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[PMID]:28455389
[Au] Autor:Schott JM
[Ti] Título:The neurology of ageing: what is normal?
[So] Source:Pract Neurol;17(3):172-182, 2017 Jun.
[Is] ISSN:1474-7766
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ageing is associated with changes in the nervous system with consequent alterations in some neurological examination findings: understanding what is 'normal' at different ages is essential when evaluating patients. In seminal papers published in 1931, Dr MacDonald Critchley summarised his observations and the prevailing evidence on the effects of ageing on, among others, sensation, reflexes, ocular function, olfaction, movement and cognition. In this review, these observations are re-evaluated in light of contemporary evidence. Factors influencing the measurement and interpretation of these clinical findings are then discussed, including reproducibility, the influence of comorbidities, secular trends, how 'normality' should best be defined, the problems of extrapolating group data to individuals and the influence of presymptomatic neurodegenerative disease states. The case is made that context is critical, and that combining life course data with detailed clinical and biomarker phenotyping is required to understand the determinants of normal neurological function associated with ageing.
[Mh] Termos MeSH primário: Envelhecimento/fisiologia
Doenças do Sistema Nervoso
Neurologia/métodos
[Mh] Termos MeSH secundário: Animais
História do Século XX
Seres Humanos
Doenças do Sistema Nervoso/diagnóstico
Doenças do Sistema Nervoso/história
Doenças do Sistema Nervoso/terapia
Neurologia/história
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE; PORTRAITS; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1136/practneurol-2016-001566


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[PMID]:28456012
[Au] Autor:Alizadeh A; Dyck SM; Kataria H; Shahriary GM; Nguyen DH; Santhosh KT; Karimi-Abdolrezaee S
[Ad] Endereço:Regenerative Medicine Program, Department of Physiology and Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
[Ti] Título:Neuregulin-1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury.
[So] Source:Glia;65(7):1152-1175, 2017 Jul.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically-relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg-1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin-10 and arginase-1 expression. We also found a decrease in proinflammatory factors including IL-1ß, TNF-α, matrix metalloproteinases (MMP-2 and 9) and nitric oxide after injury. In addition, Nrg-1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg-1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg-1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll-like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg-1 treatment with the therapeutic dosage of 1.5 µg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg-1 in acute SCI and suggest a positive immunomodulatory role for Nrg-1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso/tratamento farmacológico
Doenças do Sistema Nervoso/etiologia
Neuregulina-1/uso terapêutico
Neuroglia/fisiologia
Recuperação de Função Fisiológica/fisiologia
Traumatismos da Medula Espinal/complicações
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Arginase/metabolismo
Células Cultivadas
Meios de Cultivo Condicionados/farmacologia
Modelos Animais de Doenças
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/fisiologia
Proteína Glial Fibrilar Ácida/metabolismo
Interleucina-10/metabolismo
Lipopolissacarídeos/toxicidade
Locomoção/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Neuregulina-1/metabolismo
Neuregulina-1/farmacologia
Neuroglia/efeitos dos fármacos
Ratos
Recuperação de Função Fisiológica/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Traumatismos da Medula Espinal/patologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media, Conditioned); 0 (Glial Fibrillary Acidic Protein); 0 (Lipopolysaccharides); 0 (Neuregulin-1); 130068-27-8 (Interleukin-10); EC 3.5.3.1 (Arginase); EC 3.5.3.1 (arginase I, rat)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23150


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Registro de Ensaios Clínicos
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[PMID]:29226797
[Au] Autor:Neelapu SS; Locke FL; Bartlett NL; Lekakis LJ; Miklos DB; Jacobson CA; Braunschweig I; Oluwole OO; Siddiqi T; Lin Y; Timmerman JM; Stiff PJ; Friedberg JW; Flinn IW; Goy A; Hill BT; Smith MR; Deol A; Farooq U; McSweeney P; Munoz J; Avivi I; Castro JE; Westin JR; Chavez JC; Ghobadi A; Komanduri KV; Levy R; Jacobsen ED; Witzig TE; Reagan P; Bot A; Rossi J; Navale L; Jiang Y; Aycock J; Elias M; Chang D; Wiezorek J; Go WY
[Ad] Endereço:From the University of Texas M.D. Anderson Cancer Center, Houston (S.S.N., J.R.W.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (F.L.L., J.C.C.); Washington University and Siteman Cancer Center, St. Louis (N.L.B., A. Ghobadi); University of Miami, Miami (L.J.L., K.V.K.); Stanford
[Ti] Título:Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
[So] Source:N Engl J Med;377(26):2531-2544, 2017 12 28.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×10 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. RESULTS: Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. CONCLUSIONS: In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).
