Publications by authors named "Nagato Kuriyama"

100 Publications

Genome-wide association study of serum prostate-specific antigen levels based on 1000 Genomes imputed data in Japanese: the Japan Multi-Institutional Collaborative Cohort Study.

Nagoya J Med Sci 2021 Feb;83(1):183-194

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance ( <5×10), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance ( <1×10). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.
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http://dx.doi.org/10.18999/nagjms.83.1.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938099PMC
February 2021

A genome-wide association study on confection consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort Study.

Br J Nutr 2021 Feb 26:1-9. Epub 2021 Feb 26.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.
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http://dx.doi.org/10.1017/S0007114521000684DOI Listing
February 2021

Assessing the relationship between high-sensitivity C-reactive protein and kidney function employing mendelian randomization in a Japanese community based J-MICC Study.

J Epidemiol 2021 Feb 20. Epub 2021 Feb 20.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine.

Background: Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches.

Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IV and IV, based on SNPs previously identified in European and Asian populations. IV and IV explained 3.4% and 3.9% of the variation in hs-CRP, respectively.

Results: Using the IV, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, -0.019 to 0.020 and -0.003, -0.019 to 0.014). For IV, we found similar results using the IVW and the WM methods (estimate, 95% CI: -0.005, -0.020 to 0.010 and -0.004, -0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IV: -0.008, -0.058 to 0.042; IV: 0.001, -0.036 to 0.036).

Conclusions: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
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http://dx.doi.org/10.2188/jea.JE20200540DOI Listing
February 2021

A 10-year longitudinal study of deep white matter lesions on magnetic resonance imaging.

Neuroradiology 2021 Feb 18. Epub 2021 Feb 18.

Department of Neurology, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto-shi, Kyoto-fu, 602-8566, Japan.

Purpose: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs.

Methods: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment.

Results: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment.

Conclusion: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.
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http://dx.doi.org/10.1007/s00234-020-02626-2DOI Listing
February 2021

Hip fractures among the elderly in Kyoto, Japan: a 10-year study.

Arch Osteoporos 2021 02 12;16(1):30. Epub 2021 Feb 12.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

In Kyoto Prefecture, Japan, the number of hip fractures increased during 2013-2017 compared to 2008-2012. However, the estimated overall incidence rate increased only in femoral neck fractures in men aged ≥75 and women aged ≥85.

Purpose: The incidence rate of hip fractures in Japan has plateaued or decreased. We investigated the annual hip fracture occurrences in Kyoto Prefecture, Japan, from 2008 to 2017.

Methods: Patients aged 65 years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The total number of beds in these institutions was 3701, accounting for 21.5% of the 17,242 acute-care beds in Kyoto Prefecture. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015.

Results: The total number of hip fractures was 10,060, with 47.5% femoral neck fractures and 52.5% trochanteric fractures. A decrease in number was seen only in trochanteric fractures in the group of 75- to 84-year-old women. The population-adjusted numbers of femoral neck fractures showed a significant increase in all age groups in men, whereas in women, there was an increase in femoral neck fractures in the ≥85 group and trochanteric fractures in the age group 65-74, and a decrease in trochanteric fractures in the age group 75-84. The estimated change in incidence rate showed an increase in femoral neck fractures in men aged ≥75 and women aged ≥85.

Conclusion: In Kyoto Prefecture, the number of hip fractures increased in the second half of the study period (2013-2017) compared to the first half (2008-2012). However, the incidence rate had not increased, except in femoral neck fractures in men aged ≥75 and women aged ≥85.
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http://dx.doi.org/10.1007/s11657-021-00888-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880939PMC
February 2021

Assessing the Relationship between and Chronic Kidney Disease.

