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Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only approximately 92 reported. Spinal AT/RT in adults is particularly rare. Here, we present the case of a 50-year-old patient diagnosed with AT/RT of the spine. Initially, they were diagnosed and treated for a spinal ependymoma. However, after 10 years, a recurrence was detected through magnetic resonance imaging (MRI) and the tumor was reclassified as AT/RT. We discuss the significance of SMARCB1 gene mutations in diagnosing AT/RT and describe our unique treatment approach involving surgery, radiation and anti-PD1 therapy in this patient.
Atypical teratoid rhabdoid tumors (AT/RT) are rare and serious cancers that affect the brain and spine, and mostly occur in children. AT/RT are rare in adults, with only about 92 cases reported. Our article tells the story of a 50-year-old patient, who was diagnosed with a spinal tumor, initially classified as an ependymoma. Ten years later, the tumor recurred, and was found on routine surveillance imaging. After pathological examination of the recurrent tumor, it was diagnosed as AT/RT. The initial tissue was re-examined, and the original tumor was reclassified as an AT/RT. We explain why a gene called SMARCB1 is important for diagnosing AT/RT. Additionally, we share details about the treatments utilized: including surgery, radiation, and medicines that stimulate the immune system to kill cancer cells. This case highlights the challenges and treatments for this rare cancer in adults.
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Neoplasias do Sistema Nervoso Central , Tumor Rabdoide , Teratoma , Humanos , Pessoa de Meia-Idade , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/genética , Tumor Rabdoide/terapia , Proteína SMARCB1/genética , Teratoma/diagnóstico por imagem , Teratoma/genética , Teratoma/cirurgiaRESUMO
Importance: Board certification can have broad implications for candidates' career trajectories, and prior research has found sociodemographic disparities in pass rates. Barriers in the format and administration of the oral board examinations may disproportionately affect certain candidates. Objective: To characterize oral certifying examination policies and practices of the 16 Accreditation Council for Graduate Medical Education (ACGME)-accredited specialties that require oral examinations. Design, Setting, and Participants: This cross-sectional study was conducted from March 1 to April 15, 2023, using data on oral examination practices and policies (examination format, dates, and setting; lactation accommodations; and accommodations for military deployment, family emergency, or medical leave) as well as the gender composition of the specialties' boards of directors obtained from websites, telephone calls and email correspondence with certifying specialists. The percentages of female residents and residents of racial and ethnic backgrounds who are historically underrepresented in medicine (URM) in each specialty as of December 31, 2021, were obtained from the Graduate Medical Education 2021 to 2022 report. Main Outcome and Measures: For each specialty, accommodation scores were measured by a modified objective scoring system (score range: 1-13, with higher scores indicating more accommodations). Poisson regression was used to assess the association between accommodation score and the diversity of residents in that specialty, as measured by the percentages of female and URM residents. Linear regression was used to assess whether gender diversity of a specialty's board of directors was associated with accommodation scores. Results: Included in the analysis were 16 specialties with a total of 46 027 residents (26 533 males [57.6%]) and 233 members of boards of directors (152 males [65.2%]). The mean (SD) total accommodation score was 8.28 (3.79), and the median (IQR) score was 9.25 (5.00-12.00). No association was found between test accommodation score and the percentage of female or URM residents. However, for each 1-point increase in the test accommodation score, the relative risk that a resident was female was 1.05 (95% CI, 0.96-1.16), and the relative risk that an individual was a URM resident was 1.04 (95% CI, 1.00-1.07). An association was found between the percentage of female board members and the accommodation score: for each 10% increase in the percentage of board members who were female, the accommodation score increased by 1.20 points (95% CI, 0.23-2.16 points; P = .03). Conclusions and Relevance: This cross-sectional study found considerable variability in oral board examination accommodations among ACGME-accredited specialties, highlighting opportunities for improvement and standardization. Promoting diversity in leadership bodies may lead to greater accommodations for examinees in extenuating circumstances.
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Certificação , Humanos , Estudos Transversais , Feminino , Masculino , Certificação/estatística & dados numéricos , Estados Unidos , Conselhos de Especialidade Profissional/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Avaliação Educacional/métodos , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Medicina/estatística & dados numéricos , AdultoRESUMO
Of the hundreds of E3 ligases found in the human genome, the RING-between RING (RBR) E3 ligase in the LUBAC (linear ubiquitin chain assembly complex) complex HOIP (HOIL-1-interacting protein or RNF31), contains a unique domain called LDD (linear ubiquitin chain determining domain). HOIP is the only E3 ligase known to form linear ubiquitin chains, which regulate inflammatory responses and cell death via activation of the NF-κB pathway. We identified an amino acid sequence within the RNF216 E3 ligase that shares homology to the LDD domain found in HOIP (R2-C). Here, we show that the R2-C domain of RNF216 promotes self-assembly of all ubiquitin chains, with a dominance for those assembled via K63-linkages. Deletion of the R2-C domain altered RNF216 localization, reduced dendritic complexity and changed the distribution of apical dendritic spine morphology types in primary hippocampal neurons. These changes were independent of the RNF216 RBR catalytic activity as expression of a catalytic inactive version of RNF216 had no effect. These data show that the R2-C domain of RNF216 diverges in ubiquitin assembly function from the LDD of HOIP and and functions independently of RNF216 catalytic activity to regulate dendrite development in neurons.
