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BACKGROUND: Little is known about the relationship among systemic racism, psychological symptoms (depression, anxiety, and/or post-traumatic stress disorders), and burnout in healthcare workers (HCWs). OBJECTIVE: To determine whether distress related to awareness of systemic racism contributes to psychological symptoms and/or burnout in HCWs. We explored whether this form of racism-related distress may moderate the relationship between race, ethnicity, psychological symptoms, and burnout. DESIGN: A cross-sectional survey was conducted from November 19, 2020, through January 11, 2021. Statistical analysis was conducted from May 3, 2022, to June 15, 2022. PARTICIPANTS: Frontline HCWs at an urban tertiary care hospital in New York City. MAIN MEASURES: Distress related to awareness of systemic racism (SR) and racial disparities in COVID-19 outcomes (RD), psychological symptoms, and burnout. KEY RESULTS: Two thousand one of 4654 HCWs completed the survey (response rate 43.0%). Most HCWs reported experiencing distress related to awareness of systemic racism (1329 [66.4%]) and to racial disparities in COVID-19 outcomes (1137 [56.8%]). Non-Hispanic Black participants (SR odds ratio (OR) 2.84, p < .001; RD OR 2.34, p < .001), women (SR OR 1.35, p = .01; RD OR 1.67, p < .001), and those with history of mental illness (SR OR 2.13, p < .001; RD OR 1.66, p < .001) were more likely to report SR- and RD-related distress, respectively. HCWs who experienced "quite-a-bit to extreme" SR-related distress were more likely to screen positive for psychological symptoms (OR 5.90, p < .001) and burnout (OR 2.26, p < .001). CONCLUSIONS: Our findings suggest that distress related to awareness of systemic racism, not race/ethnicity, was associated with experiencing psychological symptoms and burnout in HCWs. As the medical community continues to critically examine the role of systemic racism in healthcare, our work is a first step in characterizing its toll on the psychological well-being of HCWs.
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Esgotamento Profissional , COVID-19 , Humanos , Feminino , Racismo Sistêmico , Estudos Transversais , Cidade de Nova Iorque/epidemiologia , Pandemias , Pessoal de Saúde , Esgotamento Profissional/epidemiologiaRESUMO
This review article provides a comprehensive overview of a novel Sindbis virus vaccine platform as potential immunotherapy for ovarian cancer patients. Ovarian cancer is the most lethal of all gynecological malignancies. The majority of high-grade serous ovarian cancer (HGSOC) patients are diagnosed with advanced disease. Current treatment options are very aggressive and limited, resulting in tumor recurrences and 50-60% patient mortality within 5 years. The unique properties of armed oncolytic Sindbis virus vectors (SV) in vivo have garnered significant interest in recent years to potently target and treat ovarian cancer. We discuss the molecular biology of Sindbis virus, its mechanisms of action against ovarian cancer cells, preclinical in vivo studies, and future perspectives. The potential of Sindbis virus-based therapies for ovarian cancer treatment holds great promise and warrants further investigation. Investigations using other oncolytic viruses in preclinical studies and clinical trials are also presented.
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Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias Ovarianas , Vacinas , Humanos , Feminino , Sindbis virus , Terapia Viral Oncolítica/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Imunoterapia/métodosRESUMO
The Liaison Committee on Medical Education (LCME) requires that well-being programs must be "effective." Yet most medical schools do not robustly assess their well-being programs. Most evaluate their programs using one question on the Association of American Medical College's annual Graduation Questionnaire (AAMC GQ) survey for fourth-year students on their satisfaction with well-being programs, which is inadequate and nonspecific and only assesses a specific time in training. In this perspective, we, as members of the AAMC Group on Student Affairs (GSA) - Committee on Student Affairs (COSA) Working Group on Medical Student Well-being, suggest adapting Kern's 6-step approach to curriculum development as an effective framework to guide the development and evaluation of well-being programs. We suggest strategies for applying Kern's steps to well-being programs, with attention to conducting needs assessments, identifying goals, implementation, and evaluation and feedback. While each institution will have unique goals emerging from their needs assessment, we put forth five common medical student well-being goals as examples. Applying a rigorous and structured approach to developing and evaluating undergraduate medical education well-being programs will involve defining a guiding philosophy and clear goals and implementing a strong assessment strategy. This Kern-based framework can help schools meaningfully assess the impact of their initiatives on student well-being.
