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Introduction: Lumbar spinal stenosis (LSS) is a lumbar spinal disorder that causes leg symptoms and intermittent claudication. It is reported that the risk factors for low back pain include age, family history, smoking, obesity, work-related physical load, exercise, and depression. This was a multicenter, cross-sectional survey, and the aim of this study was to investigate the prevalence of LSS by age and the relationships between LSS and psychosocial factors and job satisfaction.Methods: This study enrolled subjects aged 50 years and over from a survey of LSS in 2177 hospitals and general practices nationwide. The clinical characteristics of the LSS and non-LSS groups were compared using the χ2 test, and the multivariate logistic regression analysis was performed to examine associations between exercise, perceived stress, strenuous use of the low back or legs, job satisfaction, and LSS.Results: In total, 18,642 patients (8338 males, 10,267 females) were analyzed. The rate of LSS was 38.3% and it increased with age. Regular exercise was less common among those in the LSS group than those in the non-LSS group (p<0.001). Satisfaction in all job-related items was less in the LSS group than in the non-LSS group (p<0.001). The odds for having LSS were higher in subjects having perceived stress and strenuous use of the low back or legs (p=0.001). The odds ratios of heart diseases and hypertension (p<0.001) were higher in the LSS group.Conclusion: This study investigated factors associated with LSS. The prevalence of LSS increased with age. Perceived stress and strenuous use of the low back or legs might be associated with LSS, and job satisfaction was lower with LSS. [ABSTRACT FROM AUTHOR]

The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. Level 3. [ABSTRACT FROM AUTHOR]

Aim: To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods: A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results: During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion: Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml. [ABSTRACT FROM AUTHOR]

A methodology for modeling covariate effects on the time-to-event data is developed. The covariates are allowed to be time dependent and their effects are modeled using polynomial splines in order to account for possibly non-linear effects. The methodology is applied to examine the effects on the incidence brain infarction based on a cohort study in Hisayama, Japan. The results indicate that at least two non-linear effects are significant (body mass index and systolic blood pressure) and there is a time-varying drug effect. The resulting significant risk factors are assessed by the proposed method that is more flexible and hence less biased than the traditional procedures where linear effects are imposed. These results are extremely important to the local medical investigation. In particular, more insight has been gained by examining the non-linear effects. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The reference values of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in patients with lumbar spinal stenosis (LSS) are still unknown. This multicenter cross-sectional survey was performed to determine the reference values and disease-specific characteristics of deterioration of QOL caused by LSS itself, not by aging, through comparison of patients with and without LSS who had an outpatient visit for low back pain by age and sex groups.Methods: The present study was performed at 564 medical centers and clinics. The JOABPEQ was measured for 8338 patients aged 20 years or over who came to an outpatient clinic for low back pain (LBP) and were examined for whether they had LSS using the LSS diagnosis support tool (LSS-DST). Scores in the five JOABPEQ domains were compared between the LSS group and the LBP without LSS group (LBP group) for each age and sex group.Results: Scores for Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders were significantly lower in the LSS group than in the LBP group.Conclusion: The percentiles of JOABPEQ scores in patients with LSS were clarified and could be used as reference values. Deterioration of QOL caused by LSS itself, not by aging, are characterized by Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders. [ABSTRACT FROM AUTHOR]

Background The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was developed in 2007, including the five domains of Pain-related disorder, Lumbar spine dysfunction, Gait disturbance, Social life disturbance, and Psychological disorder. It is used by physicians to evaluate treatment efficacy by comparing scores before and after treatment. However, the JOABPEQ does not allow evaluation of the severity of a patient's condition compared to the general population at a single time point. Given the unavailability of a standard measurement of back pain, we sought to establish reference scores and interquartile ranges using data obtained from a multicenter, cross-sectional survey taken in Japanese primary care settings. Methods The Lumbar Spinal Stenosis Diagnosis Support Tool project was conducted from 2011 to 2012 in 1657 hospitals in Japan to investigate the establishment of reference scores using JOABPEQ. Patients aged ≥ 20 years undergoing medical examinations by either non-orthopaedic primary care physicians or general orthopedists were considered for enrollment. Results A total of 10,651 consecutive low back pain patients (5331 men, 5320 women, 18 subjects with missing sex data) who had undergone a medical examination were included. Reference scores and interquartile ranges for each of the five domains of the JOABPEQ according to age and sex were recorded. The median score and interquartile range are the same in the domain of Pain-related disorder in all ages and sexes. The reference scores for Gait disturbance, Social life disturbance and Psychological disorder declined with increasing age in both age- and sex-stratified groups, while there was some different trend in Lumbar spine dysfunction between men and women. Conclusion Reference scores and interquartile ranges for JOABPEQ were generated based on the data from the examination data. These provide a measurement standard to assess patient perceptions of low back pain at any time point during evaluation or therapy. [ABSTRACT FROM AUTHOR]

