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1.
J Biol Chem ; 298(5): 101899, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35398354

RESUMO

The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration of the cerebellum that results in movement disorder. Recently, a new heritable form of SCA, spinocerebellar ataxia type 48 (SCA48), was attributed to dominant mutations in STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these mutations cause SCA48. STUB1 encodes for the protein C terminus of Hsc70 interacting protein (CHIP), an E3 ubiquitin ligase. CHIP is known to regulate proteostasis by recruiting chaperones via a N-terminal tetratricopeptide repeat domain and recruiting E2 ubiquitin-conjugating enzymes via a C-terminal U-box domain. These interactions allow CHIP to mediate the ubiquitination of chaperone-bound, misfolded proteins to promote their degradation via the proteasome. Here we have identified a novel, de novo mutation in STUB1 in a patient with SCA48 encoding for an A52G point mutation in the tetratricopeptide repeat domain of CHIP. Utilizing an array of biophysical, biochemical, and cellular assays, we demonstrate that the CHIPA52G point mutant retains E3-ligase activity but has decreased affinity for chaperones. We further show that this mutant decreases cellular fitness in response to certain cellular stressors and induces neurodegeneration in a transgenic Caenorhabditis elegans model of SCA48. Together, our data identify the A52G mutant as a cause of SCA48 and provide molecular insight into how mutations in STUB1 cause SCA48.


Assuntos
Ataxias Espinocerebelares , Ubiquitina-Proteína Ligases , Ubiquitina , Humanos , Mutação , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
2.
Mol Psychiatry ; 27(3): 1742-1753, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34759357

RESUMO

Substance use disorders (SUDs) are moderately to highly heritable and are in part cross-transmitted genetically, as observed in twin and family studies. We performed exome-focused genotyping to examine the cross-transmission of four SUDs: alcohol use disorder (AUD, n = 4487); nicotine use disorder (NUD, n = 4394); cannabis use disorder (CUD, n = 954); and nonmedical prescription opioid use disorder (NMPOUD, n = 346) within a large nationally representative sample (n = 36,309), the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). All diagnoses were based on in-person structured psychiatric interview (AUDADIS-5). SUD cases were compared alone and together to 3959 "super controls" who had neither a SUD nor a psychiatric disorder using an exome-focused array assaying 363,496 SNPs, yielding a representative view of within-disorder and cross-disorder genetic influences on SUDs. The 29 top susceptibility genes for one or more SUDs overlapped highly with genes previously implicated by GWAS of SUD. Polygenic scores (PGS) were computed within the European ancestry (EA) component of the sample (n = 12,505) using summary statistics from each of four clinically distinct SUDs compared to the 3959 "super controls" but then used for two distinctly different purposes: to predict SUD severity (mild, moderate, or severe) and to predict each of the other 3 SUDs. Our findings based on PGS highlight shared and unshared genetic contributions to the pathogenesis of SUDs, confirming the strong cross-inheritance of AUD and NUD as well as the distinctiveness of inheritance of opioid use disorder.


Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Transtornos Relacionados ao Uso de Opioides , Transtornos Relacionados ao Uso de Substâncias , Tabagismo , Consumo de Bebidas Alcoólicas , Alcoolismo/psicologia , Comorbidade , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/genética , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tabagismo/psicologia
3.
Opt Lett ; 45(16): 4369-4372, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32796960

RESUMO

A tunable light absorption of graphene using topological interface states (TISs) is presented. The monolayer graphene is embedded in the interface of asymmetric topological photonic crystals (ATPCs). A strong absorption phenomenon occurs by the excitation of TISs. It is found that the absorption spectra are intensively dependent on the chemical potential of graphene and the periodic number of the ATPCs. Furthermore, the absorption can be rapidly switched in a slight variation of chemical potential, which is modulated by the applied gate voltage on graphene. This study not only opens up a new approach for enhancing light-monolayer graphene interactions, but also provides for practical applications in high absorption optoelectronic devices. This strong absorption phenomenon is different from those in Fabry-Perot resonators, nano-cavities photonic crystal, and traditional topological photonic crystals (TPCs).

4.
Eur J Neurol ; 27(8): 1647-1655, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32352616

RESUMO

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.