[Mh] Termos MeSH primário: Imunoterapia Adotiva
Linfoma Difuso de Grandes Células B/terapia
Receptores de Antígenos de Linfócitos T/uso terapêutico
Linfócitos T/transplante
[Mh] Termos MeSH secundário: Adulto
Idoso
Antígenos CD19
Biomarcadores/sangue
Intervalo Livre de Doença
Feminino
Seres Humanos
Interleucinas/sangue
Linfoma Difuso de Grandes Células B/mortalidade
Masculino
Meia-Idade
Doenças do Sistema Nervoso/induzido quimicamente
Neutropenia/induzido quimicamente
Receptores de Antígenos de Linfócitos T/sangue
Taxa de Sobrevida
Linfócitos T/imunologia
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (Biomarkers); 0 (Interleukins); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171212
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1707447


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[PMID]:29406641
[Au] Autor:Celia T; Freysteinson WW; Frye RE
[Ti] Título:Concurrent Medical Conditions in Autism Spectrum Disorders.
[So] Source:Pediatr Nurs;42(5):230-4, 2016 Sep-Oct.
[Is] ISSN:0097-9805
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long thought to be purely psychological in origin, current research lends credenceto the idea that autism has a medical basis. Patients with autism can be among themost challenging patients that a healthcare provider may care for. Often the presentingsymptoms of autism make these patients difficult to examine and may alsomask underlying concurrent conditions. This article reviews some of the more commonconditions found concurrently in the autistic population.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/complicações
Transtorno do Espectro Autista/diagnóstico
Gastroenteropatias/etiologia
Doenças do Sistema Imune/etnologia
Doenças do Sistema Nervoso/etiologia
Transtornos do Sono-Vigília/etiologia
[Mh] Termos MeSH secundário: Adolescente
Transtorno do Espectro Autista/epidemiologia
Transtorno do Espectro Autista/fisiopatologia
Criança
Pré-Escolar
Comorbidade
Feminino
Gastroenteropatias/epidemiologia
Gastroenteropatias/terapia
Seres Humanos
Doenças do Sistema Imune/epidemiologia
Doenças do Sistema Imune/terapia
Lactente
Masculino
Doenças do Sistema Nervoso/epidemiologia
Doenças do Sistema Nervoso/terapia
Transtornos do Sono-Vigília/epidemiologia
Transtornos do Sono-Vigília/terapia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:27778404
[Au] Autor:Menzel L; Kleber L; Friedrich C; Hummel R; Dangel L; Winter J; Schmitz K; Tegeder I; Schäfer MK
[Ad] Endereço:Department of Anesthesiology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
[Ti] Título:Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury.
[So] Source:Glia;65(2):278-292, 2017 02.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn ) 24 h and 5 days after experimental TBI. Grn mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was elevated in Grn mice as reflected by increased transcription of pro-inflammatory cytokines TNFα, IL-1ß, IL-6, and decreased transcription of the anti-inflammatory cytokine IL-10. However, numbers of Iba1 microglia/macrophages and immigrated CD45 leukocytes were similar at perilesional sites while determination of IgG extravasation suggested stronger impairment of blood brain barrier integrity in Grn compared to wild-type mice. Most strikingly, Grn mice displayed exaggerated astrogliosis 5 days after TBI as demonstrated by anti-GFAP immunohistochemistry and immunoblot. GFAP astrocytes at perilesional sites were immunolabelled for iNOS and TNFα suggesting that pro-inflammatory activation of astrocytes was attenuated by PGRN. Accordingly, recombinant PGRN (rPGRN) attenuated LPS- and cytokine-evoked iNOS and TNFα mRNA expression in cultured astrocytes. Moreover, intracerebroventricular administration of rPGRN immediately before trauma reduced brain damage and neurological deficits, and restored normal levels of cytokine transcription, axonal injury and astrogliosis 5 days after TBI in Grn mice. Our results show that endogenous and recombinant PGRN limit axonal injury and astrogliosis and suggest therapeutic potential of PGRN in TBI. GLIA 2017;65:278-292.