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OBJECTIVE: The rates of women and underrepresented racial and ethnic minority (UREM) students successfully matching into neurosurgical residency are extremely low and do not reflect the makeup of the general population. As of 2019, only 17.5% of neurosurgical residents in the United States were women, 4.95% were Black or African American, and 7.2% were Hispanic or Latinx. Earlier recruitment of UREM students will help to diversify the neurosurgical workforce. Therefore, the authors developed a virtual educational event for undergraduate students entitled "Future Leaders in Neurosurgery Symposium for Underrepresented Students'' (FLNSUS). The primary objectives of the FLNSUS were to expose attendees to 1) neurosurgeons from diverse gender, racial, and ethnic backgrounds; 2) neurosurgical research; 3) opportunities for neurosurgical mentorship; and 4) information about life as a neurosurgeon. The authors hypothesized that the FLNSUS would increase student self-confidence, provide exposure to the specialty, and reduce perceived barriers to a neurosurgical career. METHODS: To measure the change in participant perceptions of neurosurgery, pre- and postsymposium surveys were administered to attendees. Of the 269 participants who completed the presymposium survey, 250 participated in the virtual event and 124 completed the postsymposium survey. Paired pre- and postsurvey responses were used for analysis, yielding a response rate of 46%. To assess the impact of participant perceptions of neurosurgery as a field, pre- and postsurvey responses to questions were compared. The change in response was analyzed, and a nonparametric sign test was performed to check for significant differences. RESULTS: According to the sign test, applicants showed increased familiarity with the field (p < 0.001), increased confidence in their abilities to become neurosurgeons (p = 0.014), and increased exposure to neurosurgeons from diverse gender, racial, and ethnic backgrounds (p < 0.001 for all categories). CONCLUSIONS: These results reflect a significant improvement in student perceptions of neurosurgery and suggest that symposiums like the FLNSUS may promote further diversification of the field. The authors anticipate that events promoting diversity in neurosurgery will lead to a more equitable workforce that will ultimately translate to enhanced research productivity, cultural humility, and patient-centered care in neurosurgery.
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Internato e Residência , Neurocirurgia , Humanos , Feminino , Estados Unidos , Masculino , Neurocirurgia/educação , Etnicidade , Escolha da Profissão , Grupos Minoritários , Procedimentos NeurocirúrgicosRESUMO
The NIMH Healthy Research Volunteer Dataset is a collection of phenotypic data characterizing healthy research volunteers using clinical assessments such as assays of blood and urine, mental health assessments, diagnostic and dimensional measures of mental health, cognitive and neuropsychological functioning, structural and functional magnetic resonance imaging (MRI), along with diffusion tensor imaging (DTI), and a comprehensive magnetoencephalography battery (MEG). In addition, blood samples of healthy volunteers are banked for future analyses. All data collected in this protocol are broadly shared in the OpenNeuro repository, in the Brain Imaging Data Structure (BIDS) format. In addition, task paradigms and basic pre-processing scripts are shared on GitHub. There are currently few open access MEG datasets, and multimodal neuroimaging datasets are even more rare. Due to its depth of characterization of a healthy population in terms of brain health, this dataset may contribute to a wide array of secondary investigations of non-clinical and clinical research questions.
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Imagem de Tensor de Difusão , Magnetoencefalografia , Encéfalo/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , National Institute of Mental Health (U.S.) , Neuroimagem/métodos , Estados UnidosRESUMO
Protein ubiquitination is a posttranslational modification that plays an integral part in mediating diverse cellular functions. The process of protein ubiquitination requires an enzymatic cascade that consists of a ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2) and an E3 ubiquitin ligase (E3). There are an estimated 600-700 E3 ligase genes representing ~5% of the human genome. Not surprisingly, mutations in E3 ligase genes have been observed in multiple neurological conditions. We constructed a comprehensive atlas of disrupted E3 ligase genes in common (CND) and rare neurological diseases (RND). Of the predicted and known human E3 ligase genes, we found ~13% were mutated in a neurological disorder with 83 total genes representing 70 different types of neurological diseases. Of the E3 ligase genes identified, 51 were associated with an RND. Here, we provide an updated list of neurological disorders associated with E3 ligase gene disruption. We further highlight research in these neurological disorders and discuss the advanced technologies used to support these findings.