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1.
Blood ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276273

RESUMO

E2A, a basic helix-loop-helix (bHLH) transcription factor, plays a crucial role in determining tissue-specific cell fate, including differentiation of B cell lineages. In 5% of childhood acute lymphoblastic leukemia (ALL), the t(1,19) chromosomal translocation specifically targets the E2A gene and produces an oncogenic E2A-PBX1 fusion protein. While previous studies have demonstrated oncogenic functions of E2A-PBX1 in cell and animal models, the E2A-PBX1-enforced cistrome, the E2A-PBX1 interactome, and related mechanisms underlying leukemogenesis remain unclear. Here, by unbiased genomic profiling approaches, we identify the direct target sites of E2A-PBX1 in t(1,19)-positive pre-B ALL cells and show that, compared to normal E2A, E2A-PBX1 preferentially binds to a subset of gene loci co-bound by RUNX1 and gene-activating machineries (p300, MED1, and H3K27 acetylation). Using biochemical analyses, we further document a direct interaction of E2A-PBX1, through a region spanning the PBX1 homeodomain, with RUNX1. Our results also show that E2A-PBX1 binding to gene enhancers is dependent on the RUNX1 interaction, but not the DNA-binding activity harbored within the PBX1 homeodomain of E2A-PBX1. Transcriptome analyses and cell transformation assays further establish a significant RUNX1 requirement for E2A-PBX1-mediated target gene activation and leukemogenesis. Notably, the RUNX1 locus itself is also directly activated by E2A-PBX1, indicating a multilayered interplay between E2A-PBX1 and RUNX1. Collectively, our study provides the first unbiased profiling of the E2A-PBX1 cistrome in pre-B ALL cells and reveals a previously unappreciated pathway in which E2A-PBX1 acts in concert with RUNX1 to enforce transcriptome alterations for the development of pre-B ALL.

2.
BMC Infect Dis ; 19(1): 536, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215414

RESUMO

BACKGROUND: Enterobius vermicularis (pinworm) is one of the most common human parasitic helminths, and children are the most susceptible group. Some behavioral and environmental factors may facilitate pinworm infection. In the Republic of the Marshall Islands (RMI), the status of pinworm infections among children remains unknown. METHODS: In Majuro City, there are 14 kindergartens with a total of 635 preschool children (PSC) whose age range of 5~6 years. The present investigation attempted to determine the pinworm prevalence and associated risk factors as well as investigate whether eggs contaminated the clothes of PSC or the ground and tables in classrooms of 14 kindergartens. Informed consent form and a self-administered questionnaire were given to parents prior to pinworm screening. Perianal specimens were collected by an adhesive scotch tape method, and clothing of belly and hip sites and the ground and tables of the classrooms were inspected using a cellophane tape method to detect any eggs contamination. RESULTS: In total, 392 PSC (5.28 ± 0.56 yrs. old) participated in this project. The overall prevalence of pinworm infection was 22.4% (88/392). Boys (24.5%) had higher prevalence than girls (20.31%) (p = 0.32). PSC aged > 5 years (32.77%) showed a significantly higher prevalence than those aged ≤5 years (17.95%) (p = 0.01). A univariate analysis indicated that PSC who lived in urban areas (22.95%) had a higher prevalence than those who lived in rural areas (20.69%) (p = 0.69). The employment status of the parents showed no association with the pinworm infection rate (p > 0.05). A logistic regression analysis indicated that "having an older sister" produced a higher risk of acquiring pinworm infection for PSC compared to those who did not have an older sister (OR = 2.02; 95%CI = 1.05~3.88; p = 0.04). No significant association between various other risk factors and pinworm infection was found (p > 0.05). Also, no eggs contamination was found on the clothes of the belly and hip sites or on the ground and tables in the 14 kindergartens. CONCLUSIONS: Mass screening and treatment of infected PSC are important measures in pinworm control in the RMI.


