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BACKGROUND: Simulation-based learning has been a valuable integrated part of simulation curricula. Simulation modalities include high-fidelity simulation (HFS), clinical skills (SK), standardized patients (SP), hybrid and combined simulation. HFS and SK are usually taught face-to-face and require specialized equipment. In response to the COVID-19 pandemic and lockdowns, efforts to develop distributed screen-based high-fidelity simulation accelerated to provide enhanced remote learning. The authors set out to develop cost-effective, high fidelity, user-friendly software to assist medical students in developing cardiac auscultation skills and clinical reasoning. Physical manikins are expensive, where costs range from $23,000-$250,000 each. The following applications: Heart Auscultation Trainer (HAT), Lung Auscultation Trainer (LAT), and a distributed screen-based high-fidelity simulator (DSB-HFS) comprise a comprehensive medical education software package developed and implemented at the University of South Dakota Sanford School of Medicine (USD SSOM). The HAT application was specifically evaluated in this project. METHODS: HAT and LAT were developed for Macintosh, Windows, and Linux operating systems. Both applications feature an on-screen human torso on which users can auscultate heart and lung sounds. Users can select from 52 heart and 15 lung conditions, built-in lessons, a testing mode, and sonograms. DSB-HFS is a network of applications distributed over the internet. Learners can view a patient avatar, perform basic physical exam, review vital signs, and order treatments. An instructor can change avatar parameters in accordance to administered treatments. Information exchange between the instructor and learners occur via a cloud-based connection. Effectiveness, simplicity, and cross-platform usability of HAT was assessed via survey. DSB-HFS has been developed, tested, and piloted. As of December 2022, DSB-HFS was under next phase of development. RESULTS: The 11-question survey was distributed to medical students with an 81.4% response rate. More than half of respondents used HAT at least once per week. Most respondents agreed that: installation was relatively easy, the Graphic User Interface was easy to use, built-in lessons were somewhat useful, and he/she would recommend HAT to other students. Narrative feedback was collected to improve future iterations of HAT. No data were collected regarding LAT or the DSB-HFS simulator. CONCLUSION: The suite of applications was found to be effectively implemented and was a cost-saving addition to a remote software package available to medical students at the USD SSOM. HAT was perceived by first-time users to be an easy to use and effective learning tool. User-generated feedback will be implemented to improve applications. Limitations to this project include a lack of quantitative data.
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COVID-19 , Educación Médica , Medicina , Femenino , Humanos , Pandemias , Control de Enfermedades TransmisiblesRESUMEN
A 64-year-old female presented to the emergency department (ED) with complaints of two days of intermittent fever and chills, progressively worsening back pain, and hematochezia. Initial evaluation and computer tomography (CT) imaging work up revealed a hypervascular and necrotic appearing pelvic mass, measuring 11.7 x 7.8 x 9.7 cm, closely associated with the inferior mesenteric vein (IMV) in conjunction with portal venous gas. Flexible sigmoidoscopy with biopsy was performed to identify the etiology of the lesion and revealed an ulcerated non-obstructing mass in the recto-sigmoid colon measuring 3 cm in length and involving 1/3 of lumen circumference with oozing present. Interventional radiology (IR) embolization of the feeding vessels was done pre-operatively due to high vascularity of the mass. Pathology of the mass was consistent with a malignant solitary fibrous tumor.
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Tumores Fibrosos Solitarios , Femenino , Humanos , Persona de Mediana Edad , Tumores Fibrosos Solitarios/diagnóstico por imagen , Tumores Fibrosos Solitarios/cirugía , Biopsia , Vena Porta , Venas Mesentéricas/diagnóstico por imagenRESUMEN
One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7. EOM-derived and LEG-derived EECD34 cells were treated with vehicle, retinoic acid, the RXR agonist bexarotene, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG-derived cells expressed desmin and fused when treated with retinoic acid compared to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We hypothesize that retinoic acid signaling aids in the maintenance of large numbers of undifferentiated myogenic precursor cells in the EOM, which would be required to maintain EOM normalcy throughout a lifetime of myonuclear turnover.
