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PURPOSE: To assess the Pediatric Vision Scanner (PVS), a handheld vision screening device designed to test for amblyopia and strabismus, in a general pediatric population. METHODS: In this prospective study, trained research staff screened 300 eligible children 24-72 months of age with no known eye conditions for amblyopia and strabismus using the PVS. A pediatric ophthalmologist masked to PVS screening results then performed a comprehensive eye examination. Sensitivity and specificity of the PVS was calculated with a 95% confidence interval. RESULTS: Based on the gold standard eye examination, 6 children (2%) had amblyopia and/or strabismus. The PVS detected all 6 cases, yielding a sensitivity rate of 100% (95% CI, 54%-100%). The PVS referred 45 additional children (15%) who had normal ophthalmic findings, yielding a specificity rate of 85% (95% CI, 80%-89%). The median acquisition time for the PVS was 28 seconds. CONCLUSIONS: The PVS detected amblyopia with high sensitivity in a nonenriched pediatric population. The device would allow children with amblyopia and/or strabismus to be referred to an eye care specialist as early as 2 years old. Given its short acquisition time, the PVS can be implemented in a pediatric clinic with minimal impact on workflow.
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Ambliopia , Erros de Refração , Estrabismo , Seleção Visual , Ambliopia/diagnóstico , Criança , Pré-Escolar , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Estrabismo/diagnósticoRESUMO
Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer's disease (AD). Although inflammation is present in both diseases, the exact mechanisms and crosslinks between periodontitis and AD are poorly understood. Therefore, this article aims to review possible comorbidity between periodontitis and AD. Here, the authors discuss the inflammatory aspects of periodontitis, how this oral condition produces a systemic inflammation and, finally, the contribution of this systemic inflammation for worsening neuroinflammation in the progression of AD.
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AIMS: To test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. METHODS: We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. RESULTS: Sodium-glucose co-transporter-2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319; P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. CONCLUSIONS: The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose , Disfunção Ventricular/tratamento farmacológico , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transportador 2 de Glucose-Sódio , Resultado do Tratamento , Disfunção Ventricular/etiologiaRESUMO
Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.
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Vacinas Anticâncer/uso terapêutico , Carcinoma de Células de Transição/terapia , Linfócitos T Citotóxicos/imunologia , Neoplasias da Bexiga Urinária/terapia , Idoso , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/uso terapêutico , Vacinas Anticâncer/imunologia , Intervalo Livre de Doença , Feminino , Antígeno HLA-A24/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVE: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. METHODS: We examined the antidiabetic effect of EPA in insulin receptor mutant (Insr(P1195L/+)) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. RESULTS: EPA supplementation was found to alleviate hyperglycemia of Insr(P1195L/+) mice fed HFD (Insr(P1195L/+)/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in Insr(P1195L/+) mice but not in wild-type mice, suggesting that Insr(P1195L/+) mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of Insr(P1195L/+) mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. CONCLUSIONS: EPA exerts an antidiabetic effect in Insr(P1195L/+)/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia.
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Adiponectina/deficiência , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica , Suplementos Nutricionais , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Hiperglicemia/tratamento farmacológico , Erros Inatos do Metabolismo/tratamento farmacológico , Adiponectina/metabolismo , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Hiperglicemia/complicações , Hiperglicemia/patologia , Masculino , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/patologia , Camundongos , Fosforilação/efeitos dos fármacosRESUMO
BACKGROUND/PURPOSE: Perceived age may be a better predictor of mortality rate than chronological age. We have demonstrated that perceived age was a significant biomarker for carotid atherosclerosis in Japanese. However, it remains to be determined which skin parameter is associated with atherosclerosis. The purpose of this study is to analyze the relationship between 10 facial skin-aging parameters and atherosclerosis in 169 middle-aged to elderly Japanese women who participated. METHODS: Facial photographs were taken under a shadowless lamp from three directions using a high-resolution digital camera. The digital images of each subject were analyzed using computer software and various parameters of skin aging such as pigmentation, wrinkles, and skin color were quantified. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. RESULTS: Facial pigmentation showed a significant correlation with carotid IMT, even after correction for age (r = 0.13, P = 0.03), and with visceral fat area. Stepwise regression analysis indicated that facial pigmentation was associated with carotid IMT via visceral fat area. CONCLUSION: Facial pigmentation may be a useful biomarker for carotid atherosclerosis in Japanese women.