Assuntos
Enterobíase/diagnóstico , Animais , Criança , Pré-Escolar , Enterobíase/epidemiologia , Enterobius/isolamento & purificação , Feminino , Humanos , Modelos Logísticos , Masculino , Micronésia/epidemiologia , Pais , Prevalência , Fatores de Risco , População Rural , Inquéritos e Questionários
3.
Artigo em Inglês | MEDLINE | ID: mdl-30499423

RESUMO

AIM: The study was conducted in order to examine the sex-specific association of serum uric acid (SUA) levels with elevated serum alanine aminotransferase (ALT) in a Taiwanese military cohort. METHODS: We made a cross-sectional examination of the sex-specific relationship using 6728 men and 766 women, aged 18-50 years from a large military cohort in Taiwan. SUA levels within the reference range (<7.0 mg/dL for men and <5.7 mg/dL for women respectively) were divided into quartiles and SUA levels greater than the upper reference limits were defined as hyperuricemia. Elevated ALT levels were defined as ≥40 U/L. Multivariate logistic regression analysis was performed to determine the association between each SUA category and elevated ALT levels in men and women, respectively. RESULTS: The prevalence of hyperuricemia and elevated ALT in men were 18.7% and 12.7%, respectively, and in women were 3.3% and 2.1%, respectively. As compared with the lowest SUA quartile, hyperuricemia was associated with elevated ALT in men (odds ratios (OR): 1.62, 95% confidence intervals (CI): 1.19-2.20) after controlling for age, service specialty, body mass index, metabolic syndrome components, current cigarette smoking, alcohol intake status, and weekly exercise times, but the associations for the other SUA quartiles were null. By contrast, the associations of hyperuricemia (OR: 0.81, 95% CI: 0.10-6.64) and the other SUA quartiles with elevated ALT were null in women. CONCLUSION: Our findings suggest that the relationship between each SUA level and elevated ALT may differ by sex among military young adults. The mechanism for the sex difference requires further investigations.


Assuntos
Alanina Transaminase/sangue , Aptidão Cardiorrespiratória/fisiologia , Militares , Caracteres Sexuais , Ácido Úrico/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Environ Toxicol ; 33(12): 1321-1328, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30259639

RESUMO

4-methylimidazole (4-MI) is an imidazole-derived organic chemical compound that can be used as a raw material in the manufacture of diverse chemicals and has been identified as an ingredient of caramel color in soybean sauce, beers, and other soft drinks. The aim of the present study was to investigate the teratogenic effects of 4-MI during zebrafish embryogenesis. Zebrafish embryos were treated with different dosages of 4-MI (0-120 mM) for different exposure durations (12-60 hours). The percentages of embryos with malformed phenotypes increased as the exposure dosages and duration time of 4-MI increased. We also used immunofluorescence and transmission microscopy to evaluate the subtle changes in the myofibril alignment and ultrastructure of muscle organization. Our data showed that 4-MI treatment disturbs muscle fiber alignment. Electron microscopy data indicated that Z-lines were undetectable in the 4-MI-treated embryos. Although the thick and thin filaments were visible, they were all disorganized. In addition, zebrafish embryos treated by 4-MI exhibited aberrant expression of 2 muscle-specific genes, myod and myogenin. Taken together, we concluded that early exposure to 4-MI affects zebrafish myogenesis, especially in myofibril alignment.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Imidazóis/toxicidade , Desenvolvimento Muscular/efeitos dos fármacos , Miofibrilas/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Miofibrilas/fisiologia , Proteínas de Peixe-Zebra/metabolismo
5.
Cell Commun Signal ; 16(1): 19, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703230

RESUMO

BACKGROUND: Golgin-97 is a tethering factor in the trans-Golgi network (TGN) and is crucial for vesicular trafficking and maintaining cell polarity. However, the significance of golgin-97 in human diseases such as cancer remains unclear. METHODS: We searched for a potential role of golgin-97 in cancers using Kaplan-Meier Plotter ( http://kmplot.com ) and Oncomine ( www.oncomine.org ) datasets. Specific functions of golgin-97 in migration and invasion were examined in golgin-97-knockdown and golgin-97-overexpressing cells. cDNA microarray, pathway analysis and qPCR were used to identify gene profiles regulated by golgin-97. The role of golgin-97 in NF-κB signaling pathway was examined by using subcellular fractionation, luciferase reporter assay, western blot analysis and immunofluorescence assay (IFA). RESULTS: We found that low expression of golgin-97 correlated with poor overall survival of cancer patients and was associated with invasiveness in breast cancer cells. Golgin-97 knockdown promoted cell migration and invasion, whereas re-expression of golgin-97 restored the above phenotypes in breast cancer cells. Microarray and pathway analyses revealed that golgin-97 knockdown induced the expression of several invasion-promoting genes that were transcriptionally regulated by NF-κB p65. Mechanistically, golgin-97 knockdown significantly reduced IκBα protein levels and activated NF-κB, whereas neither IκBα levels nor NF-κB activity was changed in TGN46- or GCC185-knockdown cells. Conversely, golgin-97 overexpression suppressed NF-κB activity and restored the levels of IκBα in golgin-97-knockdown cells. Interestingly, the results of Golgi-disturbing agent treatment revealed that the loss of Golgi integrity was not involved in the NF-κB activation induced by golgin-97 knockdown. Moreover, both TGN-bound and cytosolic golgin-97 inhibited NF-κB activation, indicating that golgin-97 functions as an NF-κB suppressor regardless of its subcellular localization. CONCLUSION: Our results collectively demonstrate a novel and suppressive role of golgin-97 in cancer invasiveness. We also provide a new avenue for exploring the relationship between the TGN, golgin-97 and NF-κB signaling in tumor progression.


