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1.
Acta Diabetol ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399781

RESUMO

BACKGROUND: The fluctuation of hemoglobin A1c (HbA1c) and changes in health habits over time was not considered in previous studies. The aim of this study was to evaluate the time-sequenced association between malignancy incidence and HbA1c with a longitudinal study design using repeated measurements of HbA1c. METHODS: A retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. All participants who underwent voluntary health check-ups at the hospital were included. Our outcomes were the development of malignancy. We compared these outcomes using HbA1c categories. Longitudinal analyses were conducted with a mixed effects model in which time-dependent HbA1c measurements were applied to consider fluctuations in HbA1c levels, adjusted for covariates. RESULTS: A total of 77,385 nondiabetic participants were included in the study; the mean age was 44.7 and 49.4% of participants were male. During a median follow-up of 1588 (interquartile range 730-2946) days, 4506 (5.8%) participants developed malignancies. The relationship between future malignancies and HbA1c was U-shaped; both the lower HbA1c groups (OR 1.31, 95% CI 1.17-1.46 for < 5.0%) and the higher HbA1c group (OR 1.87, 95% CI 1.03-3.39 for ≥ 7.5%) had significantly higher odds ratios compared to the 5.5-5.9%. The lowest HbA1c was associated with higher odds of breast cancer (OR 1.5, 95% CI 1.21-1.86) and female genital cancer (OR 1.57, 95% CI 1.04-2.37). CONCLUSIONS: Our study found a U-shaped association between HbA1c and future malignancies among nondiabetic people but did not find additional risk at the prediabetic level. Low HbA1c may be associated with the incidence of breast cancer and female genital cancer.

2.
J Diabetes Investig ; 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31074113

RESUMO

AIMS/INTRODUCTION: Osteoporosis is known to be intimately related to sympathetic nerve activity. We examined the relationship of plasma leptin with cortical and trabecular bone components in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: The present cross-sectional study included 182 type 2 diabetes mellitus patients (93 men, 89 women). Cortical thickness (CoTh) and trabecular bone mineral density (BMD) were determined at the 5.5% distal radius using an LD-100 ultrasonic bone densitometry device. Plasma leptin along with physical and laboratory measurements was simultaneously determined. RESULTS: Plasma leptin, but not body mass index (BMI), was inversely correlated with CoTh (ρ = -0.487, P < 0.001), while BMI, but not plasma leptin, was positively correlated with trabecular BMD (ρ = 0.369, P < 0.001). In multivariable regression analysis, after adjustments for age, sex, duration of diabetes, glycated hemoglobin A1c, albumin, estimated glomerular filtration rate, parathyroid hormone and handgrip strength, plasma leptin was inversely associated with CoTh (ß = -0.258, P < 0.001), but not trabecular BMD. Furthermore, plasma leptin level retained a significant association with CoTh after further adjustment for BMI (ß = -0.237, P < 0.001) and BMI plus waist-to-hip ratio (ß = -0.243, P < 0.001). In contrast, the "sex × leptin" interaction was not significant (P = 0.596). CONCLUSIONS: Leptin level in plasma, independent of BMI and BMI plus waist-to-hip ratio, was shown to be inversely associated with CoTh, but not trabecular BMD, suggesting that hyperleptinemia resulting from obesity might contribute to cortical porosis in patients with type 2 diabetes mellitus.

3.
J Nephrol ; 32(4): 595-603, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937855

RESUMO

BACKGROUND: The aim of this study was to evaluate whether angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) use prior to medical intensive care unit (ICU) admission was associated with in-hospital mortality and length of ICU stay. METHODS: A propensity score-matched cohort study was conducted at single center from 2004 to 2016. We included all adult patients who were admitted to the ICU due to internal medicine-related conditions. We compared patients who had used ACEIs/ARBs prior to ICU admission to patients who had not. Our primary and secondary outcomes were in-hospital mortality and length of stay among survivors and the deceased. Propensity scores were calculated via logistic regression analyses with forward stepwise selection. An odds ratio (OR) for primary outcome was calculated via logistic regression. Sensitivity analyses were performed using conditional logistic regression models including different sets of covariates to confirm our results. RESULTS: 3095 patients were admitted to the ICU. Overall, 693 patients were identified via matching, 231 of whom had used ACEIs/ARBs and 462 of whom had not. None of the baseline characteristics differed significantly between groups. Among them, 131 (18.9%) died. Those who had used ACEIs/ARBs had a lower rate of mortality (p < 0.01). Length of ICU stay did not differ significantly between those with ACEIs/ARBs and those without among survivors (p = 0.43) and the deceased (p = 0.14). The OR for mortality was 0.51 (95% confidence interval 0.32-0.79). The results of the sensitivity analyses confirmed the results (ORs 0.4 6-0.53; all were statistically significant). CONCLUSION: Prior ACEI/ARB use may be related to in-hospital mortality among medical ICU patients.

