International Clinical Research Center

Czech Republic

International Clinical Research Center

Czech Republic
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Geda Y.E.,International Clinical Research Center | Nedelska Z.,Mayo Medical School | Nedelska Z.,International Clinical Research Center
American Journal of Geriatric Psychiatry | Year: 2012

The field of aging and dementia is increasingly preoccupied with identification of the asymptomatic phenotype of Alzheimer disease (AD). A quick glance at historical landmarks in the field indicates that the agenda and priorities of the field have evolved over time. The initial focus of research was dementia. In the late 1980s and 1990s, dementia researchers reported that some elderly persons are neither demented nor cognitively normal. Experts coined various terms to describe the gray zone between normal cognitive aging and dementia, including mild cognitive impairment. Advances made in epidemiologic, neuroimaging, and biomarkers research emboldened the field to seriously pursue the avenue of identifying asymptomatic AD. Accurate "diagnosis" of the phenotype has also evolved over time. For example, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Task Force is contemplating to use the terms major and minor neurocognitive disorders. The six papers published in this edition of the journal pertain to mild cognitive impairment, which is envisaged to become a subset of minor neurocognitive disorders. These six studies have three points in common: 1) All of them are observational studies; 2) they have generated useful hypotheses or made important observations without necessarily relying on expensive biomarkers; and 3) Based on the new National Institute on Aging and the Alzheimer's Association guidelines, all the studies addressed the symptomatic phase of AD. Questionnaire-based observational studies will continue to be useful until such a time that validated biomarkers, be it chemical or neuroimaging, become widely available and reasonably affordable. © 2012 American Association for Geriatric Psychiatry.


Eshak E.S.,Osaka University | Eshak E.S.,Menoufia University | Iso H.,Osaka University | Mizoue T.,International Clinical Research Center | And 3 more authors.
Clinical Nutrition | Year: 2013

Background & aims: Japan has experienced a jump in the diabetes prevalence rates. We want to examine whether increased intake of soft drink and juices have contributed to this jump. Methods: Participants were 27,585 Japanese men and women aged 40-59 years who had no prior history of diabetes. Intakes of soft drink, 100% fruit juice and vegetable juice were measured by a validated food frequency questionnaire. Odds ratios of type 2 diabetes over 5 and 10 years were estimated by using logistic regression. Results: A total of 484 men and 340 women reported newly diagnosed diabetes during10 years. High soft drink intake was associated with increased risk of type 2 diabetes in women but not men; odds ratio (95% CI) for women with almost daily consumption versus non-consumers was 2.10 (1.23-3.59; P-trend = 0.004) and 1.79 (1.11-2.89; P-trend = 0.01) at 5 and 10 years, respectively. The association was evident in overweight, highly educated and premenopausal women, and women with blue collar job. Intakes of 100% fruit juice and vegetable juice were not associated with risk of type 2 diabetes for either gender (P-trend >0.05). Conclusions: Soft drink but not pure juices consumption was associated with increased risk of type 2 diabetes in Japanese women. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.


Nanri A.,International Clinical Research Center | Mizoue T.,International Clinical Research Center | Noda M.,National Center for Global Health and Medicine | Takahashi Y.,National Center for Global Health and Medicine | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2010

Background: Refined carbohydrates have been suggested to deteriorate glucose metabolism; however, whether persons with elevated intakes of white rice, which is a major staple food for the Japanese, experience increased risk of developing type 2 diabetes remains unclear. Objective: We prospectively investigated the association between white rice intake and risk of type 2 diabetes. Design: Participants were 25,666 men and 33,622 women aged 45-75 y who participated in the second survey of the Japan Public Health Center-based Prospective Study and who had no prior history of diabetes. We ascertained food intake by using a validated 147-item food-frequency questionnaire. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over 5 y were estimated by using logistic regressions. Results: A total of 1103 new cases of type 2 diabetes were self-reported. There was a significant association between rice intake and an increased risk of type 2 diabetes in women; the multivariate-adjusted odds ratio for the highest compared with lowest quartiles of rice intake was 1.65 (95% CI: 1.06, 2.57; P for trend = 0.005). In men, the association was unclear, although there was a suggestion of a positive association in persons who were not engaged in strenuous physical activity (P for trend = 0.08). Conclusions: Elevated intake of white rice is associated with an increased risk of type 2 diabetes in Japanese women. The finding that is suggestive of a positive association of rice intake in physically inactive men deserves further investigation. © 2010 American Society for Nutrition.


