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1.
World Neurosurg ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014543

RESUMO

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The pre-residency publication volume of US neurosurgery interns and any potential association between applicant publication volume and the match results of top ranked residency programs has not been well-characterized. OBJECTIVE: In this study, we sought to characterize the pre-residency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Pre-residency publication volumes of interns at the top 25 programs (based on a composite ranking score according to four different ranking metrics) were compared to those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least one publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± SEM). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs 5.7 ± 0.8, P = 0.0267) compared to interns at all other programs. CONCLUSION: Our results provide a general estimate of the pre-residency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching into top-25 neurosurgery residency programs.

2.
Transl Neurosci ; 10: 233-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497319

RESUMO

Timely dissemination of results from clinical studies is crucial for the advancement of knowledge and clinical decision making. A large body of research has shown that up to half of clinical trials do not publish their findings. In this study, we sought to determine whether clinical trial publication rates within neurology have increased over time. Focusing on neurology clinical trials completed between 2008 to 2014, we found that while the overall percentage of published trials has not changed (remaining at approximately 50%), time to publication has significantly decreased. Our findings suggest that clinical trials within neurology are being published in a more timely manner.

3.
Theranostics ; 9(17): 4959-4970, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410194

RESUMO

The strongest genetic risk factor for Alzheimer's disease (AD) is the Apolipoprotein E type 4 allele (ApoE ε4). The interaction between sex and ApoE ε4 carrier status on AD risk remains an area of intense investigation. We hypothesized that sex modulates the relationship between ApoE ε4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI). Methods: Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between 18F-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed. Results: After applying PVC and controlling for age, education level and global cortical 18F-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE ε4 by sex interaction effect (false discovery rate P < 0.1) among MCI individuals. We also found a significant ApoE ε4 by sex interaction effect on CSF t-tau and p-tau. 18F-AV-1451 SUVR in the 5 ROIs with ApoE ε4 by sex interaction was significantly correlated with CSF p-tau and t-tau. Conclusions: Our findings suggest that women are more susceptible to ApoE ε4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE ε4 by sex effects on brain tau deposition in MCI participants.

4.
Transl Neurosci ; 10: 195-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410303

RESUMO

Objective: To describe and assess the educational value of a functional neurosurgery clinical shadowing and research tutorial for pre-medical trainees. Design: Program participants observed functional neurosurgery procedures and conducted basic science and clinical research in neurosurgery fields. Former participants completed a brief online survey to evaluate their perspectives and experiences throughout the tutorial. Setting: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Participants: 15 pre-medical and post-baccalaureate trainees participated in the tutorial. All former tutorial participants were emailed. Results: 11/15 former participants responded to the survey. Survey results suggest that the tutorial program increased participants' understanding of and interest in neurosurgery and related fields in neuroscience. Conclusions: The functional neurosurgery medical tutorial provides valuable clinical and research exposure in neurosurgery fields for pre-medical trainees. Our work is a preliminary step in addressing the crucial challenge of training the next generation of neurosurgeon-scientists by providing a pedagogical paradigm for development of formal experiences that integrate original scientific research with clinical neurosurgery exposure.

5.
Nat Commun ; 10(1): 3902, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467281

RESUMO

Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. Here, we aim to identify SLE subgroups within a multiethnic cohort using an unsupervised clustering approach based on the American College of Rheumatology (ACR) classification criteria. We identify three patient clusters that vary according to disease severity. Methylation association analysis identifies a set of 256 differentially methylated CpGs across clusters, including 101 CpGs in genes in the Type I Interferon pathway, and we validate these associations in an external cohort. A cis-methylation quantitative trait loci analysis identifies 744 significant CpG-SNP pairs. The methylation signature is enriched for ethnic-associated CpGs suggesting that genetic and non-genetic factors may drive outcomes and ethnic-associated methylation differences. Our computational approach highlights molecular differences associated with clusters rather than single outcome measures. This work demonstrates the utility of applying integrative methods to address clinical heterogeneity in multifactorial multi-ethnic disease settings.


Assuntos
Biologia Computacional , Grupos Étnicos/genética , Genômica , Lúpus Eritematoso Sistêmico/genética , Família Multigênica , Estudos de Coortes , Metilação de DNA , Epigenômica , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Locos de Características Quantitativas , Índice de Gravidade de Doença , Estados Unidos
6.
Trends Pharmacol Sci ; 40(8): 565-576, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326236

RESUMO

Computational drug repurposing has the ability to remarkably reduce drug development time and cost in an era where these factors are prohibitively high. Several examples of successful repurposed drugs exist in fields such as oncology, diabetes, leprosy, inflammatory bowel disease, among others, however computational drug repurposing in neurodegenerative disease has presented several unique challenges stemming from the lack of validation methods and difficulty in studying heterogenous diseases of aging. Here, we examine existing approaches to computational drug repurposing, including molecular, clinical, and biophysical methods, and propose data sources and methods to advance computational drug repurposing in neurodegenerative disease using Alzheimer's disease as an example.