4.
Hypertens Res ; 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31019248

RESUMO

Based on the obesity paradox, people with a normal body mass index (BMI) may have a higher risk of mortality than those with a BMI that falls within the obese range. Despite the availability of other anthropometric measures, obesity is commonly evaluated based on BMI. A body shape index (ABSI) and body roundness index (BRI) have recently been proposed as new anthropometric measures that are calculated with height, weight, and waist circumference. This study investigated the associations between the traditional and new body composition indices and arterial stiffness using the brachial-ankle pulse wave velocity (baPWV). Overall, 3512 individuals (1228 men and 2284 women) were enrolled and were divided into two groups according to BMI. Multiple regression analysis was performed to assess the relationship between baPWV and body composition. baPWV was significantly associated with ABSI (ß = 0.087, p = 0.002), visceral adipose tissue (VAT; ß = 0.081, p = 0.002), and the visceral/subcutaneous adipose tissue (VAT/SAT) ratio (ß = 0.108, p < 0.001) in non-obese men. In non-obese women, baPWV was significantly associated with several variables but not the VAT/SAT ratio. Similarly, baPWV was significantly associated with BMI (ß = 0.103, p = 0.038), BRI (ß = 0.104, p = 0.036), VAT (ß = 0.167, p = 0.001), and the VAT/SAT ratio (ß = 0.106, p = 0.028) in obese women. ABSI can be used with high accuracy to evaluate fat distribution in non-obese men to predict arterial stiffness. However, the BRI should be used in addition to BMI to assess the body composition of women more accurately. ABSI and the BRI can be used to identify predictors of vascular remodeling or organic vascular dysfunction.

5.
J Alzheimers Dis ; 68(2): 735-744, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30883349

RESUMO

BACKGROUND: Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. OBJECTIVE: The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. METHODS: We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. RESULTS: An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). CONCLUSIONS: The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

6.
BMJ Open ; 9(3): e026268, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30850415

RESUMO

OBJECTIVES: Earthquakes are a distressing natural phenomenon that can disrupt normal health-related behaviours. The aim of this study was to investigate changes in alcohol consumption behaviours in the immediate aftermath of mild to moderate earthquakes. SETTING: This retrospective cohort study was conducted at a large academic hospital in Tokyo, Japan from April 2004 to March 2017. PARTICIPANTS: We included all adult patients presenting with acute alcohol intoxication in the emergency room. PRIMARY AND SECONDARY OUTCOME MEASURES: Our outcome was the number of such patients per 24 hours period comparing days with and without earthquake activity. We mainly focused on mild to moderate earthquakes (Shindo scale of less than 3). We conducted a simple generalised autoregressive conditional heteroscedasticity (GARCH) analysis, followed by a multivariate GARCH, including year-fixed effects and secular changes in alcohol taxation. Subanalyses were conducted by gender and age group. RESULTS: During the study period, 706 earthquakes were observed with a median Shindo scale of 2 (IQR: 1). During this period, 6395 patients were admitted with acute ethanol intoxication; the mean age was 42.6 (SD: 16.9) years and 4592 (71.8%) patients were male. In univariate analyses, the occurrence of daytime earthquakes was marginally inversely related to the number of acutely intoxicated patients (ß coefficient: -0.19, 95% CI -0.40 to 0.01). This finding remained similar in multivariate analyses after adjustment for covariates. In analyses stratified by gender, the inverse association between daytime earthquakes and alcohol intoxication was only observed among men (p<0.03 for males and p=0.99 for females). In subanalyses by age, older people were less likely to be admitted to the hospital due to acute alcohol intoxication on days with daytime earthquakes (p=0.11), but this was not the case for younger people (p=0.36). CONCLUSION: On days when a mild to moderate daytime earthquake occurred, the number of patients with acute alcohol intoxication was lower compared with days without earthquakes. Even milder forms of potentially catastrophic events appear to influence social behaviour; mild to moderate earthquake activity is associated with the avoidance of excessive alcohol consumption.