[Mh] Termos MeSH primário: Axônios/patologia
Lesões Encefálicas Traumáticas/complicações
Lesões Encefálicas Traumáticas/patologia
Gliose/etiologia
Gliose/prevenção & controle
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Astrócitos/efeitos dos fármacos
Astrócitos/patologia
Axônios/metabolismo
Barreira Hematoencefálica/patologia
Proteínas de Ligação ao Cálcio/metabolismo
Células Cultivadas
Citocinas/genética
Citocinas/metabolismo
Modelos Animais de Doenças
Expressão Gênica/efeitos dos fármacos
Expressão Gênica/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Gliose/patologia
Peptídeos e Proteínas de Sinalização Intercelular/genética
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Lipopolissacarídeos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteínas dos Microfilamentos/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Doenças do Sistema Nervoso/etiologia
Doenças do Sistema Nervoso/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Calcium-Binding Proteins); 0 (Cytokines); 0 (Grn protein, mouse); 0 (Intercellular Signaling Peptides and Proteins); 0 (Lipopolysaccharides); 0 (Microfilament Proteins); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23091


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[PMID]:29253878
[Au] Autor:Asam K; Staniszewski A; Zhang H; Melideo SL; Mazzeo A; Voronkov M; Huber KL; Pérez E; Stock M; Stock JB; Arancio O; Nicholls RE
[Ad] Endereço:Department of Pathology and Cell Biology, Columbia University, New York, NY, United States of America.
[Ti] Título:Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid.
[So] Source:PLoS One;12(12):e0189413, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Soluble forms of oligomeric beta-amyloid (Aß) are thought to play a central role in Alzheimer's disease (AD). Transgenic manipulation of methylation of the serine/threonine protein phosphatase, PP2A, was recently shown to alter the sensitivity of mice to AD-related impairments resulting from acute exposure to elevated levels of Aß. In addition, eicosanoyl-5-hydroxytryptamide (EHT), a naturally occurring component from coffee beans that modulates PP2A methylation, was shown to confer therapeutic benefits in rodent models of AD and Parkinson's disease. Here, we tested the hypothesis that EHT protects animals from the pathological effects of exposure to elevated levels of soluble oligomeric Aß. We treated mice with EHT-containing food at two different doses and assessed the sensitivity of these animals to Aß-induced behavioral and electrophysiological impairments. We found that EHT administration protected animals from Aß-induced cognitive impairments in both a radial-arm water maze and contextual fear conditioning task. We also found that both chronic and acute EHT administration prevented Aß-induced impairments in long-term potentiation. These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Peptídeos beta-Amiloides/química
Transtornos Cognitivos/prevenção & controle
Serotonina/análogos & derivados
[Mh] Termos MeSH secundário: Doença de Alzheimer/patologia
Animais
Café
Cognição/efeitos dos fármacos
Condicionamento (Psicologia)
Modelos Animais de Doenças
Eletrofisiologia
Medo
Feminino
Potenciação de Longa Duração
Masculino
Aprendizagem em Labirinto
Metilação
Camundongos
Camundongos Endogâmicos C57BL
Doenças do Sistema Nervoso/tratamento farmacológico
Doenças do Sistema Nervoso/patologia
Plasticidade Neuronal
Fosforilação
Serotonina/farmacologia
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Coffee); 0 (eicosanoyl-5-hydroxytryptamide); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189413


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[PMID]:29390531
[Au] Autor:Tu Y; Gao F
[Ad] Endereço:Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
[Ti] Título:Dexmedetomidine-based monitored conscious sedation combined local anesthesia for levator resection in a 10-year-old child with Marcus Gunn jaw-winking synkinesis: A case report.