Healthcare (Basel) 2021 Feb 3;9(2). Epub 2021 Feb 3.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

The relationship between infection and/or gastric disorders and chronic kidney disease (CKD) has not been elucidated. We investigated the relationship between and/or atrophic gastritis (AG) and chronic kidney disease. In total, 3560 participants (1127 men and 2433 women) were eligible for this cross-sectional study. We divided participants into four study groups: with/without infection and with/without AG. The HP (+) AG (-) group demonstrated a significant association with CKD compared with the HP (-) AG (-) group (adjusted odds ratio, 1.443; 95% confidence interval, 1.047-1.989). In contrast, the HP (+) AG (+) group showed significantly lower adjusted odds of CKD than the HP (-) AG (-) group (adjusted odds ratio, 0.608; 95% confidence interval, 0.402-0.920). infection without AG might be associated with CKD in these participants. Conversely, the HP (+) AG (+) group had lower odds of CKD. Uncovering an association between gastric and renal conditions could lead to development of new treatment strategies.
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http://dx.doi.org/10.3390/healthcare9020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913305PMC
February 2021

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

Neurol Med Chir (Tokyo) 2021 Feb 15;61(2):63-97. Epub 2021 Jan 15.

Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
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http://dx.doi.org/10.2176/nmc.st.2020-0292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905302PMC
February 2021

Mid-regional pro-adrenomedullin is a novel biomarker for arterial stiffness as the criterion for vascular failure in a cross-sectional study.

Sci Rep 2021 Jan 11;11(1):305. Epub 2021 Jan 11.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.
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http://dx.doi.org/10.1038/s41598-020-79525-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801498PMC
January 2021

The Association of Daily Physical Activity Behaviors with Visceral Fat.

Obes Res Clin Pract 2020 Nov - Dec;14(6):531-535. Epub 2020 Nov 7.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

The association between health benefits and physical activity has received increasing attention among researchers working on the prevention of noncommunicable disease. However, the number of studies on the association between daytime activities and visceral fat is limited. In this study, we evaluated how daily physical activity behaviors impact the visceral adipose tissue (VAT) and body mass index (BMI). A total of 3543 participants (1240 men, 2303 women) were included in this cross-sectional study. The duration of daily physical activities (sedentary time, standing time, and walking time) was classified into the six categories. Multiple regression analysis was carried out to compare continuous variables. VAT and BMI were used as dependent variables, and the daily physical activities were used as independent variables. All results were expressed after adjusting for confounders, including sex, age, Brinkman index, daily alcohol consumption, sleeping time, and medication for hypertension, dyslipidemia, and diabetes. The multiple regression analysis showed that sedentary time was significantly associated with VAT (beta = 1.145, p value = 0.002), whereas standing time was negatively associated with VAT (beta = -0.763, p value = 0.043). Walking time was negatively and robustly associated with all depending variables as follows: BMI (beta = -0.172, p value = 0.001) and VAT (beta = -2.023, p value <0.001). This study showed that a daily behavior time affects the accumulation of VAT and BMI. A shift from sedentary time to standing or walking time might be a key population approach to prevent cardiometabolic diseases.
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http://dx.doi.org/10.1016/j.orcp.2020.10.004DOI Listing
November 2020

Association between plasma levels of homocysteine, folate, and vitamin B, and dietary folate intake and hypertension in a cross-sectional study.

Sci Rep 2020 10 28;10(1):18499. Epub 2020 Oct 28.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B.
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http://dx.doi.org/10.1038/s41598-020-75267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595187PMC
October 2020

A multi-center, prospective study on the progression rate of asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on magnetic resonance imaging to idiopathic normal pressure hydrocephalus.

J Neurol Sci 2020 Dec 3;419:117166. Epub 2020 Oct 3.

Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III, Yamagata University School of Medicine, Yamagata, Japan. Electronic address:

Introduction: Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors.

Methods: We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as "asymptomatic ventriculomegaly with features of iNPH on MRI"; in the present study, asymptomatic was defined as "0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS)." We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values.

Results: In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

Conclusions: The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.
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http://dx.doi.org/10.1016/j.jns.2020.117166DOI Listing
December 2020

Daily Consumption of Coffee and Eating Bread at Breakfast Time Is Associated with Lower Visceral Adipose Tissue and with Lower Prevalence of Both Visceral Obesity and Metabolic Syndrome in Japanese Populations: A Cross-Sectional Study.