7.
Sleep ; 42(6)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30810208

RESUMO

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

8.
Endocr Connect ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508417

RESUMO

BACKGROUND: The aim of this study was to evaluate the difference in malignancy incidence by evaluating time-dependent HbA1c levels among diabetic patients in a longitudinal study. METHODS: We conducted a retrospective longitudinal study at large academic hospital, Tokyo, Japan, from 2006 to 2016. We included all diabetic patients who were 50 years or older and who underwent health check-ups at the center for preventive medicine. Those patients with a prior history of malignancies were excluded. We categorized patients into 5 groups on the basis of HbA1c measurements: <5.4%, 5.5-6.4%, 6.5-7.4%, 7.5-8.5%, >8.5%. Our primary outcome was the development of any types of malignancy. Longitudinal analyses by a mixed effect model with time-dependent HbA1c levels were applied in order to take into account fluctuations in HbA1c levels within the same patient. RESULTS: In total, 2,729 participants were included in this study, where the mean age was 62.6(standard deviation(SD):7.8) and 2,031(74.4%) were male. The mean disease duration of diabetes was 7.6(SD:7.6) years, and 1,688(61.8%) were prescribed medications. Median follow-up was 1,443.5(Interquartile range (IQR):2,508) days, and 376(13.8%) developed malignancies. Compared to the reference range of HbA1c(5.5-6.4%), the odds ratios for developing malignancies among the other HbA1c level groups were similar and not statistically different[OR:0.98,95%CI:0.31-3.15(for HbA1c<5.4%);OR:0.88,95%CI:0.69-1.12(for HbA1c 6.5-7.4%);OR:0.88,95%CI:0.64-1.22(for HbA1c 7.5-8.4%);OR1.07,95%CI:0.70-1.66(for HbA1c >8.5%)]. CONCLUSION: In our study, there was no association between glycemic control and the development of future malignancies. Compared to very strictly controlled HbA1c levels, both excessive control and good or bad control had a statistically similar risk of developing malignancies.

9.
Med Sci Sports Exerc ; 50(12): 2433-2441, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30102679

RESUMO

PURPOSE: Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. METHODS: We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. RESULTS: We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. CONCLUSIONS: We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

10.
Nephrology (Carlton) ; 2018 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-30146708

RESUMO

Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies (GWAS) have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11,283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort (J-MICC) Study sites. Individual GRS was constructed combining 18 single nucleotide polymorphisms (SNP) identified in a Japanese population. Participants with eGFR <60 mL/min/1.73 m2 was defined as case (stage 3 CKD or higher) in this study. Logistic regression analysis was used to examine the association between the GRS and CKD risk with adjustment for sex, age, hypertension, and type 2 diabetes mellitus. The frequency of individuals with CKD was 8.3%, which was relatively low compared with those previously reported in a Japanese population. The odds ratio of having CKD was 1.120 (95% confidence interval: 1.042-1.203) per 10 GRS increment in the fully adjusted model (P = 0.002). The C-statistic was significantly increased in the model with the GRS, comparing with the model without the GRS (0.720 vs. 0.719, Pdifference = 0.008). Increment of the GRS was associated with increased risk of CKD. Additionally, the GRS significantly improved the discriminatory ability of CKD prevalence in a Japanese population; however, the improvement of discriminatory ability brought about by the GRS seemed to be small compared with that of non-genetic CKD risk factors. This article is protected by copyright. All rights reserved.

11.
Sci Rep ; 8(1): 10767, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018407

RESUMO

LD-100, a quantitative ultrasonic device, allows us to measure cortical thickness (CoTh). Patients with type 2 diabetes mellitus (T2DM) show high prevalence of sarcopenia. This study aimed to clarify the association of handgrip strength (HGS) with cortical porosis, a major risk for fracture of DM. CoTh and trabecular bone mineral density (TrBMD) at the 5.5% distal radius were assessed in T2DM female patients (n = 122) and non-DM female controls (n = 704) by LD-100. T2DM patients aged older 40 years showed significantly lower HGS and CoTh, but not TrBMD, than non-DM counterparts. Although HGS was significantly and positively correlated with CoTh and TrBMD in T2DM patients, multivariate analysis revealed HGS as an independent factor positively associated with CoTh, but not TrBMD, in T2DM patients, suggesting the preferential association of HGS with cortical, but not trabecular, bone component in T2DM female patients. In conclusion, the present study demonstrated an early decline of HGS in T2DM female patients as compared with non-DM healthy controls after the age of 40 years, which is independently associated with thinner CoTh, but not TrBMD in T2DM patients, and thus suggested that reduced muscle strength associated with DM might be a major factor for cortical porosis development in DM patients.