Background: Numbness in the soles of both feet at rest or bowel/bladder dysfunction can occur in patients with lumbar spinal stenosis (LSS), especially in patients with cauda equina lesions. The purpose of this study was to clarify the relationship between cauda equina symptoms at rest and quality of life (QOL) in LSS patients using standardized questionnaires developed for the Japanese population.Methods: A survey was conducted in 564 hospitals and general practice clinics nationwide from December 1, 2011 to December 31, 2012. All patients who visited hospital or clinic because of low back pain were included. Patients were diagnosed with LSS using the LSS-Diagnostic Support Tool (LSS-DST), and the severity of the disease was measured using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) for quality of life. Presence of both sole numbness and/or bowel/bladder dysfunction were determined by medical interview. 3647 patients were diagnosed with LSS according to the results of the LSS-DST. 1294 of these patients (35.5%) had symptoms at rest. Of these patients, 359 patients with sole numbness, 135 patients with bowel/bladder dysfunction, and 52 patients with both numbness and bowel/bladder dysfunction were compared to the patients without rest symptoms (n = 2182). Comparisons between groups with or without sole numbness and bowel/bladder dysfunction were performed using statistical analysis of JOABPEQ responses in the categories of pain-related disorder, lumbar spine disorder, gait disturbance, social life disturbance, and psychological disorder.Results: All groups with sole numbness and/or bowel/bladder dysfunction had statistically lower (worse) scores in all categories of the JOABPEQ compared to the group without these symptoms at rest.Conclusion: LSS patients having numbness in the soles of both feet at rest or bowel/bladder dysfunction had lower measurements of QOL and activities of daily living than those patients without symptoms at rest. These symptoms appear to be related to QOL of LSS patients. [ABSTRACT FROM AUTHOR]

Aim This retrospective cohort study evaluated the effectiveness of injury to the endometrium prior to the frozen-thawed embryo transfer (FET) cycle in patients with repeated implantation failure (RIF) in our clinic. Methods Included in this study were 173 patients, aged ≤ 41 years, who failed to become pregnant after repeating fair and/or good embryo transfer more than twice between February 2012 and February 2015. The patients were divided into three groups: Group A ( n = 38) underwent soft curettage to the endometrium twice, prior to the FET cycle; Group B ( n = 45) underwent hysteroscopy prior to the FET cycle, with no significant factors, such as endometrial polyp; and Group C ( n = 90) was the no-treatment group. Results The clinical pregnancy rate per transfer was found to be statistically significant between Group A at 42.1% (16/38) and Group C at 22.2% (20/90). The crude and adjusted odds ratios (OR) were 2.55 and 2.49 (95% confidence intervals 1.13-5.78, P = 0.03 and 1.01-6.17, P = 0.048) respectively. Group B with only hysteroscopy had a higher pregnancy rate of 35.6% (16/45) than Group C, but showed no statistical significance ( P = 0.103). Conclusion These results suggest that injuring the endometrium has a positive effect on pregnancy. [ABSTRACT FROM AUTHOR]

Background: Diagnostic support tools for lumbar spinal stenosis such as the Self-administered, Self-reported History Questionnaire have been developed in Japan, but no report has demonstrated the diagnostic accuracy of this questionnaire in Japanese primary care settings. This multicenter, cross-sectional survey was performed to evaluate and improve the diagnostic accuracy of this questionnaire for lumbar spinal stenosis patients in Japanese primary care settings.Methods: The lumbar spinal stenosis diagnosis support tool project was conducted in 1657 hospitals to evaluate the diagnostic accuracy of the Self-administered, Self-reported History Questionnaire in Japan from 2011 to 2012. Consecutive adults (≥50 years old) from physicians, including non-orthopedic general practitioners and orthopedic general practitioners, were considered for enrollment. Consecutive adults (≥50 years old) with low back pain from hospital-based orthopedic surgeons were also considered for enrollment. The diagnostic accuracy of the Self-administered, Self-reported History Questionnaire with initial and several new cutoff points in classifying patients according to the presence of lumbar spinal stenosis was assessed in terms of sensitivity, specificity and negative predictive values.Results: Among the 33,545 patients, 10,199 (30.4 %) were diagnosed with lumbar spinal stenosis by the physicians. The Self-administered, Self-reported History Questionnaire version 1.1 with a new cutoff point was more sensitive than the Self-administered, Self-reported History Questionnaire version 1.0 with the initial cutoff point (79.8 vs. 68.3 %) and less specific (68.8 vs. 75.1 %) for lumbar spinal stenosis diagnosis. The respective negative predictive values were 88.5 and 84.3 %.Conclusions: The Self-administered, Self-reported History Questionnaire version 1.1 with the new cutoff was more sensitive and had higher negative predictive value than version 1.0 with the initial cutoff. Therefore, the improved Self-administered, Self-reported History Questionnaire version 1.1 can be used for lumbar spinal stenosis screening, and its use may improve the quality of lumbar spinal stenosis diagnostic practice in Japanese primary care settings. [ABSTRACT FROM AUTHOR]