Nanri A.,International Clinical Research Center | Mizoue T.,International Clinical Research Center | Noda M.,National Center for Global Health and Medicine | Takahashi Y.,National Center for Global Health and Medicine | And 6 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Although fish intake can improve glucose metabolism, results of some prospective studies in Western populations suggest potential adverse effects of environmental contaminants in fish on type 2 diabetes risk. However, data from populations with high fish consumption are scarce. Objective: We prospectively investigated the association between fish intake and type 2 diabetes risk in Japanese adults. Design: The participants were 22,921 men and 29,759 women aged 45-75 y who completed a questionnaire of the second survey for the Japan Public Health Center-based Prospective Study and who had no history of diabetes. Diet was ascertained by using a 147-item food-frequency questionnaire. ORs of self-reported, physician-diagnosed type 2 diabetes over 5 y were estimated by using logistic regression. Results: During the 5-y period, 971 new cases (572 men and 399 women) of type 2 diabetes were self-reported. In men, fish intake was significantly associated with a decreased risk of type 2 diabetes; multivariable-adjusted ORs of type 2 diabetes for the highest compared with the lowest quartile of intake were 0.73 (95% CI: 0.54, 1.00; P-trend = 0.04) for total fish and seafood and 0.68 (95% CI: 0.50, 0.92; P-trend = 0.016) for small and medium fish (horse mackerel and sardine, saury and mackerel, and eel). Additional analysis by fat content of fish did not detect any significant association for each category. In women, fish intake was not appreciably associated with type 2 diabetes risk. Conclusion: In a population with high fish and seafood intake, fish consumption was associated with a lower risk of type 2 diabetes in men but not in women. © 2011 American Society for Nutrition.


Matsuo K.,Aichi Cancer Center Research Institute | Mizoue T.,International Clinical Research Center | Tanaka K.,Saga University | Tsuji I.,Tohoku University | And 7 more authors.
Annals of Oncology | Year: 2012

Background: Obesity has been recognized as important risk factors for colorectal cancer. However, limited evidence is available on colorectal cancer and body mass index (BMI) in Asian population. Methods: We conducted a pooled analysis of eight population-based prospective cohorts studies in Japan with more than 300 000 subjects to evaluate an impact of obesity in terms of BMI on colorectal cancer risk with unified categories. We estimated summary hazard ratio (HR) by pooling of study-specific HR for BMI categories with random effect model. Results: We found a significant positive association between BMI and colorectal cancer risk in male and female. Adjusted HRs for 1 kg/m 2 increase were 1.03 [95% confidence interval (CI) 1.02-1.04] for males and 1.02 (95% CI 1.00-1.03) for females. The association was stronger in colon, especially in proximal colon, relative to rectum. Males showed a stronger association than females. Population attributable fraction for colorectal cancer by BMI ≥25 kg/m 2 was 3.62% (95% CI 1.91-5.30) for males and 2.62% (95% CI 0.74-4.47) for females. Conclusions: We found significant association between BMI and colorectal cancer risk by pooling of data from cohort studies with considerable number of subjects among Japanese population. This information is important in cancer control planning, especially in Asian population. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Calvin A.D.,Rochester College | Carter R.E.,Mayo Medical School | Adachi T.,Showa University | MacEdo P.G.,University Brazilia | And 8 more authors.
Chest | Year: 2013

Background: Epidemiologic studies link short sleep duration to obesity and weight gain. Insuffi- cient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Methods: We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Results: Caloric intake in the sleep-restricted group increased by + 559 kcal/d (SD, 706 kcal/d, P = .006) and decreased in the control group by - 118 kcal/d (SD, 386 kcal/d, P = .51) for a net change of + 677 kcal/d (95% CI, 148-1,206 kcal/d; P = .014). Sleep restriction was not associated with changes in activity energy expenditure (P = .62). No change was seen in levels of leptin (P = .27) or ghrelin (P = .21). Conclusions: Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. © 2013 American College of Chest Physicians.


Helan M.,Mayo Medical School | Helan M.,International Clinical Research Center | Helan M.,Masaryk University | Aravamudan B.,Mayo Medical School | And 5 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2014