12.
Int J Rheum Dis ; 21(6): 1314-1321, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29879315

RESUMO

BACKGROUND: The hypothesis that patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) have a high risk for future cardiovascular diseases has not been adequately tested. The aim of this study is to evaluate this hypothesis in Japan, where the prevalence and severity of PMR and GCA are the lowest. METHODS: A propensity score matched cohort study was conducted at St. Luke's International Hospital, Tokyo, Japan, from 2003 to 2016. We included all patients who were diagnosed as PMR or GCA cases and matched comparators with a proportion of 1 : 2. Our primary outcome was newly diagnosed cardiovascular disease. The propensity score was calculated using logistic regression with forward stepwise selection in 30 variables. Kaplan-Meier curves were drawn and the log-rank test and Cox proportional hazard model were performed for survival analyses. Two types of sensitivity analyses were conducted to confirm the results. RESULTS: Among 2461 potential patients, the propensity score identified 504 (168 cases and 336 comparators) patients. During follow up (median 839.5 days), 110 (21.8%) developed cardiovascular diseases. The Kaplan-Meier curves between those with and without PMR or GCA were not significantly different (P = 0.85). The Cox proportional hazard model calculated the hazard ratio (HR) of those with PMR or GCA compared to those without as 0.96 (95% CI: 0.64-1.46). The results from sensitivity analyses were consistent (HR 0.70-1.06). CONCLUSION: Patients with PMR or GCA may not have a higher risk of future cardiovascular diseases among the Japanese population. The sensitivity analyses and sample size calculation supported the results.


Assuntos
Doenças Cardiovasculares/epidemiologia , Arterite de Células Gigantes/epidemiologia , Polimialgia Reumática/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Distribuição de Qui-Quadrado , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/diagnóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tóquio/epidemiologia
13.
Front Neurol ; 9: 421, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29942280

RESUMO

Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan. Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as "improved," while the remaining patients were classified as "non-improved." In the shunt intervention (n = 437) and non-shunt intervention (n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U-test. Finally, we examined subjects in the shunt intervention group (n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt (n = 540). Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31-0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference. Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective.

14.
J Neurosurg ; : 1-8, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29547088

RESUMO

OBJECTIVE The gold standard for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is the CSF removal test. For elderly patients, however, a less invasive diagnostic method is required. On MRI, high-convexity tightness was reported to be an important finding for the diagnosis of iNPH. On SPECT, patients with iNPH often show hyperperfusion of the high-convexity area. The authors tested 2 hypotheses regarding the SPECT finding: 1) it is relative hyperperfusion reflecting the increased gray matter density of the convexity, and 2) it is useful for the diagnosis of iNPH. The authors termed the SPECT finding the convexity apparent hyperperfusion (CAPPAH) sign. METHODS Two clinical studies were conducted. In study 1, SPECT was performed for 20 patients suspected of having iNPH, and regional cerebral blood flow (rCBF) of the high-convexity area was examined using quantitative analysis. Clinical differences between patients with the CAPPAH sign (CAP) and those without it (NCAP) were also compared. In study 2, the CAPPAH sign was retrospectively assessed in 30 patients with iNPH and 19 healthy controls using SPECT images and 3D stereotactic surface projection. RESULTS In study 1, rCBF of the high-convexity area of the CAP group was calculated as 35.2-43.7 ml/min/100 g, which is not higher than normal values of rCBF determined by SPECT. The NCAP group showed lower cognitive function and weaker responses to the removal of CSF than the CAP group. In study 2, the CAPPAH sign was positive only in patients with iNPH (24/30) and not in controls (sensitivity 80%, specificity 100%). The coincidence rate between tight high convexity on MRI and the CAPPAH sign was very high (28/30). CONCLUSIONS Patients with iNPH showed hyperperfusion of the high-convexity area on SPECT; however, the presence of the CAPPAH sign did not indicate real hyperperfusion of rCBF in the high-convexity area. The authors speculated that patients with iNPH without the CAPPAH sign, despite showing tight high convexity on MRI, might have comorbidities such as Alzheimer's disease.

15.
World Neurosurg ; 113: e77-e81, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29421448

RESUMO

BACKGROUND: Among human oral bacteria, particular kinds of Streptococcus mutans (SM) known as dental caries pathogens contain a collagen-binding protein, Cnm, and show platelet aggregation inhibition and matrix metalloproteinase-9 activation. We have previously reported that these strains may be a risk factor for intracerebral hemorrhage. As a major sample-providing hospital, we report the clinical details, including intracranial aneurysms and ischemic stroke. METHODS: After the study received approval from the Ethical Committee, 429 samples of whole saliva were obtained from patients who were admitted to or visited our hospital between February 16, 2010, and February 28, 2011. The study cohort comprised 48 patients with cardioembolic stroke (CES), 151 with non-CES infarct, 54 with intracerebral hemorrhage (ICH), 43 with ruptured intracranial aneurysm (RIA), and 97 with unruptured intracranial aneurysm (UIA). Cultured SM was identified as Cnm-positive when the corresponding gene was positive. The results were compared with those from 79 healthy volunteers. Relationships between Cnm-positive SM and known risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, were analyzed. RESULTS: A statistically significant high Cnm-positive rate was observed in patients with CES, non-CES infarct, ICH, and RIA (P = 0.002, 0.039, 0.013, and 0.009, respectively). There were no relationships between Cnm-positive SM and known risk factors. CONCLUSIONS: Specific types of oral SM can be a risk factor for cardioembolic infarct, intracerebral hemorrhage, and intracranial aneurysm rupture. Further study is needed.