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Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Face/patologia , Pigmentação da Pele , Pele/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Colorimetria/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Japão/epidemiologia , Pessoa de Meia-Idade , Fotografação/métodos , Prevalência , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIMS: Here we examined whether intellectual disability is independently associated with hyperglycaemia. METHODS: We recruited 233 consecutive young and middle-aged adults with intellectual disability. After exclusion of subjects on medication for metabolic diseases or with severe intellectual disability (IQ < 35), 121 subjects were divided by IQ into a group with moderate intellectual disability (35 ≤ IQ ≤ 50), a mild intellectual disability group (51 ≤ IQ ≤ 70) and a borderline group (IQ > 70). RESULTS: HbA1c level was higher in subjects with moderate intellectual disability (42 ± 9 mmol/mol; 6.0 ± 0.8%) than those in the borderline group (36 ± 4 mmol/mol; 5.5 ± 0.3%) and mild intellectual disability group (37 ± 5 mmol/mol; 5.5 ± 0.5%) groups. HbA1c level was correlated with age, BMI, blood pressure, serum triglycerides and IQ in simple linear regression analysis. Multiple regression analysis indicated that IQ, age, BMI and diastolic blood pressure were independent explanatory factors of HbA1c level. CONCLUSIONS: An unfavourable effect of intellectual disability on lifestyle and untoward effect of hyperglycaemia on cognitive function may underlie the association of low IQ with hyperglycaemia.
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Hemoglobinas Glicadas/metabolismo , Hiperglicemia/sangue , Deficiência Intelectual/sangue , Inteligência , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Testes de Inteligência , Masculino , Estudos Retrospectivos , Classe SocialRESUMO
BACKGROUND: Partner of SLD5 1 (PSF1) is an evolutionarily conserved DNA replication factor. Previous studies have suggested that transcriptional activity of the PSF1 gene correlated with malignancy of cancer cells. The objective of the current study was to evaluate the relationship between PSF1 expression and the clinical features of prostate cancer. METHODS: We determined the expression of PSF1 in 120 needle biopsy samples of prostate cancer by immunohistochemistry. We divided patients into PSF1-positive or -negative groups and analyzed the relationships between the expression of PSF1, the Gleason score, PSA level, TNM classification and prognosis. RESULTS: Our results showed that the PSF1 expression correlated significantly with PSA values at diagnosis (P=0.0028), with tumor grade (P<0.0001), and with clinical stage (P=0.0005). Moreover, the PSF1 expression correlated significantly with overall survival (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.17-15.8; P=0.003) and progression-free survival in 99 consecutive patients with prostate cancer. Noteworthy, the prognosis of PSF1-positive cases was also worse in patients with a Gleason score of 8-10 (HR 3.7; 95% CI 1.28-13.43; P=0.0143). Limitations include that this study had a retrospective design, that patients in the study were heterogeneous and included those with early and advanced cancer, and that small tumor fragments may not be representative of the entire carcinoma. CONCLUSIONS: PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis.
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Transportadores de Cassetes de Ligação de ATP/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Próstata/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
SUMMARY: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. INTRODUCTION: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. METHODS: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. RESULTS: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. CONCLUSIONS: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.
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Conservadores da Densidade Óssea/administração & dosagem , Denosumab/administração & dosagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Cálcio/uso terapêutico , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/prevenção & controle , Vitamina D/uso terapêuticoAssuntos
Anatomia/educação , Educação Médica/normas , Criança , Desenvolvimento Infantil , Humanos , JapãoRESUMO
BACKGROUND: It is known that periodontal ligament (PDL) harbors a heterogeneous progenitor cell population at different stages of lineage commitment. However, characterization of PDL stem cells committed to osteoblast/cementoblast (O/C) differentiation remains to be elucidated. The present study is carried out to isolate single cell-derived, cluster of differentiation (CD)105-positive PDL clones and to characterize the clones that present high potential to differentiate toward O/C phenotype in vitro. METHODS: Isolation of single cell-derived colonies (clones) from a CD105-enriched PDL progenitor cell population was performed by the ring-cloning technique. Cell clones were evaluated for their O/C differentiation potential, metabolic activity, and expression of STRO-1 protein. Additionally, the clones that showed potential to O/C differentiation were characterized by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for expression of runt-related transcriptor factor 2 (RUNX2), alkaline phosphatase, CD105, and CD166 during osteogenic induction. RESULTS: Six PDL-CD105(+) clones were obtained, three being highly O/C clones (C-O) and three others that did not have the ability to produce mineralized matrix in vitro (C-F). The C-O group showed lower metabolic activity compared with the C-F group, and both cell groups were positively immunostained for STRO-1. qRT-PCR analysis demonstrated an increased expression of transcripts for RUNX2 and CD166 during the maturation of C-O cells toward O/C phenotype. CONCLUSIONS: These results provide evidence that PDL-CD105(+) purified progenitor cells comprise a heterogeneous cell population that presents a cell subset with high O/C potential and, further, that surface antigen CD166 is modulated during the O/C maturation of this cell subset.