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Desarrollo de Músculos/fisiología , Músculo Esquelético/citología , Mioblastos/citología , Músculos Oculomotores/citología , Receptores X Retinoide/metabolismo , Tretinoina/farmacología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Proteínas de Homeodominio/metabolismo , Técnicas In Vitro , Queratolíticos/farmacología , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Músculos Oculomotores/efectos de los fármacos , Músculos Oculomotores/metabolismo , Factor de Transcripción PAX7/metabolismo , Factores de Transcripción/metabolismo , Proteína del Homeodomínio PITX2RESUMEN
Friedreich's Ataxia (FRDA) is a neuromuscular degenerative disorder caused by trinucleotide expansions in the first intron of the frataxin (FXN) gene, resulting in insufficient levels of functional FNX protein. Deficits in FXN involve mitochondrial disruptions including iron-sulfur cluster synthesis and impaired energetics. These studies were to identify unique protein-protein interactions with FXN to better understand its function and design therapeutics. Two complementary approaches were employed, BioID and Co-IP, to identify protein interactions with FXN at the direct binding, indirect binding, and non-proximal levels. Forty-one novel protein interactions were identified by BioID and IP techniques. The FXN protein landscape was further analyzed incorporating both interaction type and functional pathways using a maximum path of 6 proteins with a potential direct interaction between FXN and NFS1. Probing the intersection between FXN-protein landscape and biological pathways associated with FRDA, we identified 41 proteins of interest. Peroxiredoxin 3 (Prdx3) was chosen for further analysis because of its role in mitochondrial oxidative injury. Our data has demonstrated the strengths of employing complementary methods to identify a unique interactome for FXN. Our data provides new insights into FXN function and regulation, a potential direct interaction between FXN and NFS1, and pathway interactions between FXN and Prdx3.
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Recent microarray and RNAseq experiments provided evidence that glial derived neurotrophic factor (GDNF) levels were decreased in extraocular muscles from human strabismic subjects compared to age-matched controls. We assessed the effect of sustained GDNF treatment of the superior rectus muscles of rabbits on their physiological and morphological characteristics, and these were compared to naïve control muscles. Superior rectus muscles of rabbits were implanted with a sustained release pellet of GDNF to deliver 2µg/day, with the contralateral side receiving a placebo pellet. After one month, the muscles were assessed using in vitro physiological methods. The muscles were examined histologically for alteration in fiber size, myosin expression patterns, neuromuscular junction size, and stem cell numbers and compared to age-matched naïve control muscles. GDNF resulted in decreased force generation, which was also seen on the untreated contralateral superior rectus muscles. Muscle relaxation times were increased in the GDNF treated muscles. Myofiber mean cross-sectional areas were increased after the GDNF treatment, but there was a compensatory increase in expression of developmental, neonatal, and slow tonic myosin heavy chain isoforms. In addition, in the GDNF treated muscles there was a large increase in Pitx2-positive myogenic precursor cells. One month of GDNF resulted in significant extraocular muscle adaptation. These changes are interesting relative to the decreased levels of GDNF in the muscles from subjects with strabismus and preliminary data in infant non-human primates where sustained GDNF treatment produced a strabismus. These data support the view that GDNF has the potential for improving eye alignment in subjects with strabismus.
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Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Músculos Oculomotores/efectos de los fármacos , Músculos Oculomotores/fisiología , Animales , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Cadenas Pesadas de Miosina/genética , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/metabolismo , Músculos Oculomotores/citología , Músculos Oculomotores/metabolismo , Conejos , Factores de TiempoRESUMEN
Facioscapulohumeral muscular dystrophy (FSHD) is a genetically dominant myopathy caused by mutations that disrupt repression of the normally silent DUX4 gene, which encodes a transcription factor that has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a p53-knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53 dependence of DUX4 using various in vitro and in vivo models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4 does not lead to activation of the p53 pathway. DUX4 does lead to expression of the classic p53 target gene Cdkn1a (p21) but in a p53-independent manner. Meta-analysis of 5 publicly available data sets of DUX4 transcriptional profiles in both human and mouse cells shows no evidence of p53 activation, and further reveals that Cdkn1a is a mouse-specific target of DUX4. When the inducible DUX4 mouse model is crossed onto the p53-null background, we find no suppression of the male-specific lethality or skin phenotypes that are characteristic of the DUX4 transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.