con los métodos de desinfección, la permanencia de las puertas abiertas, recolección de los residuales, Conclusiones: ¿cuál fue? por lo que se recomienda elaborar una estrategia administrativa para elevar la seguridad de los pacientes en el ámbito quirúrgico.

ABSTRACT Introduction: the term risk in the field of health services refers immediately to a hazard for the patient in an unexpected way and almost always having an unfavorable result, the responsible practice of nursing is delimited by the strict compliance with moral and legal standards, quality and efficiency are responsibilities of the nursing personnel, as protective factors in the prevention of errors in the care of patients, in recent times there has been a deeper reflection on the presence of adverse events and the resulting error in the care of patients Objective: to determine the existence of risks and their management in the operating room at 1º de Mayo hospital in Cabinda, Angola, from March to May 2017. Methods: the target group included 17 nurses who worked in the operating room, and the Chief Nurse. Out of the surgical interventions performed in the chosen period, those completed on April were observed. Results: it was found that the largest number of nurses who worked in the operating room completed the proper technical rank and have more than 10 years of experience in the surgical and administrative service, the medical and biological risks were identified, mainly the ones related to disinfection methods, the permanence of open doors and collection of residuals. Conclusions: it is recommended to develop an administrative strategy to increase the safety of patients in the surgical room.

Low-dose administration of bleomycin leads to early alterations in lung mechanics.

NEW FINDINGS: What is the central question of this study? When do alterations in pulmonary mechanics occur following chronic low-dose administration of bleomycin? What is the main finding and its importance? Remarkably, we report changes in lung mechanics as early as day 7 that corresponded to parameters determined from single-frequency forced oscillation manoeuvres and pressure-volume loops. These changes preceded substantial histological changes or changes in gene expression levels. These findings are significant to refine drug discovery in idiopathic pulmonary fibrosis, where preclinical studies using lung function parameters would enhance the translational potential of drug candidates where lung function readouts are routinely performed in the clinic. ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is the most widespread form of interstitial lung disease and, currently, there are only limited treatment options available. In preclinical animal models of lung fibrosis, the effectiveness of experimental therapeutics is often deemed successful via reductions in collagen deposition and expression of profibrotic genes in the lung. However, in clinical studies, improvements in lung function are primarily used to gauge the success of therapeutics directed towards IPF. Therefore, we examined whether changes in respiratory system mechanics in the early stages of an experimental model of lung fibrosis can be used to refine drug discovery approaches for IPF. C57BL/6J mice were administered bleomycin (BLM) or a vehicle control i.p. twice a week for 4 weeks. At 7, 14, 21, 28 and 33 days into the BLM treatment regimen, indices of respiratory system mechanics and pressure-volume relationships were measured. Concomitant with these measurements, histological and gene analyses relevant to lung fibrosis were performed. Alterations in respiratory system mechanics and pressure-volume relationships were observed as early as 7 days after the start of BLM administration. Changes in respiratory system mechanics preceded the appearance of histological and molecular indices of lung fibrosis. Administration of BLM leads to early changes in respiratory system mechanics that coincide with the appearance of representative histological and molecular indices of lung fibrosis. Consequently, these data suggest that dampening the early changes in respiratory system mechanics might be used to assess the effectiveness of experimental therapeutics in preclinical animal models of lung fibrosis.

Transition from resident robotic training program to clinical practice: robotic-assisted radical prostatectomy benchmark for perioperative safety.

OBJECTIVE: To analyze the perioperative safety and outcomes of the first 100 robotic-assisted radical prostatectomies (RARPs) performed by a resident trained surgeon entering directly into practice. SUBJECTS AND METHODS: Following a mentorship-based urology residency training program, the perioperative safety and outcomes of 100 consecutive RARPs were analyzed. Intraoperative complications, surgical pathology results, hospital course, and catheter removal times were all monitored. Urinary catheter time was considered prolonged if left in place for longer than 14 days. Surgical complications were scored using the Clavien grading system. RESULTS: The resident performed portions of 51 RARPs during the training program in resident years 2-5, including 17 as a chief resident under the guidance of a fellowship-trained robotic surgeon. One hundred RARPs were performed following residency training over a 17-month period (mean age, 60 years; mean body mass index, 29 kg/m(2)). Positive margin rate was 21%, and blood transfusion rate was 5%. Clavien grade 1-4 complication rates were 5%, 9%, 1%, and 1%, respectively. There was one intraoperative rectal injury and one conversion to an open operation. Five percent of patients required a urinary catheter longer than 14 days secondary to anastomotic leakage. There were no re-admissions or re-operations in the series. CONCLUSIONS: The current study serves as a benchmark for physicians entering practice directly from resident training. Mentorship-based residency programs and early console experience may be factors in contributing to perioperative safety and outcomes with newly trained physicians.

Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor.

Targeting the mammalian target of rapamycin (mTOR) protein is a promising strategy for cancer therapy. The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. We compared rapamycin with PP242, an inhibitor of the active site of mTOR in both TORC1 and TORC2 (hereafter referred to as TORC1/2), in models of acute leukemia harboring the Philadelphia chromosome (Ph) translocation. We demonstrate that PP242, but not rapamycin, causes death of mouse and human leukemia cells. In vivo, PP242 delays leukemia onset and augments the effects of the current front-line tyrosine kinase inhibitors more effectively than does rapamycin. Unexpectedly, PP242 has much weaker effects than rapamycin on the proliferation and function of normal lymphocytes. PI-103, a less selective TORC1/2 inhibitor that also targets phosphoinositide 3-kinase (PI3K), is more immunosuppressive than PP242. These findings establish that Ph(+) transformed cells are more sensitive than normal lymphocytes to selective TORC1/2 inhibitors and support the development of such inhibitors for leukemia therapy.