We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007–2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death. [ABSTRACT FROM AUTHOR]

Despite the applicability of the lumbar spinal stenosis (LSS)-diagnosis support tool (DST) and the LSS-self-administered, self-reported history questionnaire (SSHQ), their diagnostic accuracy has never been compared with that of the well-known North American Spine Society (NASS) clinical description of LSS. This study aimed to compare the diagnostic accuracy of the two diagnostic tools with that of the NASS guidelines' clinical description of LSS in a Japanese secondary care hospital setting. This multicenter cross-sectional study used data from the lumbar spinal stenosis diagnostic support tool (DISTO) project, which was conducted from December 1, 2011 to December 31, 2012. Japanese adults with low back pain (LBP) aged ≥20 years were consecutively included. The reference standard was LSS diagnosed by orthopedic physicians. The diagnostic accuracy of the two support tools was compared. Of 3,331 patients, 1,416 (42.5%) patients were diagnosed with LSS. The NASS clinical description of LSS had a sensitivity of 63.9% and specificity of 89.5%. The LSS-DST and LSS-SSHQ had sensitivities of 91.3% and 83.8% and specificities of 76.0% and 57.6%, respectively, with substantial improvements in sensitivity (P < 0.0001). Similar results were obtained when we limited included patients to those aged >60 years. These findings indicated that the LSS-DST and LSS-SSHQ were more sensitive in screening patients with LBP for a diagnosis of LSS than the NASS clinical description of LSS. This study strongly supports prioritizing the use of either of these two diagnostic support tools for screening. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal stenosis (LSS) is a major clinical problem associated with back pain, intermittent claudication, leg pain, and leg numbness. Diagnostic support tools for LSS such as the self-administered, self-reported history questionnaire (SSHQ) and developmental clinical diagnosis support tool (ST) have been validated in Japan. However, the degree of awareness and use of these two diagnostic support tools for LSS in Japan has not been clarified. The aims of the current study were to determine the degree of awareness and use of these two diagnostic support tools by Japanese physicians. Furthermore, we compared these results among nonorthopedic general practitioner (GP), orthopedic GP, and hospital-based orthopedic physicians. Methods: The LSS Diagnosis Support Tool (DISTO) Project was conducted to evaluate the degree of awareness and use of these two diagnostic support tools in Japan from 2011 to 2012. A total of 1,811 answers were obtained from physicians including nonorthopedic general practitioners (GP), orthopedic GPs, and hospital-based orthopedic physicians. Questions were (1) Do you know about these two diagnostic tools? and (2) If you know about these two diagnostic tools, have you used them? Results: The degree of awareness of ST and SSHQ was about 30 and 26 % by nonorthopedic GPs, 70 and 46 % by orthopedic GPs, and 68 and 41 % by hospital-based orthopedic physicians. The degree of awareness of ST and SSHQ by nonorthopedic GPs was significantly lower than by orthopedic GPs or hospital-based orthopedic physicians ( p < 0.001). For physicians who were aware of ST and SSHQ, the degree of use of ST or SSHQ was <50 % by nonorthopedic GPs, orthopedic GPs, and hospital-based orthopedic physicians. Conclusions: We expect that use of the ST or SSHQ tools in primary care will improve the accuracy of diagnosis and lead to improved quality of patient care. The low proportion of awareness by nonorthopedic GPs (<30 %) and use by all physicians (<50 %) indicate a need to encourage physicians to use ST and SSHQ more frequently. [ABSTRACT FROM AUTHOR]

Background. Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. Subjects and methods. We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. Results. During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). Conclusions. This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease. [ABSTRACT FROM AUTHOR]

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0–41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8–100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers. [ABSTRACT FROM AUTHOR]

Background: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was developed in 2007, including the five domains of Pain-related disorder, Lumbar spine dysfunction, Gait disturbance, Social life disturbance, and Psychological disorder. It is used by physicians to evaluate treatment efficacy by comparing scores before and after treatment. However, the JOABPEQ does not allow evaluation of the severity of a patient's condition compared to the general population at a single time point. Given the unavailability of a standard measurement of back pain, we sought to establish reference scores and interquartile ranges using data obtained from a multicenter, cross-sectional survey taken in Japanese primary care settings.Methods: The Lumbar Spinal Stenosis Diagnosis Support Tool project was conducted from 2011 to 2012 in 1657 hospitals in Japan to investigate the establishment of reference scores using JOABPEQ. Patients aged ≥ 20 years undergoing medical examinations by either non-orthopaedic primary care physicians or general orthopedists were considered for enrollment.Results: A total of 10,651 consecutive low back pain patients (5331 men, 5320 women, 18 subjects with missing sex data) who had undergone a medical examination were included. Reference scores and interquartile ranges for each of the five domains of the JOABPEQ according to age and sex were recorded. The median score and interquartile range are the same in the domain of Pain-related disorder in all ages and sexes. The reference scores for Gait disturbance, Social life disturbance and Psychological disorder declined with increasing age in both age- and sex-stratified groups, while there was some different trend in Lumbar spine dysfunction between men and women.Conclusion: Reference scores and interquartile ranges for JOABPEQ were generated based on the data from the examination data. These provide a measurement standard to assess patient perceptions of low back pain at any time point during evaluation or therapy. [ABSTRACT FROM AUTHOR]