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Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Humanos , Currículo , Faculdades de MedicinaRESUMO
Sindbis alphavirus vectors offer a promising platform for cancer therapy, serving as valuable models for alphavirus-based treatment. This review emphasizes key studies that support the targeted delivery of Sindbis vectors to tumor cells, highlighting their effectiveness in expressing tumor-associated antigens and immunomodulating proteins. Among the various alphavirus vectors developed for cancer therapy, Sindbis-vector-based imaging studies have been particularly extensive. Imaging modalities that enable the in vivo localization of Sindbis vectors within lymph nodes and tumors are discussed. The correlation between laminin receptor expression, tumorigenesis, and Sindbis virus infection is examined. Additionally, we present alternative entry receptors for Sindbis and related alphaviruses, such as Semliki Forest virus and Venezuelan equine encephalitis virus. The review also discusses cancer treatments that are based on the alphavirus vector expression of anti-tumor agents, including tumor-associated antigens, cytokines, checkpoint inhibitors, and costimulatory immune molecules.
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Alphavirus , Vírus da Encefalite Equina Venezuelana , Neoplasias , Humanos , Alphavirus/genética , Vetores Genéticos/genética , Neoplasias/terapia , Terapia Genética/métodosRESUMO
For medical students first entering the clinical space in July 2020, the unique challenges related to the coronavirus pandemic threatened to amplify the psychological distress associated with clerkship rotations. This study aimed to characterize the mental health of third-year medical students starting clinical clerkships in the midst of a pandemic by assessing symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) as well as risk, coping, and protective factors associated with psychological outcomes. Of 147 third-year medical students at the Icahn School of Medicine at Mount Sinai in New York City, 110 (75%) participated in this prospective survey-based study with 108 included in the final analysis. 43 (39.8%) respondents screened positive for symptoms of either MDD, GAD, or PTSD. Multiple regression analyses revealed that greater overall symptom severity was associated with more avoidant coping, more traumatic events witnessed, poorer student and leisure functioning, lower trait emotional stability, and lower social support. Worries related to COVID-19 did not significantly influence outcome variables. To better understand the role of the pandemic on psychological outcomes in third-year medical students, additional research should focus on the trajectory of these outcomes over the year during the coronavirus pandemic.
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COVID-19 , Estágio Clínico , Transtorno Depressivo Maior , Estudantes de Medicina , Depressão/psicologia , Humanos , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Estudantes de Medicina/psicologiaRESUMO
INTRODUCTION: Little is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID-19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID-19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID-19-related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties. METHOD: Data were collected in spring 2020, through an anonymous survey delivered to a purposively-selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID-19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample. RESULTS: The majority of the sample (52.7%-87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID-19 moral distress: negative impact on family, fear of infecting others, and work-related concerns. All three factors were significantly associated with severity and positive screen for COVID-19-related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes. CONCLUSION: Moral distress is prevalent in FHCWs and includes family-, infection-, and work-related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.