Assuntos
Isquemia Encefálica , Hiperglicemia , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Biomarcadores , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Humanos , Hiperglicemia/complicações , Hiperglicemia/genética , RNA Longo não Codificante , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Receptor fas
5.
Neurocrit Care ; 32(1): 311-316, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264070

RESUMO

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.


Assuntos
Pesquisa Biomédica , Cuidados Críticos , Neurologia , Neurocirurgia , Humanos , Sociedades Médicas
6.
Zhonghua Yi Xue Za Zhi ; 100(44): 3525-3528, 2020 Dec 01.
Artigo em Zh | MEDLINE | ID: mdl-33256296

RESUMO

Objective: To investigate the clinical application of multimodality navigation for liver resection in the treatment of complicated alveolar echinococcosis (AE). Methods: From October 2019 to February 2020, the clinical data and perioperative results of patients with AE treated by surgery in our department were retrospectively studied. Hepatic parenchyma disconnection plane and liver resection were navigated and performed with three-dimensional reconstruction and HITACHI real-time multi-image fusion interventional navigation system (RVS). Results: All of six patients were successful performed radical liver resection without mortality. The operation time was (301±106)min and the median blood loss was 200 ml. Two patients needed blood transfusion intraoperative (33.33%). The postoperative hospital stay was (10.8±2.8) day, and the cost of hospitalization was (82 584±995.61) yuan. Clavien-Dindo grade Ⅲ complication occurred in one patient. Conclusions: Multimodality navigation might provide precise intraoperative navigation of the surgical plane and effectively assist liver resection for the treatment of complicated AE.


Assuntos
Equinococose Hepática , Equinococose , Equinococose Hepática/cirurgia , Hepatectomia , Humanos , Fígado , Estudos Retrospectivos
7.
Zhonghua Wai Ke Za Zhi ; 58(3): 230-234, 2020 Mar 01.
Artigo em Zh | MEDLINE | ID: mdl-32187928

RESUMO

Objective: To compare the long term and short term outcomes between robotic and open surgery for hilar cholangiocarcinoma radical resection. Methods: This is a single-center and retrospective case-control study. Patients underwent hilar cholangiocarcinoma radical resection between January 2016 and December 2016 at Department of Hepatobiliary Surgery of the General Hospital of the Chinese People's Liberation Army were included. Safety, effectiveness and long-term prognosis of tumors were evaluated. Patients were divided into robotic hilar cholangiocarcinoma radical surgery group (robotic group, n=16) and open hepatic hilar cholangiocarcinoma radical surgery group (open group, n=31) . All cases were confirmed by pathology histological. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS) , and overall survival (OS) were retrospectively collected and analyzed.In the follow-up cohort, the primary outcome was patient death and the secondary outcome was tumor recurrence. Continuous variables were expressed as means and medians and were compared using the Student t test if normally distributed or Wilcoxon-Mann-Whitney test for nonparametric variables. Discrete variables were expressed as frequency and percentages and χ(2) or Fisher exact test, when appropriate, were used for comparisons. Kaplan-Meier curves were used to calculate the probability of survival and comparisons were performed using log-rank test. Results: In this study, compared with the open group, the robotic group had a longer operation time ( (338±71) minutes vs. (256±56) minutes, t=4.251, P=0.001) , but the intraoperative blood loss was less (100 ml vs. 200 ml, Z=121.50, P=0.040) , the gastric tube removal time was earlier (3 days vs. 4 days, Z=136.0, P=0.011) , and the postoperative hospital stay was shorter (9 days vs. 12 days, Z=144.50, P=0.040) , and the difference was statistically significant.There was no significant difference in the blood transfusion rate, R0 resection rate, and tumor size between the two groups.The recurrence rates in the robotic group and open surgery were 53.3% and 67.0%, respectively (χ(2)=1.04, P=0.307) .The median survival time of the robotic group and the open group was 22.0 months and 25.0 months. There was no significant difference in the overall survival rate between the two groups (P>0.05) . Conclusion: Compared with laparotomy, robotic HCC radical resection could have an equivalence or non-inferiority approach with acceptable long-term outcome.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Laparotomia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
8.
Mol Psychiatry ; 23(4): 1051-1065, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28439102