Background: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese.Methods: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort.Results: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort.Conclusions: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual’s risk of future gastric cancer. [ABSTRACT FROM AUTHOR]

Aim: The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan. Methods: Two hundred and fifty‐six patients diagnosed with AIH were enrolled. A person‐year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from “The Monitoring of Cancer Incidence in Japan Project” in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined. Results: Twenty‐seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34–2.96), and was high among female patients at 2.49 (95% CI, 1.60–3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05–25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45–40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64–52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485). Conclusion: The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up. [ABSTRACT FROM AUTHOR]

Background: A nationwide survey of autoimmune hepatitis (AIH) patients was performed in Japan in 2015. The aims of this study were to elucidate the trends and characteristics of AIH in Japan, in addition to identifying differences in AIH between acute hepatitis and chronic hepatitis.Methods: Questionnaires about patients with AIH diagnosed from 2009 to 2013 were sent to 437 hospitals or clinics with hepatology specialists.Results: A total of 1682 patients were enrolled. The mean age at diagnosis was 60.0 years, and 87.1 % of patients were female. Serum immunoglobulin G levels were high, peaking at 1.5-2.0 g/dL. Histological diagnoses of chronic hepatitis, acute hepatitis, and cirrhosis were seen in 79.6, 11.7, and 6.7 % of patients respectively. In addition to elevation of aminotransferase levels, the frequencies of emperipolesis and human leukocyte antigen (HLA)-DR2 positivity were higher in patients with acute hepatitis than in those with chronic hepatitis. Approximately 80 % of patients were treated with corticosteroids, and in 97.7 % of them, their condition improved. Steroid pulse therapy was more frequently given to patients with acute hepatitis than to those with chronic hepatitis.Conclusions: In the present nationwide survey of AIH patients in Japan, patients with acute hepatitis had clinical features different from those of patients with chronic hepatitis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome.Methods: We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome.Results: During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts.Conclusions: Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered. [ABSTRACT FROM AUTHOR]

Aims/Introduction The usefulness of markers of carotid plaque, such as sum ( PS) and maximum (P-max) of the plaque thickness, in combination with intima-media thickness in the common carotid artery ( CIMT) for the detection of obstructive coronary artery disease ( CAD) was investigated in patients with type 2 diabetes without known CAD. Materials and Methods B-mode ultrasonographic scanning of the carotid artery and multislice computed tomography coronary angiography were carried out in 332 asymptomatic patients with type 2 diabetes. Results For the presence of obstructive CAD when incorporating PS or P-max to standard risk factors in a multiple logistic regression model, the classification ability in PS and P-max increased greatly (area under the curve [ AUC] 0.827 vs 0.720 [net reclassification index { NRI} = 0.652, P < 0.01] and AUC 0.820 vs 0.720 [ NRI = 0.775, P < 0.01], respectively), and it in CIMT increased slightly ( AUC 0.740 vs 0.720, NRI = 0.230, P = 0.041). Furthermore, the classification abilities for a model with interaction terms between PS* or P-max* and CIMT were statistically larger than those for a model without interaction terms ( AUC 0.833 vs 0.827 [ NRI = 0.411, P < 0.01] and 0.823 vs 0.820 [ NRI = 0.269, P < 0.05], respectively). Partitioning showed the patients in the values of the PS <2.6 mm and CIMT <0.725 mm (100%), or in P-max <2.1 mm and CIMT <0.725 mm (95.4%), did not have obstructive CAD, whereas those in the values of PS [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a significant health problem worldwide, with a prevalence in the general population of approximately 40%. Alexithymia — the personality trait of having difficulties with emotional awareness and self-regulation — has been reported to contribute to an increased risk of several chronic diseases and health conditions, and limited research indicates a potential role for alexithymia in the development and maintenance of chronic pain. However, no study has yet examined the associations between alexithymia and chronic pain in the general population. Methods: We administered measures assessing alexithymia, pain, disability, anxiety, depression, and life satisfaction to 927 adults in Hisayama, Japan. We classified the participants into four groups (low-normal alexithymia, middle-normal alexithymia, high-normal alexithymia, and alexithymic) based on their responses to the alexithymia measure. We calculated the risk estimates for the criterion measures by a logistic regression analysis. Results: Controlling for demographic variables, the odds ratio (OR) for having chronic pain was significantly higher in the high-normal (OR: 1.49, 95% CI: 1.07–2.09) and alexithymic groups (OR: 2.56, 95% CI: 1.47–4.45) compared to the low-normal group. Approximately 40% of the participants belonged to these two high-risk groups. In the subanalyses of the 439 participants with chronic pain, the levels of pain intensity, disability, depression, and anxiety were significantly increased and the degree of life satisfaction was decreased with elevating alexithymia categories. Conclusions: The findings demonstrate that, in the general population, higher levels of alexithymia are associated with a higher risk of having chronic pain. The early identification and treatment of alexithymia and negative affect may be beneficial in preventing chronic pain and reducing the clinical and economic burdens of chronic pain. Further research is needed to determine if this association is due to a causal effect of alexithymia on the prevalence and severity of chronic pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged >=40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors. [ABSTRACT FROM AUTHOR]