Nutrients 2020 Oct 11;12(10). Epub 2020 Oct 11.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

Background: The study aimed to investigate the association between daily consumption of coffee or green tea, with and without habitual bread consumption for breakfast, and components and prevalence of metabolic syndrome in Japanese populations.

Methods: The study population consisted of 3539 participants (1239 males and 2300 females). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analyses to evaluate the associations of daily coffee and green tea consumption with the prevalence of obesity, visceral obesity, and metabolic syndrome.

Results: Coffee consumption was associated with significantly lower proportions of visceral obesity (OR: 0.746, CI: 0.588-0.947) and metabolic syndrome (OR: 0.706, CI: 0.565-0.882). On the other hand, green tea was not associated with visceral obesity (OR: 1.105, CI: 0.885-1.380) or metabolic syndrome (OR: 0.980, CI: 0.796-1.206). The combination of daily drinking coffee and eating bread at breakfast time was associated with significantly lower proportions of obesity (OR: 0.613, CI: 0.500-0.751) ( = 0.911 for interaction), visceral obesity (OR: 0.549, CI: 0.425-0.710) ( = 0.991 for interaction), and metabolic syndrome (OR: 0.586, CI: 0.464-0.741) ( = 0.792 for interaction).

Conclusion: Coffee consumption was significantly associated with lower visceral adipose tissue and lower proportions of visceral obesity, but the same was not true for green tea consumption. Furthermore, in combination with coffee consumption, the addition of eating bread at breakfast time significantly lowered proportions of visceral obesity and metabolic syndrome, although there was no interaction between coffee and bread.
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http://dx.doi.org/10.3390/nu12103090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599629PMC
October 2020

Evaluation of myostatin as a possible regulator and marker of skeletal muscle-cortical bone interaction in adults.

J Bone Miner Metab 2020 Oct 12. Epub 2020 Oct 12.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Introduction: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions.

Methods: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups.

Results: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass.

Conclusions: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.
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http://dx.doi.org/10.1007/s00774-020-01160-8DOI Listing
October 2020

Growth of cortical bone thickness and trabecular bone density in Japanese children.

Bone 2020 12 3;141:115669. Epub 2020 Oct 3.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Background: The acquisition of a high bone density at a young age is a strategy to prevent fractures/falls later in life. We therefore decided to investigate the increases in cortical thickness (CoTh) and trabecular bone density (TBD) of children.

Methods: Subjects comprised 1314 students (678 boys and 636 girls) aged between 12 and 18 years. Lifestyle factors were examined with a self-administered questionnaire (sleep times, exercise habits, and calcium intake). Bone growth was assessed based on CoTh and TBD using an ultrasonic bone densitometer. Height, weight, and body fat percentage were also measured.

Results: Increases in CoTh and TBD occurred earlier in girls than in boys. Calcium intake was not sufficient at any of the ages examined, and sleep times were shorter than those recommended by the National Sleep Foundation. Increases in CoTh and TBD occurred subsequent to increases in height. Although increases in CoTh were observed with age in both sexes, TBD increased in boys until the age of 17 years and in girls until the age of 15 years. At 18 years of age, the young adult mean value was greater than 100% for CoTh but lower than 100% for TBD. A multivariate analysis identified age, body mass index (BMI), and exercise as independent positive factors for CoTh, while body fat percentage was an independent negative factor. Age and BMI were independent positive factors for TBD in both sexes, whereas body fat percentage was a positive factor in boys only.

Conclusions: The study found that CoTH and TBD varied with age and differed in increase in boys and girls; related factors of bone increase could also be found. The results of this study may contribute to the acquisition of high bone density in children and adolescents.
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http://dx.doi.org/10.1016/j.bone.2020.115669DOI Listing
December 2020

Midregional Proadrenomedullin Can Reflect the Accumulation of Visceral Adipose Tissue-A Key to Explaining the Obesity Paradox.