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Esgotamento Profissional , COVID-19 , Transtornos de Estresse Pós-Traumáticos , Esgotamento Profissional/epidemiologia , Pessoal de Saúde , Humanos , Princípios Morais , Pandemias , Funcionamento Psicossocial , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical trials rarely include EAC. This work sought to compare clinical characteristics and treatment outcomes of advanced EAC with those of GEJ-AC and GAC and examine prognostic factors. PATIENTS AND METHODS: Participants comprised patients with advanced EAC, intestinal GEJ-AC, and GAC treated with platin and fluoropyrimidine (plus trastuzumab when HER2 status was positive). Overall and progression-free survival were estimated using the Kaplan-Meier method. Cox proportional hazards regression gauged the prognostic value of the AGAMENON model. RESULTS: Between 2008 and 2019, 971 participants from the AGAMENON-SEOM registry were recruited at 35 centers. The sample included 67.3% GAC, 13.3% GEJ-AC, and 19.4% EAC. Pulmonary metastases were most common in EAC and peritoneal metastases in GAC. Median PFS and OS were 7.7 (95% CI 7.3-8.0) and 13.9 months (12.9-14.7). There was no difference in PFS or OS between HER2- and HER2+ tumors from the three locations (p > 0.05). Five covariates were found to be prognostic for the entire sample: ECOG-PS, histological grade, number of metastatic sites, NLR, and HER2+ tumors treated with trastuzumab. In EAC, the same variables were prognostic except for grade. The favorable prognosis for HER2+ cancers treated with trastuzumab was homogenous for all three subgroups (p = 0.351) and, after adjusting for the remaining covariates, no evidence supported primary tumor localization as a prognostic factor (p = 0.331). CONCLUSION: Our study supports the hypothesis that EAC exhibits clinicopathological characteristics, prognostic factors, and treatment outcomes comparable to intestinal GEJ-AC and GAC.
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Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Feminino , Humanos , Intestinos/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Receptor ErbB-2/metabolismo , Sistema de Registros , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Trastuzumab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Docetaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico , Vigilância de Produtos Comercializados , Intervalo Livre de Progressão , Estudos Prospectivos , Pirimidinas/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17â¼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106bâ¼25, that is expressed in the same cells, were reported to have no effect on testis development and function. The aim of this work is to determine the role of these two miRNA clusters in spermatogenesis and male fertility. For this, we analyzed miR-106bâ¼25 and miR-17â¼92 single and double mouse mutants and compared them to control mice. We found that miR-106bâ¼25 knock out testes show reduced size, oligozoospermia and altered spermatogenesis. Transcriptomic analysis showed that multiple molecular pathways are deregulated in these mutant testes. Nevertheless, mutant males conserved normal fertility even when early spermatogenesis and other functions were disrupted. In contrast, miR-17â¼92+/-; miR-106bâ¼25-/- double mutants showed severely disrupted testicular histology and significantly reduced fertility. Our results indicate that miR-106bâ¼25 and miR-17â¼92 ensure accurate gene expression levels in the adult testis, keeping them within the required thresholds. They play a crucial role in testis homeostasis and are required to maintain male fertility. Hence, we have identified new candidate genetic factors to be screened in the molecular diagnosis of human males with reproductive disorders. Finally, considering the well-known oncogenic nature of these two clusters and the fact that patients with reduced fertility are more prone to testicular cancer, our results might also help to elucidate the molecular mechanisms linking both pathologies.
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MicroRNAs/metabolismo , Oligospermia/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Camundongos , MicroRNAs/genética , Oligospermia/genética , Espermatogênese/genética , Espermatogênese/fisiologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismoRESUMO
Childhood sexual abuse (CSA), a global public health problem, is often underreported especially in low-income countries such as El Salvador, and prevention efforts are needed. The purpose of this study was to examine knowledge, attitudes and experiences of CSA prevention and characteristics related to greater knowledge and openness to engaging in child abuse prevention among Salvadoran parents. Salvadoran parents (N = 478) completed questionnaires regarding demographics, definition and signs and symptoms of child abuse, personal experiences of CSA, CSA prevention training, and knowledge, attitudes and practices about preventing CSA. Most parents were knowledgeable about CSA, viewed CSA prevention as their responsibility, and had talked with their children about CSA, although 65.7% incorrectly believed that children are more likely to be abused by strangers. Parents with lower income were less knowledgeable and willing to participate in CSA prevention. CSA programing needs to involve parents and specifically target low-income parents.
