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3.
Med Educ Online ; 29(1): 2330250, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38566608

RESUMO

Artificial Intelligence (AI) holds immense potential for revolutionizing medical education and healthcare. Despite its proven benefits, the full integration of AI faces hurdles, with ethical concerns standing out as a key obstacle. Thus, educators should be equipped to address the ethical issues that arise and ensure the seamless integration and sustainability of AI-based interventions. This article presents twelve essential tips for addressing the major ethical concerns in the use of AI in medical education. These include emphasizing transparency, addressing bias, validating content, prioritizing data protection, obtaining informed consent, fostering collaboration, training educators, empowering students, regularly monitoring, establishing accountability, adhering to standard guidelines, and forming an ethics committee to address the issues that arise in the implementation of AI. By adhering to these tips, medical educators and other stakeholders can foster a responsible and ethical integration of AI in medical education, ensuring its long-term success and positive impact.


In the ever-evolving landscape of medical education, the integration of Artificial Intelligence (AI) stands out as a revolutionary innovation with the potential to reshape learning methodologies and advance healthcare practices.However, this transformative journey is impeded by ethical concerns that demand careful attention.This reflects a delicate balance that educators must strike between embracing innovation and ensuring responsible implementation.The twelve provided tips serve as a practical guide, highlighting the complexities involved in incorporating AI ethically.By following these guidelines, educators contribute to shaping a healthcare workforce that is not only technologically proficient but also ethically grounded.


Assuntos
Inteligência Artificial , Educação Médica , Humanos , Responsabilidade Social , Estudantes
4.
Fetal Pediatr Pathol ; 43(2): 94-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38200700

RESUMO

INTRODUCTION: Minimally invasive tissue sampling of the brain in newborns using the Bard Monopty needle helps to diagnose various neurological conditions by obtaining relevant brain cores. We designed a modified procedure to provide maximum diagnostic utility in brain tissue biopsies. METHOD: Twenty newborns underwent postmortem minimally invasive tissue sampling of the brain through the anterior fontanelle and posterior approach, using the engraved lines on the needle labeled from mark 0 to 13. The cores were correlated with conventional autopsy findings. RESULTS: Meninges were best obtained at marks 0 and 1 from the anterior fontanelle and mark 1 from posterior fontenelle in 85% of cases. Periventricular brain parenchyma was best obtained from mark 3 and mark 1 from anterior and posterior fontanel, respectively in 90% cases. The sampling success in obtaining brain cores was 100%. DISCUSSION: This modified technique increases the yield of meninges and brain tissue in newborns and aids in diagnosis.


Assuntos
Encéfalo , Agulhas , Humanos , Recém-Nascido , Biópsia , Autopsia/métodos
5.
Turk Patoloji Derg ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38265103

RESUMO

OBJECTIVE: The classification of renal tumors is expanding with the addition of new molecular entities in the 5th World Health Organization classification. Apart from this, the major updates in the definition of papillary renal cell carcinoma are that these tumors are no longer subtyped into type 1 and type 2. In oncocytic tumors, the new molecularly defined renal tumors, emerging and novel entities need to be considered in the diagnosis of oncocytic and chromophobe renal tumors. MATERIAL AND METHODS: This is a retrospective study to review and reclassify papillary, oncocytic, and chromophobe renal tumors based on the new WHO classification and correlate with clinical data, gross, microscopic features, and immunohistochemistry markers. RESULTS: A total of thirteen cases were reviewed and the tumor grade was changed for three out of four cases of papillary renal cell carcinoma and a single case was recategorized and graded. In nine cases of oncocytic and chromophobe renal tumors, the diagnoses were modified in 3 cases. CONCLUSION: Newly defined molecular renal tumors require advanced immunohistochemistry markers and molecular tests. This poses diagnostic challenges to pathologists practicing in low resource settings where molecular tests are not available.

6.
BMC Pregnancy Childbirth ; 23(1): 804, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990299

RESUMO

BACKGROUND: Postmortem examination is the gold standard for establishing the cause of death. Minimally Invasive Tissue Sampling (MITS) of organs is a novel approach that can be used as an alternative to postmortem examination. In this study, the community perceptions in two states in South India towards neonatal postmortem and the acceptance towards the MITS technique is studied. METHODS: In-depth interviews were conducted among the participants from Kerala and Karnataka to understand the perception towards postmortem and the acceptance of the novel MITS technique. The interviews were audio recorded, and a thematic analysis was done to identify the overarching themes and codes. RESULTS: The knowledge and attitude of participants on conventional and MITS postmortem techniques, reasons for refusal, and the need for raising awareness were identified in the study. Participants favored the MITS techniques as it was less disfiguring and less time-consuming. The major concerns for refusal of conventional postmortem were that the procedure was disfiguring, time-consuming, and caused emotional stress to the parents. CONCLUSIONS: Participants favored the MITS approach over conventional postmortem as it caused less disfigurement and was conducive to the religious practice of burial of the body.