RESUMO

Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development. Focusing on the most dysregulated miRNAs, we found miR-199 and miR-214 to be increased during early brain development and to differentially regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase and protein kinase B (PKB/AKT) signaling. In parallel, we characterized the effects on human neurogenesis and neuronal differentiation brought about by MeCP2 deficiency using both monolayer and three-dimensional (cerebral organoid) patient-derived and MeCP2-deficient neuronal culture models. Inhibiting miR-199 or miR-214 expression in iPSC-derived neural progenitors deficient in MeCP2 restored AKT and ERK activation, respectively, and ameliorated the observed alterations in neuronal differentiation. Moreover, overexpression of miR-199 or miR-214 in the wild-type mouse embryonic brains was sufficient to disturb neurogenesis and neuronal migration in a similar manner to Mecp2 knockdown. Taken together, our data support a novel miRNA-mediated pathway downstream of MeCP2 that influences neurogenesis via interactions with central molecular hubs linked to autism spectrum disorders.


Assuntos
Sistema de Sinalização das MAP Quinases , Proteína 2 de Ligação a Metil-CpG/metabolismo , MicroRNAs/metabolismo , Neurogênese/fisiologia , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Diferenciação Celular/genética , Linhagem Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Camundongos , MicroRNAs/genética , Neurogênese/genética , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Síndrome de Rett/patologia , Transdução de Sinais
9.
Prev Med ; 118: 336-343, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508551

RESUMO

Moderate alcohol consumption has been related to lower risk of coronary heart disease (CHD) in the literature. To examine whether alcohol drinking during the past 12 months and heaviest drinking period were differentially associated with the risk of CHD, we designed a case-control study using a population-based health survey of U.S. adults conducted from 2012 to 2013. Respondents who reported to have doctor-ascertained CHD served as cases (n = 1671), and those free of CHD and other alcohol-related health conditions served as controls (n = 17,629) in logistic regressions. Sex-specific quartiles of average daily ethanol intake were ascertained and calculated for the past 12 months and during the period of heaviest lifetime drinking. We further split current drinkers into reducers and non-reducers (past 12 months relative to the heaviest drinking period) to examine CHD risk profiles in association with the 12-month drinking level. Current-drinker reducers (AOR, 95% CI = 1.57 [1.10-2.27] for men; AOR, 95% CI = 1.33 [1.02-1.72] for women) and former drinkers (AOR, 95% CI = 2.06 [1.43-2.97] for men; AOR, 95% CI = 1.51 [1.19-1.92] for women) more often had CHD than lifetime abstainers. Male heavy drinkers during the heaviest drinking period (AOR, 95% CI = 2.25 [1.52-3.32]) were more likely to manifest CHD than lifetime abstainers. In addition, individuals with diagnosed CHD were significantly more likely to have reduced drinking in the past. A change in alcohol consumption over the life course among former and current drinkers may distort the true alcohol-CHD relationship.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Doença das Coronárias/epidemiologia , Comportamentos Relacionados com a Saúde , Adulto , Estudos de Casos e Controles , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos
10.
Clin Exp Dermatol ; 44(6): 643-646, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30618056

RESUMO

Vitiligo-like depigmentation (VLD) is a characteristic cutaneous event described in patients with metastatic malignant melanoma receiving treatment with immune checkpoint inhibitors. We report the onset of VLD in three patients with other cancer types (cholangiocarcinoma, renal cell carcinoma and squamous cell carcinoma) following treatment with immunotherapy (combination pembrolizumab and nivolumab for the first, and pembrolizumab for the other two cancer types). Cases of VLD have not been reported previously in patients treated for any of these cancers, to our knowledge. Pembrolizumab and nivolumab are monoclonal antibodies targeting programmed cell death (PD)-1 receptors, while ipilimumab targets cytotoxic T-lymphocyte antigen-4. Our clinical finding challenges the current understanding of VLD as a malignant melanoma-specific immunotherapy-related adverse event.