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Abuso Sexual na Infância/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Pais , Pobreza , Adulto , Criança , El Salvador , Feminino , Humanos , MasculinoAssuntos
COVID-19 , Educação de Graduação em Medicina , Currículo , Humanos , Pandemias , SARS-CoV-2RESUMO
The 37-kDa laminin receptor (37LRP or RPSA) is a remarkable, multifaceted protein that functions in processes ranging from matrix adhesion to ribosome biogenesis. Its ability to engage extracellular laminin is further thought to contribute to cellular migration and invasion. Most commonly associated with metastatic cancer, RPSA is also increasingly found to be important in other pathologies, including microbial infection, neurodegenerative disease and developmental malformations. Importantly, it is thought to have higher molecular weight forms, including a 67-kDa species (67LR), the expression of which is linked to strong laminin binding and metastatic behavior. The composition of these larger forms has remained elusive and controversial. Homo- and heterodimerization have been proposed as events capable of building the larger species from the monomeric 37-kDa precursor, but solid evidence is lacking. Here, we present data suggesting that higher molecular weight species require SUMOylation to form. We also comment on the difficulty of isolating larger RPSA species for unambiguous identification and demonstrate that cell lines stably expressing tagged RPSA for long periods of time fail to produce tagged higher molecular weight RPSA. It is possible that higher molecular weight species like 67LR are not derived from RPSA.
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Receptores de Laminina/química , Receptores de Laminina/metabolismo , Proteínas Ribossômicas/química , Proteínas Ribossômicas/metabolismo , Animais , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Imunoprecipitação , Camundongos , Peso Molecular , Células NIH 3T3 , Receptores de Laminina/genética , Proteínas Ribossômicas/genética , Sumoilação , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
An evaluation of the impact of osteoporosis on loss of spinal stability, with or without intervertebral disc degeneration, using computational analysis is presented. The research also investigates the correlation between osteoporosis and intervertebral disc degeneration. Three-dimensional finite element models of human lumbar spine segments were used to assess the influence of osteoporosis on spinal stability. Five different models of age-related degeneration were created using various material properties for trabecular bone and intervertebral discs. Calculation results indicate that in a spine with osteoporosis, the deformation of the intervertebral discs can increase by more than 30% when compared to a healthy spine. Thus, intervertebral disc deformation depends not only on the degree of degeneration of the discs themselves, but their deformation is also influenced by the degree of osteoporosis of the vertebrae. Additionally, the load-bearing capacity of the spine can decrease by up to 30% with osteoporosis, regardless of the degree of intervertebral disc deformation. In conclusion, osteoporosis can contribute to intervertebral disc degeneration.
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ABSTRACT: Most medical schools have instituted undergraduate medical education (UME) well-being programs in recent years in response to high rates of medical student distress, but there is currently significant variability in the structure of UME well-being programs and limited guidance on how to best structure such programs to achieve success. In this article, the authors, all leaders of medical student well-being programs at their home institutions and members of the Association of American Medical Colleges Group on Student Affairs Committee on Student Affairs Working Group on Medical Student Well-Being between 2019 and 2023 offer guidance to the national community on how best to structure a UME well-being program. They use the current literature and their professional experiences leading well-being efforts at 7 different institutions to review the case for addressing medical student well-being, propose a guiding model, and make recommendations for strategies to implement this model.The proposed guiding model emphasizes the importance of the learning environment and efficiency of learning to medical student well-being, as well as personal resilience. Based on this model, the authors recommend specific and tangible well-being strategies to implement systemic interventions to improve the learning environment, efficiency of learning, and personal resilience, including formalizing the well-being program; hiring qualified, dedicated, and empowered well-being leadership with clear responsibilities; acting as a central hub for resources and as a liaison with mental health care; and establishing robust program evaluation methods.