Assuntos
Autopsia , Humanos , Recém-Nascido , Causas de Morte , Índia , Pais , Pesquisa Qualitativa , Percepção
7.
Asian J Psychiatr ; 89: 103770, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37812998

RESUMO

BACKGROUND: ChatGPT has emerged as the most advanced and rapidly developing large language chatbot system. With its immense potential ranging from answering a simple query to cracking highly competitive medical exams, ChatGPT continues to impress the scientists and researchers worldwide giving room for more discussions regarding its utility in various fields. One such field of attention is Psychiatry. With suboptimal diagnosis and treatment, assuring mental health and well-being is a challenge in many countries, particularly developing nations. To this regard, we conducted an evaluation to assess the performance of ChatGPT 3.5 in Psychiatry using clinical cases to provide evidence-based information regarding the implication of ChatGPT 3.5 in enhancing mental health and well-being. METHODS: ChatGPT 3.5 was used in this experimental study to initiate the conversations and collect responses to clinical vignettes in Psychiatry. Using 100 clinical case vignettes, the replies were assessed by expert faculties from the Department of Psychiatry. There were 100 different psychiatric illnesses represented in the cases. We recorded and assessed the initial ChatGPT 3.5 responses. The evaluation was conducted using the objective of questions that were put forth at the conclusion of the case, and the aim of the questions was divided into 10 categories. The grading was completed by taking the mean value of the scores provided by the evaluators. Graphs and tables were used to represent the grades. RESULTS: The evaluation report suggests that ChatGPT 3.5 fared extremely well in Psychiatry by receiving "Grade A" ratings in 61 out of 100 cases, "Grade B" ratings in 31, and "Grade C" ratings in 8. Majority of the queries were concerned with the management strategies, which were followed by diagnosis, differential diagnosis, assessment, investigation, counselling, clinical reasoning, ethical reasoning, prognosis, and request acceptance. ChatGPT 3.5 performed extremely well, especially in generating management strategies followed by diagnoses for different psychiatric conditions. There were no responses which were graded "D" indicating that there were no errors in the diagnosis or response for clinical care. Only a few discrepancies and additional details were missed in a few responses that received a "Grade C" CONCLUSION: It is evident from our study that ChatGPT 3.5 has appreciable knowledge and interpretation skills in Psychiatry. Thus, ChatGPT 3.5 undoubtedly has the potential to transform the field of Medicine and we emphasize its utility in Psychiatry through the finding of our study. However, for any AI model to be successful, assuring the reliability, validation of information, proper guidelines and implementation framework are necessary.


Assuntos
Transtornos Mentais , Psiquiatria , Humanos , Reprodutibilidade dos Testes , Diagnóstico Diferencial , Transtornos Mentais/diagnóstico , Transtornos Mentais/tratamento farmacológico , Comunicação
8.
Theranostics ; 13(7): 2241-2255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153730

RESUMO

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Vesículas Extracelulares , Animais , Ratos , Bevacizumab/uso terapêutico , Injeções Intravítreas , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Diabetes Mellitus/tratamento farmacológico
9.
Asian J Psychiatr ; 82: 103505, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36791611

RESUMO

The lack of accountability is considered to be a major cause of the crisis in health care in India. Physicians as key stakeholders in the health care delivery system have traditionally been accountable for health concerns at the doctor-patient interface. Following social and organizational dynamics, the interpretations of accountability have broadened and shifted in the recent literature, expanding accountability to the community, national and global levels and to social domains. The objective of this study is to provide a comprehensive framework of accountability in medical practice that can be used as a vehicle for further contextualized research and policy input. Through literature review, this paper is presented in two parts. First, a description of accountability of a physician inclusive of the social domains is extracted by posing three pertinent questions: who is accountable? accountability to whom? and accountability for what? which addresses the roles, relationships with other stakeholders and domains of accountability. Second, a framework of accountability of a physician is designed and presented to illustrate the professional and social domains. This study revealed a shift from individual physician's accountability to collective accountability involving multiple stakeholders through complex reciprocal and multi-layered mechanisms inclusive of the social dimensions. We propose a comprehensive framework of accountability of the physician to include the social domains that its multidimensional and integrative of all stakeholders. Furthermore, we discuss the utility of the framework in the Indian health care system and how this can facilitate further research in understanding the social dimensions of all stakeholders.