Assuntos
Autoantígenos/metabolismo , Neoplasias da Mama/patologia , Proteínas da Matriz do Complexo de Golgi/metabolismo , NF-kappa B/metabolismo , Rede trans-Golgi/metabolismo , Autoantígenos/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Bases de Dados Factuais , Feminino , Proteínas da Matriz do Complexo de Golgi/antagonistas & inibidores , Proteínas da Matriz do Complexo de Golgi/genética , Humanos , Estimativa de Kaplan-Meier , Glicoproteínas de Membrana/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-29562671

RESUMO

The association of metabolic syndrome (MetS) components with elevated serum alanine aminotransferase (ALT) levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18-50 years, from the cardiorespiratory fitness study in armed forces (CHIEF) in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF) ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR) and 95% confidence intervals: 1.59 (1.34-1.90), 1.40 (1.19-1.65), 2.00 (1.68-2.39), and 1.68 (1.38-2.04); all p < 0.001); whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35-24.51), p = 0.001) and ALT ≥ 30 U/L (2.67 (0.89-7.95), p = 0.08). Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women.


Assuntos
Alanina Transaminase/sangue , Síndrome Metabólica/sangue , Militares , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Caracteres Sexuais , Taiwan/epidemiologia , Adulto Jovem
7.
Oncol Lett ; 15(1): 91-98, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29375706

RESUMO

Radiosurgery serves an important function in the treatment of patients with intraocular tumors and preserves visual function via organ conservation. Therefore, it is important to ensure the safety and precision of GK-SRS as a primary treatment for intraocular tumors. The present case study described a 57-year-old female with uveal melanoma treated with GK-SRS. Retrobulbar anesthesia following fixation of the treated eye, via the suture of two of the extraocular muscles to the stereotactic frame, was performed to immobilize the eye during treatment. Computed tomography (CT) scans were performed following eye fixation, immediately prior to and following GK-SRS, to validate the accuracy of the tumor localization. The eye movement analysis revealed that the gravity center point deviations of the tumor and lens during treatment were <0.110 mm. At least 95% of the tumor volume was covered by the prescription dose according to three sets of CT images. The patient underwent a trans pars plana vitrectomy owing to a right eye vitreous hemorrhage. A 37-month follow-up assessment revealed tumor shrinkage, and the disappearance of the serous retinal detachments was noted on the basis of ophthalmoscopy and orbital magnetic resonance imaging. No major complications developed during the follow-up period. Using our treatment protocol, GK-SRS is a non-invasive procedure which is used as a brief single fraction treatment for intraocular tumor. The eye fixation method used in the present study has high accuracy.

8.
J Appl Clin Med Phys ; 18(6): 114-122, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960724

RESUMO

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications.


Assuntos
Neoplasias Encefálicas/cirurgia , Neuroma Acústico/cirurgia , Planejamento de Assistência ao Paciente/normas , Radiocirurgia/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Algoritmos , Tronco Encefálico/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
9.
Acta Trop ; 176: 242-248, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28847672