The authors examined the association between white blood cell (WBC) count and the development of gastric cancer in a 19-year follow-up study of 2,558 Japanese subjects aged ≥40 years (1988–2007). The subjects were stratified into 4 groups according to baseline WBC quartile (≤4.4, 4.5–5.2, 5.3–6.3, or ≥6.4 × 103 cells/μL). During follow-up, 128 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer increased linearly with higher WBC level: 1.7, 2.6, 3.9, and 5.4 per 1,000 person-years, respectively, for the 4 quartile groups (P for trend < 0.01). The risk of gastric cancer was 2.22-fold (95% confidence interval: 1.19, 4.14) higher in the highest WBC quartile group than in the lowest group after adjustment for confounding factors. With respect to Helicobacter pylori infection status, H. pylori-seropositive subjects in the highest WBC quartile group showed a significantly greater risk of gastric cancer than those in the lower 3 quartile groups, whereas such an association was not observed in H. pylori-seronegative subjects. There was no evidence of heterogeneity in the association (P for heterogeneity = 0.65). The study findings suggest that higher WBC levels are a risk factor for gastric cancer, especially in subjects with H. pylori infection. [ABSTRACT FROM PUBLISHER]

Background and Aim: Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4-related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients. Methods: Serum IgG4 was measured in 35 type 1 AIP patients and 71 non-AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients. Results: Serum IgG4 in type 1 AIP was significantly higher than in non-AIP ( P < 0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P < 0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut-off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver-operator characteristic curve data. Conclusions: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4-related disease with type 1 AIP. [ABSTRACT FROM AUTHOR]

