小谷 和彦

Background: Evidence of the long-term benefits of telephone-delivered lifestyle interventions is limited. This study investigated the ability of telephone-delivered lifestyle intervention to reduce the incidence of metabolic syndrome (MetS) in subjects diagnosed with impaired fasting glucose (IFG) during health checkups. Methods: Our subjects were participants in the Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a prospective, cluster-randomized controlled trial designed to investigate whether goal-focused lifestyle coaching over the telephone can effectively reduce the incidence of type 2 diabetes development in high-risk individuals in a primary health care setting. We extracted 753 and 844 J-DOIT1 participants from the intervention and controls arms, respectively, who had IFG but did not meet the MetS criteria at baseline. The intervention arm received goal-focused lifestyle support delivered by health care providers via telephone over a 1-year period. The endpoint was the development of incident MetS, defined based on the Adult Treatment Panel III criteria modified for Japan. Results: During the median follow-up period of 4.9 years, 8.0% of the intervention arm and 12.0% of the control arm developed MetS. Overall, the hazard ratio (HR) for the development of MetS was 0.75 [95% confidence interval (CI), 0.52-1.09; P = 0.14] in the intervention arm. However, the HR in overweight or obese [body mass index (BMI) ≥23 kg/m2] individuals was significantly reduced to 0.63 (95% CI, 0.41-0.95; P = 0.029), but not in lean (BMI <23 kg/m2) individuals. Conclusion: Telephone-delivered lifestyle intervention effectively reduced the incidence of MetS in overweight and obese subjects in a real-world setting. Clinical trial registration number: UMIN000000662 (registered March 30, 2007; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000000798).

High density lipoproteins (HDL) structure and function studies are needed to better understand the heterogeneous nature of the HDL particle, and its interaction with associated proteins such as apolipoprotein A-1 (ApoA-1), paraoxonase 1 (PON1) and the environment. Our study assesses the effects of acute inflammation on PON1 and HDL subclasses in post-surgical colorectal cancer patients. PON1 was measured kinetically through its arylesterase and lactonase activity and HDL sub-classes were measured using Quantimetrix Lipoprint® System. White blood cells (WBC) counts, c-reactive protein (CRP) and serum amyloid A (SAA) levels were also analyzed using standard techniques. Our findings show that baseline PON1 activity is lower in colorectal cancer patients and significant reductions are observed in the acute inflammatory state post-surgery. PON1 changes are also inversely related to inflammatory markers such as SAA and CRP. In addition, our preliminary findings show that small and intermediate HDL decreases post-op Day 1. In conclusion, our study demonstrates the effects of chronic and acute inflammation on PON1. Specifically, PON1 arylesterase and lactonase activity is lower in states of chronic inflammation and further decreased in the acute inflammatory state. Additionally, in our limited sample size, while changes in PON1 and HDL subclasses may be variable in the acute inflammatory period, small HDL decreased with a loss of PON1 activity in the subacute phase.

BACKGROUND: Adult height can serve as a disease marker. While taller stature has been reported to be linked to a decreased risk of cardiovascular disease (CVD), an influence of the height on CVD is not fully understood in specific populations of Asia, which has a lower incidence of CVD and lower stature than Western populations. METHODS: We conducted a systematic review using original articles of prospective cohort studies published in English, via the PubMed database, on the relationship between the height and mortality of CVD, including cerebrovascular disease, in Asian people. RESULTS: We selected four studies on heart/coronary disease and five studies on cerebrovascular disease. Regarding heart/coronary disease, two studies showed that taller stature was associated with a decreased mortality of heart disease in men or cardiovascular disease in women. The hazard ratios of other studies had not shown a clear significance but a decreased direction of taller stature to the mortality. Regarding cerebrovascular disease, most studies showed that taller stature was associated with a decreased mortality of total cerebrovascular diseases or stroke. In two studies, taller stature showed a decreased mortality of ischemic or hemorrhagic stroke. CONCLUSIONS: Overall, adult height may be inversely predictive to the mortality of CVD, in particular cerebrovascular disease, in Asian people. While this seems to be a similar trend to that of Westerns, further studies are warranted.

BACKGROUND: Counting breaths for a full minute for all patients to determine breathing frequency could result in excessive work load for many medical staff. The aim of this study was to verify the agreement of 2 quick screening methods with counting breaths for a full minute. METHODS: We conducted a cross-sectional study to compare the breathing frequency estimates from a 15-s period multiplied by 4 (15-s quadruple) and a value which is 60 divided by the time measured for a single breath (ie, breathing time measurement) against counting breaths for a full minute. Subjects of this study included 58 nurses; 1 nurse acted as the patient, and 57 nurses counted the patient's breathing frequency using each of the 3 methods. Each nurse examiner performed the breathing time measurement, the 15-s quadruple method, and the 1-min breath count, in that order. We performed correlation and Bland-Altman analyses between the 15-s quadruple and 1-min breath count methods, and between the breathing time measurement and 1-min breath count methods. Using paired t tests, we compared the absolute difference between the 15-s quadruple and the 1-min breath count methods to the absolute difference between the breathing time measurement and the 1-min breath count methods. RESULTS: The coefficient of correlation between the 15-s quadruple and 1-min breath count was 0.83, while the coefficient of correlation between the breathing time measurement and 1-min breath count methods was 0.90. Brand-Altman analysis indicated that the bias of 15-s quadruple method to the 1-min breath count method was -2.1 ± 2.9 SD, and the limit of agreement was ±5.6; the bias of the breathing time measurement method to the 1-min breath count method was 0.5 ± 2.6 SD, and the limit of agreement was ±5.0. There were statistically significant differences between the 15-s quadruple and 1-min breath count methods and between the breathing time measurement and 1-min breath count methods (P < .001). CONCLUSIONS: The breathing time measurement method had better agreement with the 1-min breath count method than did the 15-s quadruple method in this study setting.