Int J Environ Res Public Health 2020 06 3;17(11). Epub 2020 Jun 3.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Background: The aim of this study was to investigate whether plasma midregional proadrenomedullin (MR-proADM) reflected body composition, such as body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), VAT/SAT ratio, body fat mass (BFM), and skeletal muscle mass (SMM).

Methods: A total of 2244 individuals (727 men and 1517 women) were included in the study. Multiple regression analysis was performed to assess the combined influence of variables: age, daily alcohol consumption, Brinkman index, sleeping time, metabolic equivalents, anamnesis for hypertension, dyslipidemia, diabetes, and body composition of MR-proADM, by using a stepwise forward selection method.

Results: MR-proADM was significantly related to all anthropometric indices (BMI, VAT, SAT, VAT/SAT ratio, BFM, and SMM) in men and women. On the basis of a stepwise forward selection method, VAT (men: beta = 0.184, < 0.001, women: beta = 0.203, < 0.001) and BFM (beta = 0.181, < 0.001) in women, were found to be significantly associated with MR-proADM.

Conclusion: This study suggests that plasma MR-proADM concentration is a more reliable indicator of VAT for fat distribution, and thus, MR-proADM may help better understand the obesity paradox. Changes in circulating levels of MR-proADM could possibly reflect changes in body composition, endocrine, and metabolic milieu.
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http://dx.doi.org/10.3390/ijerph17113968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312365PMC
June 2020

Sedentary Time is Associated with Cardiometabolic Diseases in A Large Japanese Population: A Cross-Sectional Study.

J Atheroscler Thromb 2020 Oct 8;27(10):1097-1107. Epub 2020 Apr 8.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine.

Aim: Accumulating evidence reveals that sedentary behavior is associated with mortality and cardiometabolic disease; however, there are potential age and sex differences in sedentary behavior and health outcomes that have not been adequately addressed. This study aimed to determine the association of sedentary behavior with cardiometabolic diseases such as hypertension, dyslipidemia, diabetes mellitus, and its risk factors in a large Japanese population according to age and sex.

Methods: Using data from the Japan Multi-Institutional Collaborative Cohort Study obtained from baseline surveys, data of 62,754 participants (27,930 males, 34,824 females) were analyzed. This study uses a cross-sectional design and self-administered questionnaires to evaluate sedentary time and anamnesis. For the logistic regression analysis, sedentary time <5 h/day was used as the reference and then adjusted for age, research areas, leisure-time metabolic equivalents, and alcohol and smoking status. From the analysis of anthropometric and blood examinations, 35,973 participants (17,109 males, 18,864 females) were analyzed.

Results: For hypertension and diabetes, sedentary time was associated with a significantly higher proportion of male participants. Both sexes were associated with a significantly higher proportion of participants with dyslipidemia. Participants who had longer sedentary time tended to have increased levels of blood pressure, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C), and decreased levels of HDL-C, especially in the 60-69 years group.

Conclusions: Independent of leisure-time physical activity, sedentary time was associated with cardiometabolic diseases in a large Japanese population classified by age and sex. Our findings indicate that regularly interrupting and replacing sedentary time may contribute to better physical health-related quality of life.
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http://dx.doi.org/10.5551/jat.54320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585914PMC
October 2020

Subtype-specific gout susceptibility loci and enrichment of selection pressure on and identified by subtype genome-wide meta-analyses of clinically defined gout patients.

Ann Rheum Dis 2020 05 1;79(5):657-665. Epub 2020 Apr 1.

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan

Objectives: Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years.

Methods: Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype.

Results: In addition to the eight loci we reported previously, two novel loci, and , were identified at a genome-wide significance level (p<5.0×10) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, and , from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on in addition to loci for all subtypes except for normal type gout.

Conclusions: Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.
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http://dx.doi.org/10.1136/annrheumdis-2019-216644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213308PMC
May 2020

Differential Effect of Polymorphisms on Body Mass Index Across the Life Course of Japanese: The Japan Multi-Institutional Collaborative Cohort Study.

