RESUMO
We report biallelic missense and frameshift pathogenic variants in the gene encoding human nucleoporin NUP214 causing acute febrile encephalopathy. Clinical symptoms include neurodevelopmental regression, seizures, myoclonic jerks, progressive microcephaly, and cerebellar atrophy. NUP214 and NUP88 protein levels were reduced in primary skin fibroblasts derived from affected individuals, while the total number and density of nuclear pore complexes remained normal. Nuclear transport assays exhibited defects in the classical protein import and mRNA export pathways in affected cells. Direct surface imaging of fibroblast nuclei by scanning electron microscopy revealed a large increase in the presence of central particles (known as "plugs") in the nuclear pore channels of affected cells. This observation suggests that large transport cargoes may be delayed in passage through the nuclear pore channel, affecting its selective barrier function. Exposure of fibroblasts from affected individuals to heat shock resulted in a marked delay in their stress response, followed by a surge in apoptotic cell death. This suggests a mechanistic link between decreased cell survival in cell culture and severe fever-induced brain damage in affected individuals. Our study provides evidence by direct imaging at the single nuclear pore level of functional changes linked to a human disease.
Assuntos
Encefalopatia Aguda Febril/etiologia , Fibroblastos/patologia , Mutação da Fase de Leitura , Canais Iônicos/fisiologia , Mutação de Sentido Incorreto , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Poro Nuclear/patologia , Transporte Ativo do Núcleo Celular , Encefalopatia Aguda Febril/metabolismo , Encefalopatia Aguda Febril/patologia , Apoptose , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Feminino , Fibroblastos/metabolismo , Humanos , Lactente , Masculino , Poro Nuclear/genética , Poro Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/química , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Linhagem , Conformação ProteicaRESUMO
OBJECTIVE: Postoperative hypocalcemia is frequent after total thyroidectomy. The role of pre-operative vitamin D levels in the pathogenesis of this condition has not been studied under the most current guidelines for evaluation of the role of vitamin D in calcium homeostasis. We hypothesized that patients who are vitamin D deficient (VDD) pre-operatively are more likely to suffer from postoperative hypocalcemia, thereby requiring prolonged hospitalization. METHODS: A retrospective chart review of patients undergoing total thyroidectomy at the University of New Mexico Hospital between 2005 and 2014 was performed. Patients who underwent intentional parathyroidectomy were excluded. The study included 30 patients who had a 25-hydroxyvitamin D levels obtained within 12 months before surgery. RESULTS: Twelve patients who were VDD (25-hydroxyvitamin D ≤20 ng/mL) were compared to 18 patients who did not have VDD (non-VDD; 25-hydroxyvitamin D >20 ng/mL). The mean nadir postoperative ionized calcium concentration was lower in the VDD group (0.99 ± 0.10 vs. 1.06 ± 0.06 mmol/L, P = .04) (reference range = 1.15-1.27 mmol/L), as was the postoperative concentration of phosphorus (3.48 ± 0.60 vs. 4.17 ± 0.84 mg/dL, P = .03). VDD patients had a longer length of stay (4.3 ± 4.4 vs. 1.7 ± 1.5 days, P = .03). Three patients in the VDD group required intravenous calcium for treatment of symptomatic hypocalcemia, but none of the non-VDD patients required this intervention (P = .054). CONCLUSION: Pre-operative vitamin D deficiency is associated with an increased risk of postoperative hypocalcemia and a prolonged length of stay in patients undergoing total thyroidectomy. Vitamin D replacement before thyroidectomy may improve postsurgical outcomes in VDD patients. ABBREVIATIONS: BMI = body mass index non-VDD = non-vitamin D deficient PTH = parathyroid hormone VDD = vitamin D deficient.
Assuntos
Hipocalcemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Deficiência de Vitamina D/epidemiologia , Adulto , Feminino , Humanos , Hipertireoidismo/cirurgia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/transplante , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
As a result of the COVID-19 pandemic, the Paul L. Foster School of Medicine incorporated supplementary online learning for 4th year medical students who were unable to participate in clinical activities due to clinical site restrictions to reduce SARS-CoV-2 transmission. An online elective was developed aimed to increase student knowledge of COVID-19: "COVID-19: Utilizing basic sciences to implement what you need to know as a physician." This course required students to further their understanding of SARS-CoV-2 and COVID-19 through directed self-study to identify and summarize the latest scientific literature followed by presenting an online seminar to peers and faculty.