Assuntos
Adesinas Bacterianas/efeitos adversos , Proteínas de Transporte/efeitos adversos , Saliva/microbiologia , Streptococcus mutans/patogenicidade , Acidente Vascular Cerebral/etiologia , Adesinas Bacterianas/análise , Adesinas Bacterianas/genética , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Aneurisma Roto/epidemiologia , Aneurisma Roto/etiologia , Fibrilação Atrial/complicações , Proteínas de Transporte/análise , Proteínas de Transporte/genética , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Comorbidade , Cárie Dentária/complicações , Cárie Dentária/microbiologia , Diabetes Mellitus/epidemiologia , Suscetibilidade a Doenças , Feminino , Genes Bacterianos , Cardiopatias/complicações , Cardiopatias/epidemiologia , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/etiologia , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/etiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Streptococcus mutans/genética , Streptococcus mutans/metabolismo , Acidente Vascular Cerebral/epidemiologia
16.
Sci Rep ; 8(1): 1493, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29367735

RESUMO

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

18.
Sci Rep ; 8(1): 82, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29311711

RESUMO

We investigated whether the phosphate (Pi) load in the circulation causes renal damage in non-CKD women. This cross-sectional study included 1,094 non-CKD Japanese women. Fibroblast growth factor (FGF)-23 as a parameter for the Pi load, bone alkaline phosphatase (BAP) as a bone metabolic marker, and the urinary albumin-to-creatinine ratio (UACR) as an early marker for renal damage were measured. Postmenopausal women exhibited significantly higher levels of serum Pi, FGF-23, BAP, and UACR and significantly lower eGFR than premenopausal women. In postmenopausal women, a multiple regression analysis confirmed a correlation between serum BAP and log UACR. In premenopausal women, although serum FGF-23 did not correlate with log UACR, a multiple regression analysis revealed that FGF-23 correlated with log UACR. Based on the i ncrease observed in BAP and its close relationship with log UACR in postmenopausal women, the release of Pi from bone may be linked to the systemic circulation of Pi, which has the potential to induce renal and vascular damage. Therefore, serum FGF-23 may be a useful marker for renal and vascular damage in premenopausal women; however, it currently remains unclear whether FGF-23 by itself or as a surrogate marker for the Pi load induces damage in the kidney and/or vasculature.


Assuntos
Albuminas/metabolismo , Albuminúria/urina , Fosfatase Alcalina/metabolismo , Osso e Ossos/enzimologia , Pós-Menopausa/metabolismo , Adulto , Fosfatase Alcalina/urina , Biomarcadores , Comorbidade , Feminino , Taxa de Filtração Glomerular , Humanos , Japão , Pessoa de Meia-Idade , Razão de Chances , Pós-Menopausa/urina , Pré-Menopausa , Vigilância em Saúde Pública
19.
J Alzheimers Dis ; 61(1): 145-155, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29154273

RESUMO

BACKGROUND: The anti-aging protein, α-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α-Klotho in the brain has not been sufficiently investigated. OBJECTIVE: Here, we investigated the association between α-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). METHODS: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α-Klotho level were retrospectively investigated. RESULTS: The α-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the α-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low α-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. CONCLUSION: A reduced blood α-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α-Klotho level may serve as a useful clinical index of vascular cognitive impairment.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Glucuronidase/sangue , Leucoencefalopatias/complicações , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagem , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Índice de Gravidade de Doença
20.
J Epidemiol ; 28(4): 185-193, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29176272

RESUMO

BACKGROUND: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. METHODS: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. RESULTS: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was -2.49 mg/dL (95% confidence interval [CI], -3.85 to -1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (-3.24 mg/dL, 95% CI, -5.03 to -1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. CONCLUSIONS: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Lipoproteínas LDL/sangue , Polimorfismo Genético/genética , Triglicerídeos/sangue , Adulto , Idoso , Alelos , Estudos de Coortes , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade
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