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Cemento Dentário/citologia , Células-Tronco Mesenquimais/fisiologia , Osteoblastos/citologia , Ligamento Periodontal/citologia , Fosfatase Alcalina/análise , Antígenos CD/análise , Antígenos de Superfície/análise , Adesão Celular/fisiologia , Moléculas de Adesão Celular Neuronais/análise , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Separação Celular , Células Clonais , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Cemento Dentário/metabolismo , Endoglina , Proteínas Fetais/análise , Humanos , Osteoblastos/metabolismo , Osteogênese/fisiologia , Fenótipo , Receptores de Superfície Celular/análiseRESUMO
Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P<0.0001; Pearsons correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.
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Doenças das Artérias Carótidas/genética , Polimorfismo de Nucleotídeo Único , Transaminases/genética , Adulto , Idoso , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
High fructose intake is associated with increased plasma triglyceride concentration, hepatic steatosis, impaired glucose tolerance, insulin resistance, and high blood pressure. In addition, increased fructose intake has recently been supposed to be a risk factor for dementia. However, direct effects of fructose on the brain function remain to be clarified. The localization of glucose transporter 5 (Glut5), a representative transporter of fructose, was immunohistochemically examined in the brains of humans, rats, and mice to clarify whether fructose was transported from the blood into the brain. Glut5 immunoreactivity was demonstrated to be located in the epithelial cells of the choroid plexus and the ependymal cells in the brains of humans and rats using commercial antibodies for Glut5. In addition, mRNA expression of mouse Glut5 was confirmed in the brains of mice. Immunohistochemical examination using a custom-made antibody against two regions of amino acid sequences of mouse Glut5 revealed that Glut5 immunoreactivity was also seen in the epithelial cells of the choroid plexus and the ependymal cells in the brains of mice. These findings show that Glut5 immunoreactivity is located in the epithelial cells of the choroid plexus and the ependymal cells, suggesting the possibility of the direct transportation of intravascular fructose into the brain parenchyma.
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Plexo Corióideo/química , Células Epiteliais/química , Transportador de Glucose Tipo 5/análise , Adulto , Idoso , Animais , Plexo Corióideo/metabolismo , Células Epiteliais/metabolismo , Feminino , Transportador de Glucose Tipo 5/genética , Transportador de Glucose Tipo 5/imunologia , Transportador de Glucose Tipo 5/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C3H , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos WKYRESUMO
BACKGROUND: We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese. METHODS: A total of 15,471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model. RESULTS: Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26-0.98) (P=0.043) and 0.46 (0.22-0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer. CONCLUSION: Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.
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Carotenoides , Dieta , Neoplasias da Próstata/dietoterapia , Verduras , Adulto , Idoso , Carotenoides/administração & dosagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/patologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: A recent genome-wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non-European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function. METHODS: Study subjects were 1190 general Japanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity (DSWMH), was evaluated by brain magnetic resonance imaging. RESULTS: A polymorphism rs3744028 was significantly associated with DSWMH grade (P = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B-type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH, association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function. CONCLUSION: Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes.
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Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/patologia , Cromossomos Humanos Par 17/genética , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Fibras Nervosas Mielinizadas/patologia , Idoso , Povo Asiático/genética , Povo Asiático/psicologia , Transtornos Cerebrovasculares/diagnóstico , Feminino , Humanos , Masculino , Neuroimagem/psicologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
In this paper, we propose a novel patient-specific method of modelling pulmonary airflow using graphics processing unit (GPU) computation that can be applied in medical practice. To overcome the barriers imposed by computation speed, installation price and footprint to the application of computational fluid dynamics, we focused on GPU computation and the lattice Boltzmann method (LBM). The GPU computation and LBM are compatible due to the characteristics of the GPU. As the optimisation of data access is essential for the performance of the GPU computation, we developed an adaptive meshing method, in which an airway model is covered by isotropic subdomains consisting of a uniform Cartesian mesh. We found that 4(3) size subdomains gave the best performance. The code was also tested on a small GPU cluster to confirm its performance and applicability, as the price and footprint are reasonable for medical applications.
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Simulação por Computador , Modelos Biológicos , Mecânica Respiratória/fisiologia , Gráficos por Computador , Humanos , Hidrodinâmica , Modelos Anatômicos , Sistema Respiratório/anatomia & histologiaRESUMO
We compared the effects of the Airway Scope(®) on haemodynamic responses during tracheal intubation with those of direct laryngoscopy in normotensive and hypertensive patients. The systolic blood pressure, diastolic blood pressures and heart rate were recorded: (a) before anaesthesia; (b) immediately before intubation; (c) at intubation; and (d) 1, 2, 3, 4 and 5 min after intubation. In normotensive patients, the increase in blood pressure and heart rate over time were significantly lower with the Airway Scope than with the Macintosh laryngoscope (p < 0.003). In hypertensive patients, however, there was no difference in the changes over time in any of these haemodynamic measures between the two devices (p > 0.05). We conclude that the Airway Scope attenuates haemodynamic responses to tracheal intubation in comparison with the laryngoscope in normotensive but not in hypertensive patients. You can respond to this article at http://www.anaesthesiacorrespondence.com.