RESUMO

Intestinal parasitic infections (IPIs) among schoolchildren in Republic of Marshall Islands (RMI) largely remains unknown, thus investigation on IPIs status to establish the baseline data is urgently needed. This cross-sectional study intended to investigate the current IPIs status and associated risk factors among schoolchildren at capital of RMI. Single stool sample from 400 schoolchildren (207 boys and 193 girls) aged 9.73±2.50 yrs old was examined by employing merthiolate-iodine-formaldehyde concentration method. Demographic characteristics, uncomfortable symptoms and risk factors were obtained by questionnaires investigation. The overall prevalence of IPIs in schoolchildren was 22.8% (91/400), of them 24.2% harbored at least 2 different parasites. Notably, the majority was infected by waterborne protozoan parasites (82.4%, 75/91). Nine different intestinal parasites have been identified, of which six were pathogenic including Hook worm, Trichuris trichiura, Enterobius vermicularis, Entamoeba histolytica/dispar, Giardia intestinalis and Blastocystis hominis. Schoolchildren who ever complained dizziness or headache showed a significant higher prevalence of pathogenic IPIs than those who did not (p<0.05). Schoolchildren who lived in urban area than rural area had higher chance to acquire pathogenic IPIs (p=0.03). However, none of risk factors were identified to be associated with pathogenic IPIs.


Assuntos
Enteropatias Parasitárias/epidemiologia , Animais , Blastocystis hominis/isolamento & purificação , Criança , Estudos Transversais , Entamoeba histolytica/isolamento & purificação , Enterobius/isolamento & purificação , Fezes/parasitologia , Feminino , Giardia lamblia/isolamento & purificação , Humanos , Enteropatias Parasitárias/parasitologia , Masculino , Micronésia/epidemiologia , Prevalência , Características de Residência , Fatores de Risco , Trichuris/isolamento & purificação
10.
World J Gastroenterol ; 23(25): 4587-4594, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28740347

RESUMO

AIM: To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. METHODS: We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B (n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected (n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. RESULTS: Chronic hepatitis B negatively correlated with 2-min push-up numbers (ß = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (ß = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (ß = -1.47, P = 0.040). CONCLUSION: Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/fisiopatologia , Militares/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Aptidão Física/fisiologia , Adulto , Alanina Transaminase/sangue , Índice de Massa Corporal , Estudos Transversais , Exercício Físico , Hepacivirus/isolamento & purificação , Vírus da Hepatite A Humana/isolamento & purificação , Antígenos de Superfície da Hepatite B/isolamento & purificação , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia , Ultrassonografia , Adulto Jovem
11.
Traffic Inj Prev ; 18(2): 193-198, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-27753508

RESUMO

OBJECTIVE: Bicycle riding is increasingly popular in Taiwan, but the number of cyclists injured and cyclists' death rates are both increasing. The aim of this study was to investigate the different characteristics and clinical outcomes of traffic accident-related head injuries among cyclists in urban and rural areas. METHODS: Records of 812 patients (533 urban and 279 rural) admitted to 27 hospitals in Taipei City and Hualien County as the result of a traumatic head injury while bicycling between 1998 and 2013 were retrieved for study. Demographics, details about the accident, protective helmet use, and clinical outcomes were then subjected to analysis. RESULTS: Urban victims were more likely to be injured during morning and early evening rush hours and rural victims during the day; most urban victims were between 19 and 34 years of age and injured in the slow lane; rural victims tended to be younger or older and were injured in the fast lane (all P ≤.001). Riders who wore a helmet were less likely to suffer loss of consciousness (odds ratio [OR] = 0.31), amnesia (OR = 0.069), neurological disorders (OR = 0.205), or facial fractures (OR = 0.369). Older age, more severe head injuries, and bicycle-motor vehicle collisions influenced the severity of symptoms on admission and the residual effects at discharge. CONCLUSIONS: Differences in the characteristics of injuries in urban and rural areas and the utilization of protective helmets may help government authorities adopt appropriate policies to promote safer and more enjoyable cycling.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Ciclismo/lesões , Traumatismos Craniocerebrais/epidemiologia , Dispositivos de Proteção da Cabeça/estatística & dados numéricos , Adulto , Idoso , Traumatismos Craniocerebrais/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Admissão do Paciente/estatística & dados numéricos , Fatores de Risco , População Rural , Índice de Gravidade de Doença , Taiwan/epidemiologia , População Urbana , Adulto Jovem
12.
Dev Med Child Neurol ; 59(1): 52-56, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27346658

RESUMO

AIM: The aim of the study was to investigate the risk of stroke in patients with cerebral palsy (CP), based on nationwide data in Taiwan. METHOD: This prospective cohort study was comprised of patients recorded on the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005) who had a diagnosis of CP (n=1975) in records between 1 January 2004 and 31 December 2007. A comparison group (1:5) drawn from the same database was matched for age and sex (n=9875). Each patient was tracked by data until the development of stroke or the end of 2008. Cox proportional-hazards regression analysis was used to evaluate the hazard ratios after adjusting for potential confounding factors. RESULTS: Patients with CP were more likely to suffer stroke than the comparison population, after adjusting for potential confounding factors (adjusted hazard ratio: 2.17; 95% confidence interval [CI]: 1.74-2.69). The hazard ratio of stroke was 4.78 (95% CI: 3.18-7.17) and 1.57 (95% CI: 1.20-2.05) for patients with CP aged 50 years and under, and over 50 years respectively. INTERPRETATION: Cerebral palsy is a risk factor or marker for stroke that is independent of traditional stroke risk factors. Further research in this area is warranted.