Within human pulmonary artery, neurotrophin growth factors [NTs; e.g. brain-derived neurotrophic factor (BDNF)] and their high-affinity receptors (tropomyosin-related kinase; Trk) and low-affinity receptors p75 neurotrophin receptor (p75NTR) have been reported, but their functional role is incompletely understood. We tested the hypothesis that BDNF is produced by human pulmonary artery endothelial cells (PAECs). In the context of hypoxia as a risk factor for pulmonary hypertension, we examined the effect of hypoxia on BDNF secretion and consequent autocrine effects on pulmonary endothelium. Initial ELISA analysis of circulating BDNF in 30 healthy human volunteers showed that 72h exposure to high altitude (~11,000ft, alveolar PO2=100mmHg) results in higher BDNF compared to samples taken at sea level. Separately, in human PAECs exposed for 24h to normoxia vs. hypoxia (1-3% O2), ELISA of extracellular media showed increased BDNF levels. Furthermore, quantitative PCR of PAECs showed 3-fold enhancement of BDNF gene transcription with hypoxia. In PAECs, BDNF induced NO production (measured using an NO-sensitive fluorescent dye DAF2-DA) that was significantly higher under hypoxic conditions, an effect also noted with the TrkB agonist 7,8-DHF. Importantly, hypoxia-induced NO was blunted by neutralization of secreted BDNF using the chimeric TrkB-Fc. Both hypoxia and BDNF increased iNOS (but not eNOS) mRNA expression. In accordance, BDNF enhancement of NO in hypoxia was not blunted by 50nM l-NAME (eNOS inhibition) but substantially lower with 100μM l-NAME (eNOS and iNOS inhibition). Hypoxia and BDNF also induced expression of hypoxia inducible factor 1 alpha (HIF-1α), a subunit of the transcription factor HIF-1, and pharmacological inhibition of HIF-1 diminished hypoxia effects on BDNF expression and secretion, and NO production. These results indicate that human PAECs express and secrete BDNF in response to hypoxia via a HIF-1-regulated pathway. © 2014 Elsevier Ltd.


Nanri A.,International Clinical Research Center | Kimura Y.,Fukuyama University | Matsushita Y.,International Clinical Research Center | Ohta M.,University of Occupational and Environmental Health Japan | And 4 more authors.
European Journal of Clinical Nutrition | Year: 2010

Objective: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. Methods: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D 16) with adjustment for potential confounding variables. Results: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend0.006). Other dietary patterns were not appreciably associated with depressive symptoms. Conclusions: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status. © 2010 Macmillan Publishers Limited All rights reserved.


Kimura Y.,Fukuyama University | Sato M.,Kyushu University | Kurotani K.,International Clinical Research Center | Nanri A.,International Clinical Research Center | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: PUFAs are susceptible to lipid peroxidation and play a role in inflammation, both of which can induce oxidative stress. However, the relation of PUFA to oxidative DNA damage in humans is elusive. Objective: We examined the association between concentrations of circulatory PUFAs and urinary 8-oxo-7,8-dihydroguanine (8-oxoGua) in Japanese men and women. Design: The subjects were 495 participants (290 men and 205 women) in a cross-sectional study in 2 municipal offices in Japan. Serum cholesterol ester (CE) and phospholipid fatty acid composition were measured by gas-liquid chromatography. Urinary 8-oxoGua concentrations were measured by HPLC, and 8-oxoGua values for each tertile of PUFA after adjustment for covariates were calculated by multiple regression. Results: Urinary 8-oxoGua concentrations increased with increasing concentrations of n-3 (omega-3) PUFAs, EPA, and DHA in serum CE (P-trend = 0.001, 0.01, and 0.009, respectively), whereas they decreased with increasing concentrations of n-6 PUFAs and linoleic acid (P-trend = 0.02 and 0.051, respectively). Conclusion: Oxidative DNA damage may be greater with higher concentrations of long-chain n-3 PUFAs but lower with higher concentrations of n-6 (omega-6) PUFAs. © 2012 American Society for Nutrition.


Poudel-Tandukar K.,Waseda University | Sato M.,Kyushu University | Ejima Y.,Kyushu University | Nanri A.,International Clinical Research Center | And 3 more authors.
Atherosclerosis | Year: 2012

Background: Although fatty acid composition in serum and desaturase activity, which alters serum fatty acid composition, has been associated with C-reactive protein (CRP) concentration in Western populations, no study has been carried out in non-Western populations. We examined the association of serum fatty acids and estimated desaturase activity with CRP concentrations in Japanese men and women. Methods: Subjects were 489 Japanese municipal employees aged 21-67 years who participated in a survey at the time of a periodic health check-up. Serum high-sensitivity CRP concentrations were measured using the latex agglutination nephelometry method. Fatty acid composition was measured in serum cholesteryl esters and desaturase activities by fatty acid product-to-precursor ratios. Relationships were assessed using multiple regression. Results: Serum CRP concentration was positively associated with palmitic acid (P for trend = 0.002) and inversely with alpha-linolenic acid (P for trend = 0.01) in men, and positively with dihomo-gamma-linolenic acid (P for trend in men or women = 0.01) and inversely with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women = 0.05 and 0.002, respectively) in men and women. Conclusions: Low-grade inflammation may be associated with a serum fatty acid pattern of high palmitic acid or low alpha-linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5-desaturase in both sexes. © 2011 Elsevier Ireland Ltd.

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