J Epidemiol 2021 Mar 7;31(3):172-179. Epub 2020 Mar 7.

Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine.

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities.

Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models.

Results: We found a significant association (P < 0.05/282 = 1.77 × 10) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake.

Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.
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http://dx.doi.org/10.2188/jea.JE20190296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878711PMC
March 2021

Sensitive and selective quantification of mid-regional proadrenomedullin in human plasma using ultra-performance liquid chromatography coupled with tandem mass spectrometry.

J Pharm Biomed Anal 2020 May 11;183:113168. Epub 2020 Feb 11.

Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.

Mid-regional pro-adrenomedullin (MR-proADM) is suggested to be a prognostic indicator for various diseases. Plasma MR-proADM concentration is commonly measured using immunoassays based on its immunochemical characteristics. However, some immunological interactions affect the measured concentration. We developed and validated a sensitive and selective method for measuring plasma MR-proADM concentration using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and evaluated its clinical applicability. Plasma samples were prepared by protein precipitation and solid-phase extraction. Samples obtained from healthy volunteers (n = 38), patients with chronic kidney disease (CKD) stages 3 and 4-5 (non-dialysis; n = 20 and 17, respectively), and CKD stage 5D (dialysis; n = 34) were analyzed. Within-batch and batch-to-batch accuracy of the UPLC-MS/MS assay for quality control samples ranged from -0.69 % to 8.05 % and from 1.72 % to 5.76 %, respectively. The lower limit of quantification was 0.4 ng mL. The MR-proADM concentration determined using the UPLC-MS/MS assay correlated strongly with that determined using the immunoassay (Pearson's product-moment correlation coefficient [r] = 0.7875, p < 0.001). Median (range) plasma MR-proADM concentrations of healthy volunteers, patients with CKD stages 3 and 4-5, and patients with CKD stage 5D were 0.67 (0.43-1.27), 1.89 (0.65-6.68), 3.86 (1.60-8.75) and 3.97 (0.66-9.20) ng mL, respectively, and a significant difference among four groups was confirmed. We established a sensitive and selective method for determining plasma MR-proADM concentration using UPLC-MS/MS. Our novel UPLC-MS/MS assay for determining plasma MR-proADM concentration can be used in the clinical setting and may have better selectivity than the immunoassay method.
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http://dx.doi.org/10.1016/j.jpba.2020.113168DOI Listing
May 2020

Validity of stress assessment using heart-rate variability in newborns.

Pediatr Int 2020 Jun 8;62(6):694-700. Epub 2020 Jun 8.

Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level.

Methods: We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined.

Results: The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time.

Conclusions: The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.
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http://dx.doi.org/10.1111/ped.14149DOI Listing
June 2020

Association between Helicobacter pylori infection and dental pulp reservoirs in Japanese adults.

BMC Oral Health 2019 12 2;19(1):267. Epub 2019 Dec 2.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Background: Helicobacter pylori (H. pylori) colonize the stomach and are considered an etiological agent of gastric cancer. The oral cavity is a transmission route to the stomach, but the exact site of colonization has not yet been explicated. Our study investigated the association between H. pylori infection and presence in oral samples.

Methods: Dental pulp, supragingival plaque, and saliva from 192 patients visiting the Dentistry's outpatient clinic were collected for testing. The H. pylori ureA gene was identified via Nested PCR. Urine anti-H. pylori antibody test was utilized to detect infection.

Results: Twenty-five subjects were found to be antibody-positive. PCR analysis of dental pulp revealed that 23 subjects possessed the ureA gene. Twenty-one subjects were positive for both antibodies and genes in dental pulp. PCR testing revealed that 2 subjects were positive in dental plaque but negative for saliva. The subjects positive for H. pylori in dental pulp expressed clinical signs of severe dental caries.