[So] Source:Medicine (Baltimore);96(51):e9369, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Levator resection has become a routine procedure for patients with severe Marcus Gunn jaw-winking synkinesis (MGJWS). To optimize the surgical outcome, adult patients need to be kept awake, or easily aroused and responsive to verbal commands during the operation. However, levator resection is commonly performed under general anesthesia in pediatric patients. In the present case, we described a successful anesthetic protocol of conscious sedation with local anesthesia for levator resection in a child. PATIENT CONCERNS: A 10-year-old boy with MGJWS was admitted to our hospital and scheduled for levator resection. The patient was born through a normal delivery and had no previous history of allergy, no comorbidity, and no history of receiving anesthesia or operation. The laboratory tests of the patient were unremarkable. DIAGNOSES: The diagnosis of MGJWS was made by two experienced ophthalmologists. INTERVENTIONS: A 10-year-old boy with MGJWS was admitted to our hospital and scheduled for levator resection. The levator resection was performed under monitored conscious sedation with dexmedetomidine and local anesthesia. OUTCOMES: Patient with spontaneous breathing responded normally to verbal commands throughout the operation, and no adverse events occurred. The patient and ophthalmologist reported high satisfaction with anesthesia management. LESSONS: Dexmedetomidine-based monitored conscious sedation with local anesthesia is a feasible alternative to general anesthesia for levator resection in collaborative patients.
[Mh] Termos MeSH primário: Blefaroptose/diagnóstico
Blefaroptose/terapia
Dexmedetomidina/administração & dosagem
Cardiopatias Congênitas/diagnóstico
Cardiopatias Congênitas/terapia
Anormalidades Maxilomandibulares/diagnóstico
Anormalidades Maxilomandibulares/terapia
Monitorização Fisiológica/métodos
Doenças do Sistema Nervoso/diagnóstico
Doenças do Sistema Nervoso/terapia
Músculos Oculomotores/cirurgia
[Mh] Termos MeSH secundário: Anestesia Local
Criança
Sedação Consciente/métodos
Seguimentos
Seres Humanos
Masculino
Doenças Raras
Reflexo Anormal
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
67VB76HONO (Dexmedetomidine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009369


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[PMID]:28450582
[Au] Autor:McConnell MJ; Moran JV; Abyzov A; Akbarian S; Bae T; Cortes-Ciriano I; Erwin JA; Fasching L; Flasch DA; Freed D; Ganz J; Jaffe AE; Kwan KY; Kwon M; Lodato MA; Mills RE; Paquola ACM; Rodin RE; Rosenbluh C; Sestan N; Sherman MA; Shin JH; Song S; Straub RE; Thorpe J; Weinberger DR; Urban AE; Zhou B; Gage FH; Lehner T; Senthil G; Walsh CA; Chess A; Courchesne E; Gleeson JG; Kidd JM; Park PJ; Pevsner J; Vaccarino FM; Brain Somatic Mosaicism Network
[Ti] Título:Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.
[So] Source:Science;356(6336), 2017 Apr 28.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders.
[Mh] Termos MeSH primário: Encéfalo/anormalidades
Transtornos Mentais/genética
Mosaicismo
Doenças do Sistema Nervoso/genética
Células-Tronco Neurais/fisiologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Encéfalo/metabolismo
Divisão Celular/genética
Dano ao DNA
Análise Mutacional de DNA/métodos
Reparo do DNA/genética
Replicação do DNA
Genoma Humano
Células Germinativas/metabolismo
Seres Humanos
Rede Nervosa/crescimento & desenvolvimento
Rede Nervosa/metabolismo
Células-Tronco Neurais/metabolismo
Neurônios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  9 / 37050 MEDLINE  
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[PMID]:29304053
[Au] Autor:Kelly KA; Michalovicz LT; Miller JV; Castranova V; Miller DB; O'Callaghan JP
[Ad] Endereço:Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, West Virginia.
[Ti] Título:Prior exposure to corticosterone markedly enhances and prolongs the neuroinflammatory response to systemic challenge with LPS.