Background: The present study was performed to compare the effects of pars plana vitrectomy (PPV) and single intravitreaous triamcinolone acetonide (IVTA) on diabetic macular edema (DME) in paired eyes. Methods: Prospective comparative study on randomized paired-eyes was carried out at two hospitals. Forty eyes of 20 patients with bilateral DME were included. One randomly-selected eye was treated with PPV (PPV group), and the other eye was treated with IVTA (4 mg, IVTA group). The central macular thickness (CMT) measured by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) were monitored for 12 months after treatment. Changes from baseline and differences between groups were analyzed using a mixed model. Results: At 1 and 3 months, CMT decreased significantly in the IVTA group compared to baseline ( p < 0.0001 both), but CMT then increased gradually and no significant difference was found at 12 months ( p = 0.90). In the PPV group, CMT decreased continuously and reached a significant level at 12 months ( p < 0.0001). CMT of the IVTA group was significantly less than that of the PPV group at 1 month ( p = 0.009); however, there was no significant difference at 3 months. Conversely, CMT was significantly less in the PPV group than in the IVTA group at 12 months ( p = 0.0003). The changes of BCVA paralleled those of CMT, but no significant difference was detected between baseline BCVA and any time point. Conclusions: Despite the short-term improvement, DME recurred 6 months after IVTA, while it remained resolved after PPV. Although this study did not reveal a significant change of BCVA with either treatment, PPV resolved DME more effectively than IVTA at 1 year. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between serum total bilirubin levels and diabetic retinopathy prevalence in participants of the Hisayama Study who had diabetes and impaired glucose metabolism. Design: Population-based, cross-sectional study. Participants: Of 3119 participants of the Hisayama Study Eye Examinations in 2007, Japan, 1672 aged ≥40 years with either diabetes or impaired glucose metabolism (defined by a 75-g oral glucose tolerance test) were enrolled in the present study. Methods: Diabetic retinopathy was assessed via ophthalmic examination after pupil dilatation. The presence and the severity of diabetic retinopathy were determined by grading of color fundus photographs using the modified Airlie House classification system. Association of diabetic retinopathy with serum bilirubin quartiles was assessed using logistic regression model adjusting for age and known risk factors for diabetic retinopathy. Main Outcome Measures: Prevalent diabetic retinopathy. Results: Diabetic retinopathy was present in 70 of 1672 (4.2%) participants. The prevalence of diabetic retinopathy in persons with the highest bilirubin quartile (≥0.9 mg/dL) was 2.7%, compared with the prevalence of 3.4%, 5.1%, and 5.1% in those with the first (<0.6 mg/dL), second (0.6–0.69 mg/dL), and third quartiles (0.7–0.89 mg/dL). After adjusting for factors known to be associated with diabetic retinopathy, the prevalence was significantly lower among persons with the highest bilirubin quartile compared with those with the lowest quartile (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.09–0.72) or compared with those in the 3 lower quartiles (OR, 0.25; 95% CI, 0.11–0.58). Conclusions: Elevated serum bilirubin levels may be protective against diabetic retinopathy among persons with either diabetes or impaired glucose metabolism, independent of known risk factors for diabetic retinopathy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Besides n-octanoyl ghrelin (O-ghrelin), there is another acyl-form of ghrelin; n-decanoyl ghrelin (D-ghrelin), which has a decanoic acid modification. In this study, we examined the kinetics of D-ghrelin immunoreactivity in human plasma in comparison to O-ghrelin or total ghrelin by using a D-ghrelin-specific radioimmunoassay. The dynamics of plasma D-ghrelin was assessed following glucose- or meal-ingestion in healthy, non-obese subjects (5 males and 5 females). Correlations were also analyzed between the levels of plasma D-ghrelin and anthropometric or metabolic indicators in healthy human subjects (n=111, BMI 17.4–34.3). The plasma levels of D-ghrelin, like O- or T-ghrelin, significantly declined (p <0.05 for male and p <0.01 for female) 60min after the ingestion of glucose in non-obese subjects. However, in the same subjects, no significant decline was noted in the levels of D-ghrelin, unlike O- or T-ghrelin, upon the meal ingestion. A significant increase was observed in the proportion of plasma D-ghrelin levels to that of T-ghrelin (p <0.05) in the healthy human subjects as BMI increased, unlike the proportion of O-ghrelin to T-ghrelin, which did not change. Since D-ghrelin possesses almost the same potential as that of O-ghrelin with regard to the feeding-stimulation, these differences between the dynamics of D- and O-ghrelin in human plasma might influence appetite-control, especially in those with increased BMI. [Copyright &y& Elsevier]

Background. The purpose of this study is to investigate the relationship between serum resistin levels and chronic kidney disease (CKD).Methods. A total of 3192 community-dwelling subjects (1377 men, 1815 women), aged ≥40 years and without renal failure, were divided into four groups according to quartiles of serum resistin concentrations: ≤7.1, 7.2–9.9, 10.0–14.7 and ≥14.8 ng/mL. The associations of resistin levels with renal function status were examined cross-sectionally. The estimated glomerular filtration rate (eGFR) was calculated using the equation from the Modification of Diet in Renal Disease Study, and CKD was defined as an eGFR of <60 mL/min/1.73 m2.Results. The age- and sex-adjusted mean values of eGFR decreased significantly with elevating quartiles of resistin (P for trend <0.001). The age- and sex-adjusted odds ratios (ORs) for the presence of CKD increased progressively with higher quartiles of resistin. This trend remained robust even after controlling for age, sex, body mass index, diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), triglycerides, high-density lipoprotein and total cholesterol, hypertension, current smoking, current drinking, and regular exercise [second quartile: OR 1.44, 95% confidence interval (CI) 1.05–1.99; third quartile: OR 2.15, 95% CI 1.58–2.92; fourth quartile: OR 2.32, 95% CI 1.71–3.16; P for trend <0.001]. In stratified analyses, high resistin level (≥7.2 ng/mL) was a significant relevant factor in CKD, independent of HOMA-IR or hs-CRP level.Conclusion. Our findings suggest that elevated resistin level is significantly associated with the likelihood of CKD in the general Japanese population. [ABSTRACT FROM AUTHOR]

Background. Chronic kidney disease (CKD) is increasingly recognized as a leading public health issue. However, there are limited data assessing secular trends in the prevalence of CKD in general Asian communities. [ABSTRACT FROM PUBLISHER]