Assuntos
Imunoterapia/efeitos adversos , Melanoma/secundário , Vitiligo/induzido quimicamente , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Humanos , Hipopigmentação/induzido quimicamente , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Transtornos da Pigmentação/induzido quimicamente , Transtornos da Pigmentação/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Vitiligo/patologia
11.
Phys Rev Lett ; 117(14): 144801, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27740829

RESUMO

Few-fs electron bunches from laser wakefield acceleration (LWFA) can efficiently drive plasma wakefields (PWFs), as shown by their propagation through underdense plasma in two experiments. A strong and density-insensitive deceleration of the bunches has been observed in 2 mm of 10^{18} cm^{-3} density plasma with 5.1 GV/m average gradient, which is attributed to a self-driven PWF. This observation implies that the physics of PWFs, usually relying on large-scale rf accelerators as drivers, can be studied by tabletop LWFA electron sources.

13.
Soc Psychiatry Psychiatr Epidemiol ; 51(8): 1137-48, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27106853

RESUMO

OBJECTIVES: To present current, nationally representative US findings on the past-year and lifetime prevalences, sociodemographic correlates, psychiatric comorbidity, associated disability, and treatment of DSM-5 posttraumatic stress disorder (PTSD). METHODS: Face-to-face interviews with 36,309 adults in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III. PTSD, alcohol and drug use disorders, and selected mood, anxiety, and personality disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. RESULTS: Past-year and lifetime prevalences were 4.7 and 6.1 %, higher for female, white, Native American, younger, and previously married respondents, those with

Assuntos
Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos de Ansiedade/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Transtornos da Personalidade/epidemiologia , Prevalência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Tempo para o Tratamento/estatística & dados numéricos , Estados Unidos/epidemiologia
14.
Phys Rev Lett ; 115(15): 155002, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26550730

RESUMO

An important limit for energy gain in laser-plasma wakefield accelerators is the dephasing length, after which the electron beam reaches the decelerating region of the wakefield and starts to decelerate. Here, we propose to manipulate the phase of the electron beam in the wakefield, in order to bring the beam back into the accelerating region, hence increasing the final beam energy. This rephasing is operated by placing an upward density step in the beam path. In a first experiment, we demonstrate the principle of this technique using a large energy spread electron beam. Then, we show that it can be used to increase the energy of monoenergetic electron beams by more than 50%.

15.
J Anim Physiol Anim Nutr (Berl) ; 98(4): 739-46, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24164218

RESUMO

Succinate dehydrogenase (SDH), Ca(2+) ATPase, Lactate dehydrogenase (LDH), are involved in energy metabolism. These enzymes can be used as indicators of the energy capacity of aerobic cells. The study investigated the effects of L-carnitine supplementation on M. pectoralis superficialis, M. pectoralis profundus, M. extensor carpi radialis muscle and M. flexor carpi ulnaris. Twenty-eight racing pigeons hatched at the same time were divided randomly into three groups. Eight pigeons, which were used as the control group, were sacrificed at 92-day old. The remaining twenty pigeons continued training until they reached 157-day old, with half the pigeons getting 25 mg/head/day of L-carnitine, while the other half given the same amount of water. The pigeons were assessed by histochemical methods and reverse transcription polymerase chain reaction (RT-PCR). To assess influence of L-carnitine on muscle fibre composition and the performance of three genes' mRNA, this study applied SDH localization, SDH, Ca(2+) ATPase and LDH mRNA expression to examine the results after oral administration of L-carnitine in vivo in racing pigeons. The results showed that L-carnitine significantly elevated the amount of white muscle fibre type IIa (p < 0.05). The mRNA expression quantities of SDH and LDH gene was higher via RT-PCR method. However, the expression of Ca(2+) ATPase remains similar. In conclusion, appropriate oral administration of L-carnitine of 25 mg/pigeon/day will result in an improvement of muscles related to flying.