7.
Neuroimage Clin ; 22: 101795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991617

RESUMO

While the ApoE ε4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24 ApoE ε4 carriers and 24 age-matched ApoE ε4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in ApoE carriers and non-carriers separately. Results with PVC were compared with ones from non-PVC based analysis. After applying PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in ApoE ε4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the PVC based analysis, fewer significant ApoE-associated regions and clusters were found in the non-PVC based PET analysis. Our findings suggest that the ApoE ε4 genotype is associated with a longitudinal decline in glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel ApoE ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification.


Assuntos
Apolipoproteína E4/genética , Apolipoproteínas E/genética , Encéfalo/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Glucose/metabolismo , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
8.
J Dermatol Sci ; 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29903654

RESUMO

BACKGROUND: Allergic contact dermatitis (ACD) is a highly prevalent inflammatory disease of the skin. As a result of the complex etiology in ACD, therapeutic compounds targeting refractory pruritus in ACD lack efficacy and lead to numerous side effects. OBJECTIVE: In this study, we investigated the anti-pruritic effects of oxymatrine (OMT) and explored its mechanism of action in a mouse model of ACD. METHOD: 72 male SPF C57BL/6 mice were randomly divided into control group, ACD model group, dexamethasone positive control group (0.08 mg kg-1) and 3 OMT groups (80, 40, 20 mg kg-1). OMT was administrated by intraperitoneal injection 1 h before video recording on day 10, 24 h after 2nd challenge with SADBE. Cheek skin fold thickness was measured before treatment and after recording. H&E staining was used for pathological observation. RT-qPCR, Immunohistochemistry and LEGENDplexTM assay were used to detect cytokines levels. The population of Treg cells in peripheral blood were detected via flow cytometry. RESULTS: OMT treatment significantly decreases the skin inflammation and scratching bouts. It rescues defects in epidermal keratinization and inflammatory cell infiltration in ACD mice. Administration of OMT significantly reduced levels of IFN-γ, IL-13, IL-17A, TNF-α, IL-22 and mRNA expression of TNF-α and IL-1ß. Furthermore, it increased the percentage of Treg cells in peripheral blood of ACD mice. CONCLUSION: We have demonstrated that OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators. OMT might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD.

9.
J Ethnopharmacol ; 195: 118-126, 2017 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-27880884

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Angong Niuhuang Pill (ANP) is a well known Chinese traditional therapeutic for the treatment for diseases affecting the Central Nervous System (CNS). Components of the ANP formulation, including Bovis Calculus Sativus, Pulvis Bubali Comus Concentratus, Moschus, Margarita, Cinnabaris, Realgar, Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, and Bomeolum Syntheticum, have been used for the treatment of stroke, encephalitis and emergency meningitis across Asia, especially in China for hundreds of years. OBJECTIVE: The goal of this study was to investigate the anti-atherosclerosis and cardio-protective effects of ANP administration using a rodent model of atherosclerosis induced by a high fat and vitamin D3. METHODS: Specific Pathogen-Free (SPF) 78 male SD rats were randomly divided into a control group and 5 atherosclerotic model groups. The atherosclerotic groups were divided to receive either Simvastatin (SVTT, 0.005g/kg), Low-dose ANP (0.125g/kg), Medium-dose ANP (0.25g/kg), and High-dose ANP (0.5g/kg). Following adaptive feeding for one week, atherosclerosis was induced and the atherosclerosis model was established. Experimental drugs (either simvastatin or ANP) or normal saline were administered intragastrically once daily for 9 weeks starting from the 8th week. A carotid artery ultrasound was performed at the 17th week to determine whether atherosclerosis had been induced. After the atherosclerosis model was successfully established, platelet aggregation rates, serum biochemical indices, apoptosis-related Bcl-2, Bax proteins levels in the heart were assayed. Pathological and histological analysis was completed using artery tissue from different experimental different groups to assess the effects of ANP. RESULTS: ANP significantly decreased aortic membrane thickness, the maximum platelet aggregation rates, and the ratio of low density lipoprotein cholesterol (LDL) to high density lipoprotein cholesterol (HDL). In addition, ANP significantly reduced serum contents of total cholesterol, low density lipoprotein, malondialdehyde, troponin I, high-sensitivity C-reactive protein, and lactate dehydrogenase. ANP markedly improved abnormal pathological conditions of the aorta and heart, and helped to prevent myocardial apoptosis. CONCLUSIONS: We have demonstrated that ANP has robust ant-atherosclerosis and cardio-protective effects on a high-fat and vitamin D3 - induced rodent model of atherosclerosis due to its antiplatelet aggregation, lipid regulatory, antioxidant, anti-inflammatory and anti-apoptotic properties.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Doenças das Artérias Carótidas/prevenção & controle , Colecalciferol , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologia , Hipolipemiantes/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/ultraestrutura , Doenças da Aorta/sangue , Doenças da Aorta/induzido quimicamente , Doenças da Aorta/diagnóstico por imagem , Apoptose/efeitos dos fármacos , Aterosclerose/sangue , Aterosclerose/induzido quimicamente , Aterosclerose/diagnóstico por imagem , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/induzido quimicamente , Doenças das Artérias Carótidas/diagnóstico por imagem , Modelos Animais de Doenças , Enzimas/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Miocárdio/patologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Ratos Sprague-Dawley , Sinvastatina/farmacologia , Comprimidos , Fatores de Tempo
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