[So] Source:PLoS One;13(1):e0190546, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflammatory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to interact with and alter neuroinflammatory responses and associated behaviors. Here, we examined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a single injection (2mg/kg, s.c.) or inhalation exposure (7.5 µg/m3) of LPS or polyinosinic:polycytidylic acid (PIC; 12mg/kg, i.p.) in adult male C57BL/6J mice. CORT was given in the drinking water (200 mg/L) for 1 week or every other week for 90 days followed by LPS. Proinflammatory cytokine expression (TNFα, IL-6, CCL2, IL-1ß, LIF, and OSM) was measured by qPCR. The activation of the neuroinflammation downstream signaling activator, STAT3, was assessed by immunoblot of pSTAT3Tyr705. The presence of astrogliosis was assessed by immunoassay of GFAP. Acute exposure to LPS caused brain-wide neuroinflammation without producing astrogliosis; exposure to CORT for 1 week caused marked exacerbation of the LPS-induced neuroinflammation. This neuroinflammatory "priming" by CORT was so pronounced that sub-neuroinflammatory exposures by inhalation instigated neuroinflammation when paired with prior CORT exposure. This effect also was extended to another common inflammagen, PIC (a viral mimic). Furthermore, a single week of CORT exposure maintained the potential for priming for 30 days, while intermittent exposure to CORT for up to 90 days synergistically primed the LPS-induced neuroinflammatory response. These findings highlight the possibility for an isolated inflammatory event to be exacerbated by a temporally distant stressful stimulus and demonstrates the potential for recurrent stress to greatly aggravate chronic inflammatory disorders.
[Mh] Termos MeSH primário: Corticosterona/administração & dosagem
Inflamação/induzido quimicamente
Lipopolissacarídeos/administração & dosagem
Doenças do Sistema Nervoso/induzido quimicamente
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Lipopolysaccharides); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190546


  10 / 37050 MEDLINE  
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[PMID]:29419692
[Au] Autor:Mohamadi A; Googanian A; Ahmadi A; Kamali A
[Ad] Endereço:Department of Neurosurgery.
[Ti] Título:Comparison of surgical or nonsurgical treatment outcomes in patients with thoracolumbar fracture with Score 4 of TLICS: A randomized, single-blind, and single-central clinical trial.
[So] Source:Medicine (Baltimore);97(6):e9842, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Thoracolumbar fractures are among the most common types of damages caused to the spinal cord .Therefore, the aim of this study was the comparison of surgical or nonsurgical treatment outcomes in patients with thoracolumbar fracture with score 4 of the thoracolumbar injury classification and severity (TLICS) METHODS:: This study was clinical trial and double blind. Patients with thoracolumbar fracture with score 4 of TLICS entered at this research. We divided patients in 2 groups randomly (each group 25 patients) and then we followed patients for 1 year after start of treatment. We checked duration of bedridden and absence work, pain every 3 months for 1 year and radiography every 3 months for 1 year. RESULTS: Pain in operative group was lower than nonoperative group (P = .02). Regional sagittal angles (RSA) in operative group was lower than nonoperative group in all time (P = .0001). Mean of time of return to work in operative group was lower than nonoperative group (P = .001). CONCLUSIONS: Pain and mean of time of return to work and RSA in operative group was lower than nonoperative group. The present data suggest the use of operative method in patients with thoracolumbar fracture with score 4 of TLICS.
[Mh] Termos MeSH primário: Tratamento Conservador
Vértebras Lombares
Traumatismos da Medula Espinal/cirurgia
Fraturas da Coluna Vertebral/cirurgia
Procedimentos Cirúrgicos Operatórios
Vértebras Torácicas
[Mh] Termos MeSH secundário: Adulto
Tratamento Conservador/efeitos adversos
Tratamento Conservador/métodos
Feminino
Seres Humanos
Vértebras Lombares/lesões
Vértebras Lombares/cirurgia
Masculino
Doenças do Sistema Nervoso/diagnóstico
Doenças do Sistema Nervoso/etiologia
Avaliação de Resultados da Assistência ao Paciente
Procedimentos Cirúrgicos Operatórios/efeitos adversos
Procedimentos Cirúrgicos Operatórios/métodos
Vértebras Torácicas/lesões
Vértebras Torácicas/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009842



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