Assuntos
Carnitina/farmacologia , Columbidae/fisiologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Drug Alcohol Depend ; 257: 111120, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38402754

RESUMO

BACKGROUND: National survey data suggest Asian Americans (AA) are less likely to consume alcohol and develop AUD than Americans in other groups. However, it is common for AA to be born outside of the US and carry gene variants that alter alcohol metabolism, both of which can lead to lower levels of alcohol involvement. The current study examined differences in alcohol use and AUD between AA and other groups before and after controlling for birth location and gene variants. DESIGN: Past year alcohol measures were examined from adults 18+ (N=22,848) in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III before and after controlling for birth location (inside or outside of the US) and gene variants (ALDH2*2 and ADH1B*2/ADH1B*3). Gender gaps in alcohol measures also were assessed. RESULTS: Before adjustments, AA were less likely than White Americans to drink in the previous year (OR=0.50, 95% CI 0.41-0.62), binge (OR=0.68, 95% CI 0.52-0.88), engage in frequent heavy drinking (OR=0.55, 95% CI 0.42-0.73), and reach criteria for AUD (OR=0.71, 95% CI 0.53-0.94). After controlling for birth location and gene variants, AA remained less likely to drink in the past year (OR=0.54, 95% CI 0.41-0.70) but all other differences disappeared. Gender gaps were only observed for AA born outside of the US, highlighting the importance of experience rather than racial category per se. CONCLUSIONS: Findings indicate that heterogeneity among AA leads to spurious generalizations regarding alcohol use and AUD and challenge the model minority myth.


Assuntos
Alcoolismo , Adulto , Humanos , Álcool Desidrogenase , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/epidemiologia , Alcoolismo/genética , Aldeído-Desidrogenase Mitocondrial , Asiático , Etanol , Brancos
17.
Cerebrovasc Dis ; 36(3): 181-188, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24135527

RESUMO

BACKGROUND: Recent genetic studies of stroke and related risk factors have identified a growing number of susceptibility loci; however, the relationship of these alleles to ischemic stroke is unknown. The challenge in finding reproducible loci of ischemic stroke susceptibility may be in part related to the etiologic heterogeneity in clinically defined stroke subtypes. In this study, we tested whether known single nucleotide polymorphisms (SNPs) associated with stroke or putative stroke risk factors are associated with neuropathologically defined micro- or macroscopic infarcts and with arteriolosclerosis. METHODS: Measures of neuropathology and genotyping were available from 755 deceased participants from the Religious Orders Study and the Rush Memory and Aging Project. All donated brains were examined by a board-certified neuropathologist using standardized protocol for the presence of microscopic infarct, macroscopic infarct and arteriolosclerosis (lipohyalinosis). In primary analysis, 74 candidate SNPs previously associated (p < 5 × 10(-8)) with ischemic stroke or known risk factors, including atrial fibrillation (AF), hypertension, diabetes, low-density lipoprotein (LDL) level and carotid artery stenosis, were evaluated for association with neuropathologic endpoints. We performed a secondary exploratory analysis to include 93 additional SNPs associated with putative ischemic stroke risk factors including SNPs associated with high-density lipoprotein (HDL), triglyceride serum levels, myocardial infarction (MI), coronary artery disease and cerebral white matter disease. Regression models relating SNPs to cerebrovascular neuropathology were adjusted for age at death, gender and cohort membership. RESULTS: The strongest associations seen for both macroscopic and microscopic infarcts were risk variants associated with diabetes. The diabetes risk variant rs7578326 located near the IRS1 locus was associated with both macroscopic (OR = 0.73, p = 0.011) and microscopic (OR = 0.71, p = 0.009) infarct pathology. Another diabetes susceptibility locus (rs12779790) located between the calcium/calmodulin-dependent protein kinase ID (CAMK1D) and cell division cycle 123 homolog (CDC123) genes is also associated with both macroscopic (OR = 1.40, p = 0.0292) and microscopic infarcts (OR = 1.43, p = 0.0285). The diabetes risk variant rs864745 within JAZF1 was associated with arteriolosclerosis (OR = 0.80, p = 0.014). We observed suggestive associations with the diabetes risk variant rs7961581 (p = 0.038; between TSPAN8 and LGR5) and rs5215 (p = 0.043; KCNJ11), the LDL risk variant rs11206510 (p = 0.045; PCSK9), as well as the AF risk locus ZFHX3. The CDKN2A/B locus (rs2383207, 9p21), identified initially as a susceptibility allele for MI and recently implicated in large vessel stroke, was associated with macroscopic infarct pathology in our autopsy cohort (OR = 1.26, p = 0.031). CONCLUSION: Our results suggest replication of the candidate CDKN2A/B stroke susceptibility locus with directly measured macroscopic stroke neuropathology, and further implicate several diabetes and other risk variants with secondary, pleiotropic associations to stroke-related pathology in our autopsy cohort. When coupled with larger sample sizes, cerebrovascular neuropathologic phenotypes will likely be powerful tools for the genetic dissection of susceptibility for ischemic stroke.