RESUMO
Purpose: Virtual instruction became the primary educational delivery method for pre-clerkship medical students during the COVID-19 pandemic. The aims of this study were to evaluate the effectiveness of a virtual and blended pre-clerkship curriculum and to assess its impact on students. Methods: We surveyed 223 1st- and 2nd-year medical students (MS1s and MS2s) enrolled at the Paul L Foster School of Medicine. We analyzed student satisfaction with their courses, along with summative exam scores, compared to previous academic years. Results: The survey was completed by 125 of 223 students (56%). Most students changed their study methods (78%), experienced technical issues (85%), and had difficulty communicating with faculty (62%). MS1s were significantly more likely than MS2s to report difficulty in adjusting to virtual instruction (p = 0.037) and a negative impact on their learning skills (p = 0.005) and academic performance (p = 0.003). Students reported the virtual environment negatively affected their social skills (77%), connectedness to peers (89%), and professional development (62%). MS1s were more likely than MS2s to perceive a negative effect on their sense of wellness (p = 0.002). The overall satisfaction with the courses was similar to previous academic years. Student performance in the summative examination of the first virtually delivered unit was lower (p = 0.007) than the previous year's cohorts. Conclusion: The difference in MS1s and MS2s perceptions of virtual and blended instruction highlights the importance of face-to-face learning during the first year. Benefits and drawbacks were identified which may help inform educators when designing future learning models. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01723-6.
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Integrating clinical genetic education in physician training is an important strategic approach in the era of genomic medicine. To understand how much the board examinations of the American Board of Medical Specialties contain genomics-related content, a descriptive analysis of 21 exam blueprints was performed. Topics in genomics were not included in 43% of specialty blueprints which shows underrepresentation of clinical genetics in graduate medical education curricula.
RESUMO
Educational strategies to introduce medical students to scientific advances are needed as evidence continues to evolve regarding their clinical application in personalized medicine. Our overall project goal is to design an evidence-based, clinically relevant, personalized medicine curriculum spanning the 4 years of undergraduate medical education.
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A 37-year-old man with AIDS presented with altered mental status four weeks after stopping his medications for Mycobacterium avium-intracellulare (MAI). He had low CD4 cell count and severe hypercalcemia. Bone marrow biopsy revealed bone marrow infiltration by granulomas positive for acid-fast bacilli and cultures grew MAI. His hypercalcemia continued to worsen with the initiation of MAI therapy but we were able to treat it successfully with pamidronate and calcitonin.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Hipercalcemia/diagnóstico por imagem , Hipercalcemia/microbiologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Medula Óssea/microbiologia , Medula Óssea/patologia , Contagem de Linfócito CD4 , Humanos , Hipercalcemia/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Complexo Mycobacterium avium/isolamento & purificaçãoRESUMO
A 47-year-old woman presented with left nipple itch and discomfort. On physical examination she was found to have a 7 mm lesion. She underwent bilateral mammography and bilateral breast ultrasound which were normal. A punch biopsy of the lesion was performed in the office and the specimen submitted to pathology. Histopathological examination showed ectatic vascular spaces lined by flattened, cytologically bland endothelial cells dissecting the dermal collagen. Evident lymphatic valves were present within the vascular spaces confirming that the vessels were lymphatic in nature. The diagnosis of acquired progressive lymphangioma (benign lymphangioendothelioma) was rendered.
Assuntos
Neoplasias da Mama/diagnóstico , Linfangioma/diagnóstico , Mamilos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfangioma/patologia , Linfangioma/cirurgia , Pessoa de Meia-Idade , Mamilos/patologia , Mamilos/cirurgiaRESUMO
Abstract A 37-year-old man with AIDS presented with altered mental status four weeks after stopping his medications for Mycobacterium avium-intracellulare (MAI). He had low CD4 cell count and severe hypercalcemia. Bone marrow biopsy revealed bone marrow infiltration by granulomas positive for acid-fast bacilli and cultures grew MAI. His hypercalcemia continued to worsen with the initiation of MAI therapy but we were able to treat it successfully with pamidronate and calcitonin.