Conclusions: H. pylori infected subjects expressed H. pylori in samples from the oral cavity. The main reservoir for infection within the oral cavity was determined to be dental pulp. Moreover, H. pylori are likely transmitted from dental caries to the root canal.
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http://dx.doi.org/10.1186/s12903-019-0967-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889519PMC
December 2019

The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population.

J Lipid Res 2020 01 6;61(1):86-94. Epub 2019 Nov 6.

Departments of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.
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http://dx.doi.org/10.1194/jlr.P091546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939595PMC
January 2020

Development of malignancies and changes in time-dependent hemoglobin A1c among a nondiabetic population: longitudinal analysis.

Acta Diabetol 2020 Feb 9;57(2):189-196. Epub 2019 Aug 9.

Ohta Nishinouchi Hospital, Koriyama, Japan.

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.
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http://dx.doi.org/10.1007/s00592-019-01396-5DOI Listing
February 2020

Inverse association of plasma leptin with cortical thickness at distal radius determined with a quantitative ultrasound device in patients with type 2 diabetes mellitus.

J Diabetes Investig 2020 Jan 5;11(1):174-183. Epub 2019 Jun 5.

Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

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 (β = -0.258, P < 0.001), but not trabecular BMD. Furthermore, plasma leptin level retained a significant association with CoTh after further adjustment for BMI (β = -0.237, P < 0.001) and BMI plus waist-to-hip ratio (β = -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.
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http://dx.doi.org/10.1111/jdi.13071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944815PMC
January 2020

Assessment of anthropometric indices other than BMI to evaluate arterial stiffness.

Hypertens Res 2019 10 24;42(10):1599-1605. Epub 2019 Apr 24.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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 (β = 0.087, p = 0.002), visceral adipose tissue (VAT; β = 0.081, p = 0.002), and the visceral/subcutaneous adipose tissue (VAT/SAT) ratio (β = 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 (β = 0.103, p = 0.038), BRI (β = 0.104, p = 0.036), VAT (β = 0.167, p = 0.001), and the VAT/SAT ratio (β = 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.
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http://dx.doi.org/10.1038/s41440-019-0264-0DOI Listing
October 2019

Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use prior to medical intensive care unit admission and in-hospital mortality: propensity score-matched cohort study.

J Nephrol 2019 Aug 1;32(4):595-603. Epub 2019 Apr 1.

Division of Nephrology, Department of Medicine, St. Luke's International Hospital, Tokyo, Japan.

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.
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http://dx.doi.org/10.1007/s40620-019-00603-4DOI Listing
August 2019

Background Risk Factors Associated with Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus: A Nationwide Hospital-Based Survey in Japan.

J Alzheimers Dis 2019 ;68(2):735-744

Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

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.
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http://dx.doi.org/10.3233/JAD-180955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484254PMC
July 2020

Alcohol consumption behaviours in the immediate aftermath of earthquakes: time series study.

BMJ Open 2019 03 7;9(3):e026268. Epub 2019 Mar 7.

Society, Human Development and Health, Harvard School of Public Health, Boston, Massachusetts, USA.

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 (β 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.
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http://dx.doi.org/10.1136/bmjopen-2018-026268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429926PMC
March 2019

Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population.

Sleep 2019 06;42(6)

Department of Public Health, Nagoya City University Graduate School of Medicine, Nagoya, Japan.

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.
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http://dx.doi.org/10.1093/sleep/zsz046DOI Listing
June 2019

Malignancy incidences by glycemic control among diabetic patients.

Endocr Connect 2018 Dec;7(12):1457-1463

Department of Endocrinology St. Luke's International Hospital, Tokyo, Japan.

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 five 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, 2729 participants were included in this study, where the mean age was 62.6 (standard deviation (s.d.): 7.8) and 2031 (74.4%) were male. The mean disease duration of diabetes was 7.6 (s.d.: 7.6) years, and 1688 (61.8%) were prescribed medications. Median follow-up was 1443.5 (interquartile range (IQR): 2508) 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%); OR 1.07, 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.
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http://dx.doi.org/10.1530/EC-18-0355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300859PMC
December 2018