Assuntos
Arteriolosclerose/genética , Predisposição Genética para Doença , Infarto/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/genética
18.
Compr Psychiatry ; 54(6): 627-38, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23522830

RESUMO

Clinical and epidemiologic evidence has documented the significant associations between medical illnesses and psychiatric disorders. However, extensive research has focused on the comorbidity of medical conditions and depression, and most were cross sectional, focused on clinical samples, and grounded in DSM-III or DSM-III-R diagnostic criteria. The current prospective investigation examined associations among medical conditions at baseline and incident psychiatric disorders over a 3-year follow-up, using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Overall, the 3-year incidence rates of DSM-IV substance use, mood and anxiety disorders ranged from 0.65% (bipolar II) to 5.2% (alcohol abuse). Multiple regression analysis was conducted to examine the prospective physical-mental associations, while controlling for sociodemographic characteristics, psychological stress and health-related risk factors, and comorbid physical and psychiatric disorders. The present study represents, to our knowledge the largest population-based prospective study examining the physical-mental associations. Our results showed distinctly different patterns of comorbidity of medical illnesses with substance use, mood, and anxiety disorders. Stomach ulcer/gastritis, hypertension and arthritis emerged to be significant predictors of incident psychiatric disorders.


Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos de Ansiedade/epidemiologia , Doenças Cardiovasculares/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos do Humor/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Fatores de Risco
19.
Anaesthesia ; 68(8): 851-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24044439

RESUMO

We compared direct laryngoscopy with a Macintosh blade vs indirect bronchoscopy with a Trachway® stylet, for endobronchial intubation with a left-sided double-lumen tube. We allocated participants scheduled for thoracic surgery and who had normal predicted laryngoscopy, 30 to each group. The mean (SD) intubation times with laryngoscope and Trachway were 48 (11) s vs 28 (4) s, respectively, p < 0.001. The rates of hoarseness on the first postoperative day, categorised as none/mild/moderate/severe, were 10/12/7/1 and 22/6/2/0, respectively, p = 0.008, without differences on subsequent days. Left endobronchial intubation with a double-lumen tube is slower using direct laryngoscopy and causes more hoarseness than indirect bronchoscopy with a Trachway stylet.


Assuntos
Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/métodos , Adulto , Anestesia por Inalação , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Rouquidão/epidemiologia , Rouquidão/etiologia , Humanos , Masculino , Éteres Metílicos , Pessoa de Meia-Idade , Monitorização Intraoperatória , Faringite/epidemiologia , Faringite/etiologia , Complicações Pós-Operatórias/epidemiologia , Sevoflurano , Gravação em Vídeo
20.
Int J Sports Med ; 34(9): 841-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23444084

RESUMO

This study compares the serological markers between runners who are hepatitis B virus carries (HBVc) and runners who are non-HBVc in a 100-km ultra-marathon race. Blood samples of 8 HBVc and 18 non-HBVc runners were drawn 1 week before, immediately following, and 24 h after the race. Samples were analyzed and compared between the 2 groups for liver function tests, muscle damage markers and oxidative stress cytokines. For HBVc runners, HBV-DNA (hepatitis B virus-deoxyribonucleic acid) levels were also evaluated for virus reactivation. The results demonstrate a statistically significant increase in both immediate and 24-h post-race values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), compared with pre-race values. No statistically significant difference was observed between the 2 groups for the values of AST, LDH, CK, hs-CRP, IL-6 and TNF-α either before or after the race. There was also no statistically significant change in the levels of HBV-DNA in HBVc runners. These findings suggest that HBVc runners do not have higher risks of liver function impairment, muscle breakdown and inflammatory response compared to non-HBVc runners in such endurance races.


Assuntos
Portador Sadio , Hepatite B/virologia , Fígado/metabolismo , Corrida/fisiologia , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , DNA Viral/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Fígado/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Resistência Física/fisiologia , Adulto Jovem
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