Recent genome-wide association study using four prospective population-based cohorts identified two single-nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579, to be significantly associated with the incidence of atherothrombotic stroke. To examine the association of these SNPs with atherothrombotic stroke in the Japanese population, we carried out a case–control association study using a total of 3784 cases and 3102 controls. We also examined the effect of these SNPs on the subtypes of ischemic stroke. Association analysis was carried out using logistic regression model after adjustment of age, sex and cardiovascular risk factors. Rs12425791 was significantly associated with atherothrombotic stroke (P=0.0084, odds ratio (OR)=1.15). When we analyzed effects of rs12425791 on ischemic stroke subtypes, rs12425791 was significantly associated with both small-artery occlusion (P=0.015, OR=1.15) and large-artery atherosclerosis (P=0.024, OR=1.19). Rs11833579 showed no association with atherothrombotic stroke or its subtypes in our population. Our data suggest that rs12425791 on chromosome 12p13 is a genetic marker for atherothrombotic stroke in multiethnic population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the impact of metabolic syndrome (MetS) defined by various criteria on the occurrence of ischemic stroke subtypes in a general Japanese population. Methods: A total of 2452 residents of a Japanese community, Hisayama, aged 40 years or older, were followed up for 14 years. To define MetS, we used the original Japanese criteria, the modified Japanese criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program''s Adult Treatment Panel III (NCEP) criteria, and the modified NCEP criteria. We substituted a waist circumference of ≥90cm in men and ≥80cm in women for the values of ≥85cm and ≥90cm, respectively, in the modified Japanese criteria and for >102cm and >88cm, respectively, in the modified NCEP criteria. Results: Only MetS defined by the modified Japanese criteria showed a significant association with the development of lacunar infarction, and its hazard ratios (HRs) for the development of atherothrombotic and cardioembolic infarction were significant and greater than those of MetS defined by the other criteria: adjusted HRs for lacunar, atherothrombotic and cardioembolic infarction were 1.94 (95% confidence interval (CI), 1.13–3.32; P =0.02), 2.55 (95% CI, 1.25–5.18; P =0.01) and 3.94 (95% CI, 1.89–8.22, P <0.001), respectively, after adjustment for confounding factors. Conclusion: Our findings suggest that MetS defined by the Japanese criteria with the modification of a waist circumference of ≥90cm in men and ≥80cm in women is a better predictor of each ischemic stroke subtype in the Japanese population. [Copyright &y& Elsevier]

Objective: We examined whether metabolic syndrome predicts incident type 2 diabetes more effectively than impaired fasting glucose (IFG) in a general Japanese population.Research Design and Methods: A total of 1,935 nondiabetic subjects aged 40-79 years were followed-up prospectively for a mean of 11.8 years.Results: During the follow-up, 286 subjects developed type 2 diabetes. Compared with those without metabolic syndrome, the multivariate-adjusted hazard ratio (HR) for incident type 2 diabetes was significantly higher in subjects of both sexes with metabolic syndrome, even after adjustment for confounding factors, age, family history of diabetes, total cholesterol, alcohol intake, smoking habits, and regular exercise (men: HR 2.58 [95% CI 1.85-3.59]; women: 3.69 [2.58-5.27]). The multivariate-adjusted HR of metabolic syndrome for type 2 diabetes was slightly lower in men and similar in women compared with that of IFG. The multivariate-adjusted HR for type 2 diabetes rose progressively as the number of metabolic syndrome components increased in both subjects with and without IFG. In stratified analysis, the multivariate-adjusted risk of type 2 diabetes was significantly higher in subjects with metabolic syndrome alone (2.37 [1.45-3.88]) or IFG alone (3.49 [2.57-4.74]) and markedly increased in subjects with both metabolic syndrome and IFG (6.76 [4.75-9.61]) than in subjects with neither metabolic syndrome nor IFG. Furthermore, the multivariate-adjusted risk for type 2 diabetes was also significantly higher in subjects with both metabolic syndrome and IFG than in those with either one alone (both P < 0.001).Conclusions: Our findings suggest that metabolic syndrome significantly increases the risk of incident type 2 diabetes, independent of IFG, and is therefore a valuable tool to identify individuals at high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We examined whether metabolic syndrome predicts incident type 2 diabetes more effectively than impaired fasting glucose (IFG) in a general Japanese population. RESEARCH DESIGN AND METHODS-- A total of 1,935 nondiabetic subjects aged 40-79 years were followed-up prospectively for a mean of 11.8 years. RESULTS -- During the follow-up, 286 subjects developed type 2 diabetes. Compared with those without metabolic syndrome, the multivariate-adjusted hazard ratio (HE) for incident type 2 diabetes was significantly higher in subjects of both sexes with metabolic syndrome, even after adjustment for confounding factors, age, family history of diabetes, total cholesterol, alcohol intake, smoking habits, and regular exercise (men: HR 2.58 [95% C[ 1.85-3.59]; women: 3.69 [2.58-5.27]). The multivariate-adjusted HR of metabolic syndrome for type 2 diabetes was slightly lower in men and similar in women compared with that of IFG. The multivariate-adjusted HR for type 2 diabetes rose progressively as the number of metabolic syndrome components increased in both subjects with and without 1FG. In stratified analysis, the multivariate-adjusted risk of type 2 diabetes was significantly higher in subjects with metabolic syndrome alone (2.37 [1.45-3.88]) or IFG alone (3.49 [2.57-4.74]) and markedly increased in subjects with both metabolic syndrome and IFG (6.76 [4.75-9.61]) than in subjects with neither metabolic syndrome nor IFG. Furthermore, the multivariate-adjusted risk for type 2 diabetes was also significantly higher in subjects with both metabolic syndrome and IFG than in those with either one alone (both P < 0.001). CONCLUSIONS--Our findings suggest that metabolic syndrome significantly increases the risk of incident type 2 diabetes, independent of 1FG, and is therefore a valuable tool to identify individuals at high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The association between the E23K polymorphism of ATP-sensitive K[sup +] channel subunit Kir6.2 and diabetes has been reported in Caucasians but not in Asians. We examined this issue in follow-up and cross-sectional studies in a general Japanese population. RESEARCH DESIGN AND METHODS--In a 14-year follow-up study of 976 subjects aged 40-79 years with normal glucose tolerance (NGT), we investigated the impact of the E23K polymorphism on change of glucose tolerance status using a 75-g oral glucose tolerance test. Additionally, we confirmed this association in a cross-sectional survey of 2,862 subjects. RESULTS--In the follow-up study, the frequencies of the K/K genotype or K-allele were significantly higher in subjects with conversion from NGT to diabetes than in those in whom NGT was maintained (genotypes, P = 0.01; alleles, P = 0.008). In multivariate analysis, the risk for progression to diabetes was significantly higher in subjects with the E/K (odds ratio 2.10 [95% CI 1.16-3.83]) and K/K (2.40 [1.01-5.70], P for trend = 0.01) genotypes than in those with the E/E genotype after adjustment for confounding factors, namely, age, sex, fasting plasma glucose, family history of diabetes, BMI, physical activity, current drinking, and current smoking. In the cross-sectional study, the frequencies of the K/K genotype or K-allele were also significantly higher in those with diabetes than in those with NGT (genotypes, P = 0.006; alleles, P = 0.001). CONCLUSIONS--Our findings suggest that the Kir6.2 E23K polymorphism is an independent genetic risk factor for diabetes in the general Japanese population. Diabetes 56:2829-2833, 2007 [ABSTRACT FROM AUTHOR]

Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 × 10−7, crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCη was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction. [ABSTRACT FROM AUTHOR]

Objective: We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population.Research Design and Methods: A total of 1,759 Japanese subjects, aged 40-79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years.Results: During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects.Conclusions: Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS -- A total of 1,759 Japanese subjects, aged 40-79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years. RESULTS -- During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects. CONCLUSIONS -- Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

Chronic kidney disease and cardiovascular disease in a general Japanese population: The Hisayama Study. Background. Chronic kidney disease has been shown to be an independent risk factor for cardiovascular disease in high-risk populations. However, this relationship is inconclusive in community-based populations. Methods. To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease. Results. During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) ( P< 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) ( P< 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men[hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15). Conclusion. Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population. [ABSTRACT FROM AUTHOR]

Objective:This study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential. Methods:Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation. Results:Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104 (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation. Conclusions:RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance. [ABSTRACT FROM AUTHOR]

Background: Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population.Methods: This is a cross-sectional survey of 3,113 community-dwelling individuals aged 40 years or over. MetS was defined according to the joint interim statement. MetS was diagnosed when a subject had three or more of the following components: 1) central obesity (waist circumference ≥ 90 cm for men, ≥ 80 cm in for women); 2) elevated blood pressure (≥ 130/85 mmHg or current use of antihypertensive medication); 3) hypertriglyceridemia (≥ 1.7 mmol/L); 4) low HDL cholesterol (< 1.0 mmol/L for men, < 1.3 mmol/L for women); and 5) elevated fasting plasma glucose (≥ 5.55 mmol/L or current use of antidiabetic medication). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The age- and multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using a logistic regression model.Results: Elevated depressive symptoms were observed in 4.3% of male and 6.3% of female participants. In men, the age-adjusted prevalence of elevated depressive symptoms was significantly higher in subjects with MetS than in those without (7.1% versus 3.6%, p = 0.04). The prevalence of elevated depressive symptoms rose progressively as the number of MetS components increased (3.5%, 3.6%, 5.8%, and 9.2% in male subjects with 0-1, 2, 3, and ≥ 4 components, respectively; p = 0.02 for trend). This association remained significant even after adjustment for age, marital status, history of cardiovascular disease, smoking habit, alcohol intake, and regular exercise. In women, on the other hand, there was no clear association between MetS and depressive symptoms.Conclusions: MetS was associated with elevated depressive symptoms in a general population of Japanese men. [ABSTRACT FROM AUTHOR]