Assuntos
Médicos , Humanos , Índia , Relações Médico-Paciente , Responsabilidade Social
11.
Front Immunol ; 13: 875788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693779

RESUMO

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune systems. These discoveries fuel novel approaches for the treatment of several bone pathologies including osteoporosis. Bifidobacterium longum (BL) is a preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in an ovariectomy (ovx)-induced post-menopausal osteoporotic mouse model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Strikingly, BL-induced Bregs were found to be significantly more efficient in suppressing osteoclastogenesis and modulating Treg-Th17 cell balance with respect to control Bregs in vitro. Our in vivo µCT and bone mechanical strength data further confirm that BL supplementation significantly enhanced bone mass and bone strength, along with improving the bone microarchitecture in ovx mice. Remarkably, alterations in frequencies of CD19+CD1dhiCD5+IL-10+ Bregs, CD4+Foxp3+IL-10+ Tregs, and CD4+Rorγt+IL-17+ Th17 cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-γ and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-α) strongly support the immunomodulatory potential of BL. Altogether, our findings establish a novel osteo-protective and immunomodulatory potential of BL in augmenting bone health under osteoporotic conditions.


Assuntos
Linfócitos B Reguladores , Bifidobacterium longum , Animais , Citocinas , Feminino , Humanos , Interleucina-10 , Interleucina-17 , Camundongos , Osteogênese , Ovariectomia/efeitos adversos
13.
J Health Psychol ; 27(12): 2806-2819, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34963351

RESUMO

Although medical mistrust (MM) may be an impediment to public health interventions, no MM scale has been validated across countries and the assessment of MM has not been explored using item response theory, which allows generalisation beyond the sampled data. We aimed to determine the dimensionality of a brief MM measure across four countries through Mokken analysis and Graded Response Modelling. Analysis of 1468 participants from UK (n = 1179), Ireland (n = 191), India (n = 49) and Malaysia (n = 49) demonstrated that MM items formed a hierarchical, unidimensional measure, which is very informative about high levels of MM. Possible item reduction and scoring changes were also demonstrated. This study demonstrates that this brief MM measure is suitable for international studies as it is unidimensional across countries, cross cultural, and shows that minor adjustments will not impact on the assessment of MM when using these items.


Assuntos
Obtenção de Tecidos e Órgãos , Confiança , Humanos , Índia , Irlanda , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
Environ Sci Pollut Res Int ; 29(3): 4206-4218, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34405325

RESUMO

Graywater reuse is one of the important concepts in attaining water sustainability. A major challenge in this area is to realize various components present in graywater. The present study involves the identification of the chemical components of graywater collected from three different environments and to investigate the efficiency of removal of some of these chemical components using ultrafiltration membranes (polyelectrolyte multilayer (PEM) membranes). The chemical components were analyzed using liquid chromatography connected with quadrupole time-of-flight (UPLC-Q-ToF-MS). A number of micropollutants including surfactants and certain contaminants of emerging concern (CECs) were identified from these samples. Out of 16 compounds identified, 13 were surfactants and the remaining were caffeine, oxybenzone, and benzophenone. These surfactants are mostly the ingredients of various detergents. Low-pressure filtration studies of the collected samples were carried out utilizing chitosan/polyacrylic acid (CHI/PAA) multilayer membranes. A 5.5 bilayer membrane showed more than 95% rejection of the identified compounds in the selected samples and significant improvement in the water quality parameters. This demonstrates that the membrane used in this work is effective in the removal of various chemicals from graywater as well as enhancing the water quality.


Assuntos
Filtração , Poluentes Químicos da Água , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Tensoativos , Poluentes Químicos da Água/análise
15.
Clin Infect Dis ; 73(Suppl_5): S408-S414, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910168