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Hemodinâmica/fisiologia , Hipertensão/fisiopatologia , Intubação Intratraqueal/instrumentação , Laringoscópios , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Feminino , Glote/fisiologia , Frequência Cardíaca/fisiologia , Rouquidão/epidemiologia , Rouquidão/etiologia , Humanos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Faringite/epidemiologia , Faringite/etiologia , Complicações Pós-Operatórias/epidemiologia , Tamanho da Amostra , Adulto JovemRESUMO
Although several major histocompatibility complex (MHC)-wide single-nucleotide polymorphism (SNP) studies have been performed in populations of European descent, none have been performed in Asian populations. The objective of this study was to identify human leukocyte antigen (HLA) loci associated with multiple sclerosis (MS) in a Japanese population genotyped for 3534 MHC region SNPs. Using a logistic regression model, two SNPs (MHC Class III SNP rs422951 in the NOTCH4 gene and MHC Class II SNP rs3997849, susceptible alleles A and G, respectively) were independently associated with MS susceptibility (204 patients; 280 controls), two (MHC Class II SNP rs660895 and MHC Class I SNP rs2269704 in the NRM gene, susceptible alleles G and G, respectively) with aquaporin-4- (AQP4-) MS susceptibility (149 patients; 280 controls) and a single SNP (MHC Class II SNP rs1694112, susceptible allele G) was significant when contrasting AQP4+ against AQP4- patients. Haplotype analysis revealed a large susceptible association, likely DRB1*04 or a locus included in the DRB1*04 haplotype, with AQP4- MS, which excluded DRB1*15:01. This study is the largest study of the HLA's contribution to MS in Japanese individuals.
Assuntos
Antígenos HLA/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Japão , Masculino , FenótipoRESUMO
Three previous cohort studies in the USA reported that dairy product consumption was significantly associated with an increased risk of Parkinson's disease (PD) in men, but not in women. We examined the relationship between consumption of dairy products, calcium, and vitamin D and the risk of PD using data from a multicenter hospital-based case-control study in Japan. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, and dietary factors including cholesterol, dietary glycemic index, vitamin E, ß-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy product consumption was not materially associated with the risk of PD (P for trend = 0.62). No evident relationships were observed between intake of milk, yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59, and 0.35, respectively). There were no measurable associations between consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69, respectively). No significant interactions were observed between the dietary exposures and sex regarding PD. Our results suggest that intake of dairy products, calcium, and vitamin D was not related to PD, regardless of sex. However, such null relationships might be a consequence of PD.
Assuntos
Cálcio da Dieta/administração & dosagem , Cálcio/administração & dosagem , Laticínios , Doença de Parkinson/etnologia , Doença de Parkinson/etiologia , Vitamina D/administração & dosagem , Idoso , Cálcio/efeitos adversos , Cálcio da Dieta/efeitos adversos , Estudos de Casos e Controles , Laticínios/efeitos adversos , Feminino , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/efeitos adversosRESUMO
BACKGROUND: antioxidant vitamins are expected to protect cells from oxidative damage by neutralizing the effects of reactive oxygen species. However, epidemiological evidence regarding the associations between antioxidant vitamin intake and Parkinson's disease (PD) is limited and inconsistent. We investigated the relationship between dietary intake of selected antioxidant vitamins, vegetables and fruit and the risk of PD in Japan using data from a multicenter hospital-based case-control study. METHODS: included were 249 patients within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, dietary intake of cholesterol, alcohol, total dairy products, and coffee and the dietary glycemic index. RESULTS: higher consumption of vitamin E and ß-carotene was significantly associated with a reduced risk of PD after adjustment for confounders under study: the adjusted odds ratio in the highest quartile was 0.45 (95% confidence interval [CI]: 0.25-0.79, P for trend = 0.009) for vitamin E and 0.56 (95% CI: 0.33-0.97, P for trend = 0.03) for ß-carotene. Stratified by sex, such inverse associations were significant only in women. No material relationships were shown between intake of vitamin C, α-carotene, cryptoxanthin, green and yellow vegetables, other vegetables, or fruit and the risk of PD. CONCLUSIONS: higher intake of vitamin E and ß-carotene may be associated with a decreased risk of PD.