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Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Educação de Graduação em Medicina/métodos , Educação de Graduação em Medicina/organização & administração , Estudantes de Medicina/psicologia , Estados Unidos , Currículo , Saúde Mental , Resiliência Psicológica , Faculdades de Medicina/organização & administraçãoRESUMO
Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvement of non-coding regulation in this process remains unclear. Here we show that the deletion of a single microRNA cluster, miR-17~92, induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayed in XY knockout gonads, which develop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.
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Diferenciação Celular , MicroRNAs , Ovário , Células de Sertoli , Processos de Determinação Sexual , Proteína da Região Y Determinante do Sexo , Testículo , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Masculino , Células de Sertoli/metabolismo , Células de Sertoli/citologia , Camundongos , Ovário/metabolismo , Testículo/metabolismo , Proteína da Região Y Determinante do Sexo/genética , Proteína da Região Y Determinante do Sexo/metabolismo , Diferenciação Celular/genética , Processos de Determinação Sexual/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos Knockout , Diferenciação Sexual/genética , Transtornos do Desenvolvimento Sexual/genética , Gônadas/metabolismoRESUMO
This study investigated third year medical students' psychological well-being during clinical rotations at Mount Sinai hospitals in New York City during the COVID-19 pandemic. All students (n = 147) starting rotations (psychiatry, surgery, obstetrics-gynecology, neurology, pediatrics, and medicine) could participate in quarterly, online, anonymous surveys comprised of validated screeners for: psychological symptoms, risk, coping, and protective factors, demographics, COVID-19 worries, and stressful clerkship-related events. Associations between variables were examined with Chi-squared, Fisher's exact, t-, Wilcoxon Rank Sum, one-way ANOVA, and McNemar tests. Significant univariate predictors of psychological distress were included in stepwise multivariable linear regression models. The baseline survey was completed by 110 (74.8%) students; ninety-two (62.6%) completed at least one other survey. During the year, 68 (73.9%) students screened positive for depression, anxiety, or PTSD. The prevalence of psychiatric symptoms peaked in June 2020 without significant changes in average scores over time. COVID-19 worries decreased over time but did not influence psychological symptoms at year-end. Eighty-three students (90.2%) experienced stressful clerkship-related events, which were traumatic and/or COVID-19-related for 26 (28.3%) and 22 students (24.0%), respectively. Baseline psychological distress, childhood emotional abuse, and resilience predicted depression, anxiety, and/or PTSD by year-end. This study highlights the importance of recognizing psychological distress and implementing interventions to support students' well-being.
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COVID-19 , Estudantes de Medicina , Humanos , Criança , COVID-19/epidemiologia , Estudantes de Medicina/psicologia , Pandemias , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Hospitais , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Low- or very-low-pressure hydrocephalus is a serious and rare phenomenon, which is becoming better known since it was first described in 1994 by Pang and Altschuler. Forced drainage at negative pressures can, in most cases, restore the ventricles to their original size, thus achieving neurological recovery. We present six new cases that suffered this syndrome from 2015 to 2020: two of them after medulloblastoma surgery; a third one as a consequence of a severe head trauma that required bifrontal craniectomy; another one after craniopharyngioma surgery; a fifth one with leptomeningeal glioneuronal tumor; and, finally, a patient with a shunt for normotensive hydrocephalus. Before the development of this condition, four of them had mid-low-pressure cerebrospinal fluid (CSF) shunts. Four patients required cerebrospinal fluid (CSF) drainage at negative pressures oscillating from zero to -15 mmHg by external ventricular drainage until ventricular size normalized, followed by the placement of a new definitive low-pressure shunt, one of them to the right atrium. The duration of drainage in negative pressures through external ventricular drainage (EVD) ranged from 10 to 40 days with concomitant intracranial pressure monitoring at the neurointensive care unit. Approximately 200 cases of this syndrome have been described in the literature. The causes are varied and superimposable to those of high-pressure hydrocephalus. Neurological impairment is due to ventricular size and not to pressure values. Subzero drainage is still the most commonly used method, but other treatments have been described, such as neck wrapping, ventriculostomy of the third ventricle, and lumbar blood patches when associated with lumbar puncture. Its pathophysiology is not clear, although it seems to involve changes in the permeability and viscoelasticity of the brain parenchyma together with an imbalance in CSF circulation in the craniospinal subarachnoid space.