Assuntos
Paralisia Cerebral/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Estatísticas não Paramétricas , Taiwan/epidemiologia , Adulto Jovem
13.
Biomed Res Int ; 2016: 6408067, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27051667

RESUMO

AIM: To summarize the covered or uncovered SEMS for treatment of unresectable malignant distal biliary obstruction, comparing the stent patency, patient survival, and incidence of adverse events between the two SEMSs. METHODS: The meta-analysis search was performed independently by two of the authors, using MEDLINE, EMBASE, OVID, and Cochrane databases on all studies between 2010 and 2015. Pooled effect was calculated using either the fixed or the random effects model. RESULTS: Statistics shows that there is no difference between SEMSs in the hazard ratio for patient survival (HR 1.04; 95% CI, 0.92-1.17; P = 0.55) and stent patency (HR 0.87, 95% CI: 0.58 to 1.30, P = 0.5). However, incidence of adverse events (OR: 0.74, 95% CI: 0.57 to 0.97, P = 0.03) showed significant different results in the covered SEMS, with dysfunctions events (OR: 0.75, 95% CI: 0.56 to 1.00, P = 0.05) playing a more important role than complications (OR: 0.87, 95% CI: 0.58 to 1.30, P = 0.50). CONCLUSIONS: Covered SEMS group had lower incidence of adverse events. There is no significant difference in dysfunctions, but covered SEMS trends to be better, with no difference in stent patency, patient survival, and complications.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Colestase/cirurgia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/instrumentação , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Procedimentos Cirúrgicos do Sistema Biliar/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Stents/estatística & dados numéricos
14.
J Neurotrauma ; 33(22): 2044-2054, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-26972789

RESUMO

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-ß precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.


Assuntos
Concussão Encefálica/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Mediadores da Inflamação/antagonistas & inibidores , Desempenho Psicomotor/efeitos dos fármacos , Animais , Concussão Encefálica/metabolismo , Concussão Encefálica/psicologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Injeções Subcutâneas , Masculino , Desempenho Psicomotor/fisiologia , Ratos , Ratos Sprague-Dawley
15.
Psychophysiology ; 53(4): 455-64, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26560198

RESUMO

Depression is one of the frequent complications following a mild traumatic brain injury (mTBI). Recent research indicated that abnormalities in the autonomic nervous system (ANS) can be evaluated by a noninvasive power spectral analysis of the heart rate variability (HRV). In this study, we investigated whether a frequency-domain analysis of HRV was correlated with late depression in mTBI patients. In total, 181 patients diagnosed with mTBI and 83 volunteers as healthy controls were recruited in 2010-2014. Beck Depression Inventory (BDI) scores were used to evaluate depression in the 1st week of assessment and at 1.5-, 3-, 6-, 12-, and 18-month follow-ups. Correlation and logistic regression analyses of the 1st week HRV parameters with BDI scores at 18 months were performed in individual female mTBI patients. Female mTBI patients were more vulnerable to depression accompanied by reduced HRV compared to healthy controls. Over time, depression was aggravated in female mTBI patients but was alleviated in male mTBI patients. A significantly lower parasympathetic proportion of the ANS was noted at 18 months with respect to the 1st week in female mTBI patients. In addition, depression in female mTBI patients at 18 months after injury was significantly correlated with a decrease in the parasympathetic proportion of the ANS in the 1st week (ρ = -0.411; p < .05). Dysautonomia resulted in higher risks of depression in female mTBI patients. We concluded that early dysautonomia following an mTBI contributes to late depression in female mTBI patients.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Lesões Encefálicas Traumáticas/complicações , Transtorno Depressivo/etiologia , Frequência Cardíaca/fisiologia , Disautonomias Primárias/diagnóstico , Adulto , Lesões Encefálicas Traumáticas/fisiopatologia , Transtorno Depressivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disautonomias Primárias/complicações , Disautonomias Primárias/fisiopatologia , Fatores Sexuais , Adulto Jovem
16.
Clin Neurophysiol ; 127(2): 1629-1638, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26350409