RESUMO

BACKGROUND: Minimally invasive tissue sampling (MITS) of organs has been used as an alternative to complete diagnostic autopsy in countries where refusal for autopsy in newborns is common for sociocultural reasons. There is a paucity of literature regarding the diagnostic utility of MITS of the brain after death in neonates with neurological insults, especially in India. METHODS: This was a prospective, preliminary single-center tertiary care hospital study in India, focused specifically on MITS of the brain after neonatal death as a diagnostic tool to identify the various neurological insults. All neonatal deaths with neurological symptoms occurring within the first 30 days of life were enrolled, irrespective of the suspected clinical diagnosis. RESULTS: Sixteen neonates were enrolled after death for MITS of the brain, performed for diagnostic purposes, during the study period from February 2020 to March 2021. Their gestational ages ranged from 26 to 38 weeks. All neonates had either a history of seizures and/or respiratory distress or clinical evidence of sepsis and were on ventilator support. Histopathology in all 16 neonates showed evidence of anoxia, with or without reactive astrogliosis or microgliosis. In 5 neonates with cranial ultrasound evidence of brain hemorrhage, MITS of the brain showed intraventricular hemorrhage, subdural hemorrhage, or intraparenchymal white matter microhemorrhages. Premortem blood culture-proven sepsis was seen in 9 neonates. In all cases (100%), MITS had a good diagnostic yield and was useful to establish the neurological insult in the brain. CONCLUSIONS: MITS of the brain provides an accurate and adequate diagnosis and can be an alternative to complete diagnostic autopsy for establishing the cause of death due to neurological insults, especially in low-resource settings where obtaining consent for more invasive procedure is often challenging.


Assuntos
Unidades de Terapia Intensiva Neonatal , Autopsia/métodos , Causas de Morte , Humanos , Lactente , Recém-Nascido , Projetos Piloto , Estudos Prospectivos
16.
Cureus ; 13(3): e14158, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33936871

RESUMO

Objective Latina and African American breast cancer survivors (BCS) are affected by health disparities that have negatively impacted their health outcomes and quality of life more than other BCS. Examining the relationships among social support, culture, and well-being in underserved groups may help clarify critical factors that influence health disparities in cancer survivors. Methodology Ethnic salience (impact of ethnicity on identity), religious support, social support, and well-being were examined in African American and Latina breast cancer survivors using archival data. Participants included 320 breast cancer survivors (28% African American and 72% Latina) ranging from 26-89 years old and one to five years post breast cancer diagnosis. Results Ethnic salience was positively associated with well-being (p < .001). African American breast cancer survivors endorsed greater well-being, social support, religious support, and ethnic salience than Latinas (ps < .05). Religious support was associated with well-being even after controlling for the effects of general social support [ΔR 2 = .02, p = .005; F(5, 298) = 23.67]. Conclusion Ethnic salience and religious support are important factors in understanding health disparities and should inform survivorship care plans for underserved populations.

17.
Indian Pediatr ; 58(8): 741-744, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33772530

RESUMO

OBJECTIVE: To determine breastmilk sodium changes in the first 72 hours after birth and to correlate maternal and neonatal variables with maternal breastmilk sodium. METHODS: We enrolled 245 mothers and their exclusively breast-fed neonates in this prospective cohort study. Singleton, inborn babies of greater than 34 weeks gestation, who were exclusively breastfed for the first 72 hours were included. Babies who required neonatal intensive care unit (NICU) admission, top up feeds or discharged before 72 hours were excluded. Study outcomes were changes in breast milk sodium in the first 72 hours and association of high maternal breast milk sodium with various maternal and neonatal variables. RESULTS: Mean (SD) breastmilk sodium steadily declined over the first 72 hours [53.5 (19.2), 38.5 (19.0) and 22.2 (10.6) mmol/L at 24, 48, 72 hours, respectively]. Breastfeeding £8 times per 24 hours in the first three days was the only factor significantly associated with high breastmilk sodium (P=0.008). Maternal age, gravida, mode of delivery, significant neonatal weight loss, hypernatremia, neonatal morbidities like fever, irritability, lethargy and poor suck had no significant correlation with high breastmilk sodium. CONCLUSIONS: Breastmilk sodium shows a steady decline in the first 72 hours after delivery. Feeding ≤8 times per day is associated high breastmilk sodium at 72 hours of age.


Assuntos
Leite Humano , Sódio , Aleitamento Materno , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Prospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-30979026

RESUMO

Eliciting different attitudes with survey questionnaires may impact on intention to donate organs. Previous research used varying numbers of questionnaire items, or different modes of intervention delivery, when comparing groups. We aimed to determine whether intention to donate organs differed among groups exposed to different theoretical content, but similar questionnaire length, in different countries. We tested the effect of excluding affective attitudinal items on intention to donate, using constant item numbers in two modes of intervention delivery. Study 1: A multi-country, interviewer-led, cross-sectional randomized trial recruited 1007 participants, who completed questionnaires as per group assignment: including all affective attitude items, affective attitude items replaced, negatively-worded affective attitude items replaced. Study 2 recruited a UK-representative, cross-sectional sample of 616 participants using an online methodology, randomly assigned to the same conditions. Multilevel models assessed effects of group membership on outcomes: intention to donate (primary), taking a donor card, following a web-link (secondary). In study 1, intention to donate did not differ among groups. Study 2 found a small, significantly higher intention to donate in the negatively-worded affective attitudes replaced group. Combining data yielded no group differences. No differences were seen for secondary outcomes. Ancillary analyses suggest significant interviewer effects. Contrary to previous research, theoretical content may be less relevant than number or valence of questionnaire items, or form of intervention delivery, for increasing intention to donate organs.