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OBJECTIVE: To examine racial/ethnic differences in mental health outcomes and risk factors during the COVID-19 pandemic among frontline healthcare workers (FHCWs). METHODS: A survey was conducted on FHCWs at a large metropolitan hospital during winter 2021. Depression, anxiety, and post-traumatic stress symptoms, demographic characteristics, and COVID-19-related occupational factors were assessed. Multivariable logistic regression examined factors associated with screening positive for psychiatric symptoms and their interactions with race/ethnicity. RESULTS: Of 1437 FHCWs, 762 (53.0%) self-identified as white, 451 (31.4%) as Asian, 118 (8.2%) as Black, and 106 (7.4%) as Latinx. Black FHCWs had a higher prevalence of screening positive for depression (18.6%) than other groups (6.6%-11.7%, p < .05). Significant risk factors by race/ethnicity interactions indicated that having cared for patients who died from COVID-19 increased risk of psychiatric symptoms among white and Black individuals, having to make difficult decisions prioritizing patients increased risk most significantly among white and Asian individuals, and working more hours increased risk most significantly among Latinx individuals. CONCLUSION: Results suggest that occupational stressors may have differential impacts on mental health among racial/ethnic groups of FHCWs. Findings provide insight on subgroups with increased vulnerability to certain risk factors and inform interventions to improve mental health in diverse FHCWs.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Pessoal de Saúde , Fatores de Risco , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Extensive research efforts in the field of brain tumor studies have led to the reclassification of tumors by the World Health Organization (WHO) and the identification of various molecular subtypes, aimed at enhancing diagnosis and treatment strategies. However, the quest for biomarkers that can provide a deeper understanding of tumor development mechanisms, particularly in the case of gliomas, remains imperative due to their persistently incurable nature. Oxidative stress has been widely recognized as a key mechanism contributing to the formation and progression of malignant tumors, with imbalances in antioxidant defense systems being one of the underlying causes for the excess production of reactive oxygen species (ROS) implicated in tumor initiation. In this study, we investigated the gene expression patterns of the eight known isoforms of glutathione peroxidase (GPx) in brain tissue obtained from male and female control rats, as well as rats with transplacental ethyl nitrosourea (ENU)-induced brain tumors. Employing the delta-delta Ct method for RT-PCR, we observed minimal expression levels of gpx2, gpx5, gpx6, and gpx7 in the brain tissue from the healthy control animals, while gpx3 and gpx8 exhibited moderate expression levels. Notably, gpx1 and gpx4 displayed the highest expression levels. Gender differences were not observed in the expression profiles of these isoforms in the control animals. Conversely, the tumor tissue exhibited elevated relative expression levels in all isoforms, except for gpx4, which remained unchanged, and gpx5, which exhibited alterations solely in female animals. Moreover, except for gpx1, which displayed no gender differences, the relative expression values of gpx2, gpx3, gpx6, gpx7, and gpx8 were significantly higher in the male animals compared to their female counterparts. Hence, the analysis of glutathione peroxidase isoforms may serve as a valuable approach for discerning the behavior of brain tumors in clinical settings.
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Neoplasias Encefálicas , Glioma , Animais , Feminino , Masculino , Ratos , Encéfalo , Neoplasias Encefálicas/genética , Glioma/genética , Glutationa Peroxidase/genética , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. METHODS: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. RESULTS: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. CONCLUSION: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). GOV IDENTIFIER: NCT01584297.