RESUMO

OBJECTIVE: Patients who have experienced a mild traumatic brain injury (mTBI) are susceptible to symptoms of anxiety or depression. To explore the potential biomarkers for emotional disorders in mTBI patients, we analyzed the frequency domain of heart rate variability (HRV) and serum concentrations of four neurohormones. METHODS: We assessed mTBI patients on their first visit and follow-up. Symptoms were evaluated by the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. Serum levels of adrenocorticotropic hormone (ACTH), melatonin, cortisol, and insulin-like growth factor (IGF)-1 and HRV follow-ups were measured and compared. RESULTS: mTBI patients were more vulnerable to symptoms of anxiety or depression than healthy controls. Reduced HRV was noted in mTBI patients compared to healthy controls. The mTBI patients demonstrated higher serum levels of ACTH, lower IGF-1 compared to healthy controls. In correlation analysis, only IGF-1 was positively correlated with HRV in mTBI patients. Both HRV and IGF-1 were correlated with symptom of depression while only HRV was correlated with symptom of anxiety in mTBI patients. CONCLUSIONS: We infer that HRV may be more significantly correlated with emotional disorders than is IGF-1 in mTBI patients. SIGNIFICANCE: The study is relevant for specific diagnostic markers in mTBI patients.


Assuntos
Ansiedade/sangue , Lesões Encefálicas/sangue , Depressão/sangue , Frequência Cardíaca/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Sintomas Afetivos/sangue , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/psicologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Biomarcadores/sangue , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/psicologia , Estudos de Coortes , Depressão/diagnóstico , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Adulto Jovem
17.
Disabil Rehabil ; 38(17): 1652-63, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26678282

RESUMO

BACKGROUND: To analyse the disability status of elderly Taiwanese dementia patients by using the World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0). METHODS: We enrolled 12 126 disabled elderly (>65 years) patients with dementia during July 2012-January 2014 from the Taiwan Data Bank of Persons with Disability. Trained interviewers evaluated the standardised scores in the six WHODAS 2.0 domains. Student's t test was used for comparing WHODAS 2.0 scores of male and female dementia patients with different age groups. RESULTS: The study population comprised 12 126 patients; 7612 were women and 4514 were men. The WHODAS 2.0 scores showed that the dementia patients had global activity limitation and participation restriction in all domains. Dementia-induced disability was prominent in male patients in all of the domains of the WHODAS 2.0. The domains of life activities, getting along with people and cognition were more strongly affected than the other domains. However, women experienced more rapid functional decline than men did as they aged. CONCLUSION: The data analysed in this large-scale, population-based study revealed crucial information on dementia-induced disability in elderly patients on the basis of the WHODAS 2.0 framework. Implications for rehabilitation Dementia patients have global functional disability in all domains of WHODAS 2.0 and multidisciplinary team is needed for rehabilitation programme intervention for these patients. When considering the rehabilitation resource and strategy, the domains of cognition, activities of daily living and life activities should be focussed. When dementia patients aged 65-75 years old, male patients got more restriction of function than female and more medical resource allocation for disabled male patients is recommended. With ageing, female dementia patients exhibited more rapid functional decline than male patients did and more budget about rehabilitation for maintain functional and dementia progression is crucial for female patients.


Assuntos
Demência/epidemiologia , Demência/psicologia , Avaliação da Deficiência , Pessoas com Deficiência , Atividades Cotidianas , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Cognição , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Análise de Regressão , Índice de Gravidade de Doença , Distribuição por Sexo , Taiwan/epidemiologia , Organização Mundial da Saúde
18.
Arch Toxicol ; 90(1): 191-202, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25238743

RESUMO

Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. Exposure of neuro-2a cells to oxygen/glucose deprivation (OGD) or cobalt chloride decreased cell viability and induced cell apoptosis in time-dependent manners. In parallel, OGD caused augmentation of cellular Bax and cytochrome c levels, a reduction in the mitochondrial membrane potential (MMP), activation of caspase-3, and fragmentation of DNA. miR-1 was induced in neuro-2a cells by OGD. Knocking down miR-1 expression using specific antisense inhibitors significantly alleviated OGD-induced neuronal death. Administration of OGD to neuro-2a cells induced heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search revealed that miR-1-specific binding elements exist in the 3'-untranslated region of HSP-70 mRNA. Overexpression of miR-1 simultaneously attenuated OGD-induced HSP-70 mRNA and protein expressions. In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax-mitochondrion-caspase protease pathway.