Assuntos
Atitude , Intenção , Ensaios Clínicos Controlados Aleatórios como Assunto , Doadores de Tecidos/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários
19.
Am J Reprod Immunol ; 81(3): e13085, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30614113

RESUMO

BACKGROUND AND OBJECTIVE: The modulatory role of prolactin in autoimmune regulation is well established. Hyperprolactinemia is often associated with autoimmune disease like systemic lupus erythematosus and autoimmune thyroid diseases. The objective was to compare levels of direct and indirect autoimmune factors in different categories of hyperprolactinemia cases and predict the direction of association between hyperprolactinemia and autoimmune factors, if any. METHODS: A total of 102 hyperprolactinemia cases (>100 ng/mL serum prolactin level) were included along with 24 controls. Among 102 hyperprolactinemia cases, there were 36 idiopathic cases, 19 pituitary adenoma cases, 36 drug-induced cases, and 11 cases associated with other secondary/systemic diseases (chronic renal failure, chronic hepatic failure, etc). MEASUREMENTS: Direct autoimmune markers, IL-2, IFN-γ, IL-4, and IL-5, were measured in serum by ELISA. Indirect autoimmune markers, anti-TPO, anti-tg, anti-CCP, VDRL, platelet count, and aPTT, were measured as per laboratory-defined protocol. RESULTS: Serum levels of IL-4 and anti-TPO were significantly high in idiopathic hyperprolactinemia cases. Serum IL-4 levels were also significantly high in pituitary adenoma cases, drug-induced cases, and in cases with other secondary causes of hyperprolactinemia. Serum anti-TPO levels were also significantly high in drug-induced hyperprolactinemia cases. CONCLUSION: No significant difference in autoimmune factors is observed between macroprolactinemia and true hyperprolactinemia. Serum IL-4 and anti-TPO were high in all categories of hyperprolactinemia. This suggests a possible association of hyperprolactinemia with autoimmune conditions (high IL-4 and anti-TPO), mostly subclinical. Thus, hyperprolactinemia case with serum prolactin level >100 ng/mL may require long-term follow-up for the development of autoimmune disease in future.


Assuntos
Adenoma/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Hiperprolactinemia/imunologia , Interleucina-4/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Neoplasias Hipofisárias/imunologia , Adenoma/diagnóstico , Adulto , Formação de Anticorpos , Autoimunidade , Feminino , Humanos , Hiperprolactinemia/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Prolactina/sangue , Sensibilidade e Especificidade , Regulação para Cima , Adulto Jovem
20.
Clin Dysmorphol ; 28(1): 17-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30303820

RESUMO

Glycogen storage disease IV (GSD IV), caused by a defect in GBE1, is a clinically heterogeneous disorder. A classical hepatic form and a neuromuscular form have been described. The severe neuromuscular form presents as a fetal akinesia deformation sequence or a congenital subtype. We ascertained three unrelated families with fetuses/neonates who presented with fetal akinesia deformation sequence to our clinic for genetic counseling. We performed a detailed clinical evaluation, exome sequencing, and histopathology examination of two fetuses and two neonates from three unrelated families presenting with these perinatally lethal neuromuscular forms of GSD IV. Exome sequencing in the affected fetuses/neonates identified four novel pathogenic variants (c.1459G>T, c.144-1G>A, c.1680C>G, and c.1843G>C) in GBE1 (NM_000158). Histopathology examination of tissues from the affected fetuses/neonate was consistent with the diagnosis. Here, we add three more families with the severe perinatally lethal neuromuscular forms of GSD IV to the GBE1 mutation spectrum.


Assuntos
Artrogripose/enzimologia , Artrogripose/genética , Sistema da Enzima Desramificadora do Glicogênio/genética , Doença de Depósito de Glicogênio Tipo IV/enzimologia , Doença de Depósito de Glicogênio Tipo IV/genética , Mutação/genética , Doenças Neuromusculares/enzimologia , Doenças Neuromusculares/genética , Artrogripose/patologia , Sequência de Bases , Feminino , Feto/patologia , Doença de Depósito de Glicogênio Tipo IV/patologia , Humanos , Recém-Nascido , Masculino , Doenças Neuromusculares/patologia , Linhagem
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