Assuntos
Apoptose , MicroRNAs/metabolismo , Neurônios/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Cobalto/toxicidade , Fragmentação do DNA , Regulação da Expressão Gênica , Glucose/deficiência , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oxigênio/metabolismo , Transdução de Sinais , Fatores de Tempo , Transfecção
19.
Eur J Clin Invest ; 45(12): 1297-305, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26479875

RESUMO

BACKGROUND: Exercise preconditioning (EP(+) ) has been widely accepted as a being of safe and effective preventive measure for stroke. The purpose of this study was to investigate whether EP(+) improves outcomes of ischaemic stroke by promoting neuronal and glial expression of heat shock protein (HSP) 20. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (288 in number) were used to investigate the contribution of HSP20-containing neurons and HSP20-containing glial cells in the exercise-mediated neuroprotection in the stroke condition using middle cerebral artery occlusion. RESULTS: Exercise preconditioning, in addition to increasing the numbers of both the HSP20-containg neurons (88 ± 8 vs. 43 ± 4; n = 8 each group; P < 0·05) and the HSP20-containg astrocytes (102 ± 10 vs. 56 ± 5; n = 8; P < 0·05) significantly attenuated stroke-induced brain infarct (140 ± 9 vs. 341 ± 20 mm(3) ; n = 8 per group; P < 0·01), neuronal apoptosis (20 ± 5 vs. 87 ± 7; n = 8 per group; n = 8; P < 0·01), glial apoptosis (29 ± 5 vs. 101 ± 4; n = 8; P < 0·01), and neurological deficits (6·6 ± 0·3 vs. 11·7 ± 0·8; n = 8 per group; P < 0·01). Reducing the numbers of both HSP20-containing neurons and HSP20-contaiing glia by intracerebral injection of pSUPER small interfering RNAί expressing HSP20 significantly reversed the beneficial effects of EP(+) in attenuating stroke-induced cerebral infarct, neuronal and glial apoptosis, and neurological deficits. CONCLUSIONS: The numbers of both the HSP20-containing neurons and the HSP20-containing glia inversely correlated with the outcomes of ischaemic stroke. In addition, preischaemic treadmill exercise improves outcomes of ischaemic stroke by increasing the numbers of both the HSP20-containing neurons and the HSP20-containing glia.


Assuntos
Proteínas de Choque Térmico HSP20/fisiologia , Condicionamento Físico Animal/fisiologia , Acidente Vascular Cerebral/prevenção & controle , Animais , Apoptose/fisiologia , Astrócitos/metabolismo , Astrócitos/fisiologia , Infarto Encefálico/fisiopatologia , Lobo Frontal/metabolismo , Proteínas de Choque Térmico HSP20/metabolismo , Ligadura , Masculino , Artéria Cerebral Média , Neuroglia/metabolismo , Neuroglia/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia
20.
Biomed Res Int ; 2015: 529580, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26413530

RESUMO

The purpose of this study was to compare the effect of PbtO2-guided therapy with traditional intracranial pressure- (ICP-) guided treatment on the management of cerebral variables, therapeutic interventions, survival rates, and neurological outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009 to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6 collaborative hospitals in northern Taiwan, excluding patients with severe systemic injuries, fixed and dilated pupils, and other major diseases. In total, 23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27 patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg) in the neurosurgical intensive care unit (NICU); demographic characteristics were similar across groups. The survival rate in the PbtO2-guided group was also significantly increased at 3 and 6 months after injury. Moreover, there was a significant correlation between the PbtO2 signal and Glasgow outcome scale-extended in patients from 1 to 6 months after injury. This finding demonstrates that therapy directed by PbtO2 monitoring is valuable for the treatment of patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be efficacious for preventing cerebral hypoxic events after brain trauma.


Assuntos
Química Encefálica/fisiologia , Lesões Encefálicas/terapia , Encéfalo/fisiologia , Oxigênio/análise , Adulto , Idoso , Lesões Encefálicas/mortalidade , Humanos , Pressão Intracraniana/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Taiwan , Resultado do Tratamento
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