Maslinic acid, derived from olive fruit, reduces pro-inflammation cytokines, which are involved in muscle fiber atrophy. Therefore, the maslinic acid ingestion may enhance the muscular response to resistance training through anti-inflammatory action. We therefore conducted a parallel, double-blind, randomized, placebo-controlled trial that examined whether a combination of maslinic acid supplementation and resistance training improve mobility functions in community-dwelling elderly persons. Over a 12-week period, 36 participants underwent moderate resistance training and are assigned to the maslinic acid supplementation (n = 17, 60 mg/day) or the placebo (n = 19) group. At baseline and at 12-weeks, we assessed body composition, grip strength, walking speed, leg strength, mobility functions, and knee pain scores. Following the 12-weeks, skeletal muscle mass, segmental muscle mass (right arm, left arm, and trunk) and knee pain score of the right leg were significantly improved in the maslinic acid group, while there was no change or parameters had worsened in the placebo group. Grip strength of the better side significantly increased only in the maslinic acid group. These results suggest that maslinic acid supplementation combined with moderate resistance training may increase upper muscle mass and grip strength, and reduce knee pain, could be effective for preventing mobility-related disability in elderly persons. Clinical trial registration number: UMIN000017207.

OBJECTIVES: To investigate oral antibiotic prescribing patterns and identify factors associated with antibiotic prescriptions, with the aim of guiding future interventions to reduce inappropriate prescribing. DESIGN: Retrospective cohort study. SETTING: Database of public health insurance claims in Kumamoto prefecture (Japan). PARTICIPANTS: Beneficiaries of the national or late elders' health insurance system between April 2012 and March 2013. MAIN OUTCOME MEASURES: Of the 7 770 481 outpatient visits, 682 822 had a code for antibiotics (860 antibiotic prescriptions per 1000 population). Third-generation cephalosporins (35%), macrolides (32%) and quinolones (21%) were the most frequently prescribed. Acute respiratory tract infections (ARTIs), including viral upper respiratory infections (URI) (22%), pharyngitis (18%), bronchitis (11%) and sinusitis (10%) were the most frequently diagnosed for antibiotic prescribing, followed by gastrointestinal (9%), urinary tract (8%) and skin, cutaneous and mucosal infections (5%). Antibiotic prescribing rates for viral URI, pharyngitis, bronchitis, sinusitis and gastrointestinal infections were 35%, 54%, 53%, 57% and 30%, respectively. In multivariable analysis for ARTIs and gastrointestinal infections, patient age (10-19 years especially), patient sex (male) and facility scale (free-standing clinics or small-scale hospital-based clinics) were associated with increased antibiotic prescribing. CONCLUSIONS: Broad-spectrum antibiotics constituted 88% of oral outpatient antibiotic prescriptions. Approximately 70% of antibiotics were prescribed for ARTIs and gastroenteritis with modest benefit from antibiotic treatment. The quality of antibiotic prescribing needs to be improved. Antimicrobial stewardship interventions should target ARTIs and gastroenteritis, as well as young patients and small-scale institutions.

BACKGROUND AND AIMS: Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear. We prospectively investigated the association between the change in oxHDL and progression of CAC in a substudy of a multicenter study. METHODS: In the principal study, patients with a CAC score of 1-999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed tomography and a blood test were performed at baseline and at the 1-year follow-up. In the principal study, the increase in CAC did not differ among treatment groups. In this substudy, patients were divided into two groups: CAC progression (change in Agatston score of >0) and no CAC progression. RESULTS: In total, 140 patients were analyzed. The oxHDL level significantly decreased from 167 (132-246) at baseline to 122 (103-149) after treatment (median [25th-75th percentile], U/ml) (p < 0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r = 0.17, p = 0.04), triglycerides (r = 0.17, p = 0.04), and high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; p = 0.04). CONCLUSIONS: The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for atherosclerosis prevention.

© 2018 National Kidney Foundation, Inc. Rationale & Objective: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design: Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations: 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction: Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results: The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations: Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

A 55-year-old male presented with abdominal pain that had begun about 5 days ago. Physical examination revealed oral aphtha, genital aphthosis, and pseudofolliculitis, and the patient was diagnosed with incomplete Behçet's disease (BD). Contrast-enhanced computed tomography (CECT) showed dilation of the superior mesenteric artery and mesenteric infiltration of inflammation, indicating vasculo-BD. The symptoms were improved by 3-day of intravenous methylprednisolone pulse therapy followed by oral prednisolone. A literature review suggested that vasculo-BD should be included as a differential diagnosis in cases with unexplained abdominal pain, arterial dilation, and mesenteric invasion, and CECT examination and steroid therapy should be considered.

Background: Metabolic syndrome (MetS) and cancer are major public health problems worldwide. The relationship between MetS and cancer death is of great interest. We examined the predictive value of MetS for cancer mortality in Japan. Methods: Study participants included 4495 men and 7028 women aged 18-90 years who were registered between 1992 and 1995 as part of the Jichi Medical School Cohort Study. We used a definition of MetS modified for the Japanese population. The primary outcome was cancer mortality. Additionally, the relationship between MetS and cancer-type specific mortality was examined. Analyses were conducted with Cox's regression models adjusted for age, smoking status, alcohol drinking status, marital status, educational attainment, physical activity, occupational category, and menopausal status (only in women). Results: During a mean follow-up of 18.5 years, 473 men and 297 women died from cancer. MetS was positively associated with cancer mortality in women (hazard ratio [HR], 1.69; 95% confidence interval [CI] 1.21-2.36), but not in men (HR, 1.21; 95% CI 0.90-1.62). Additionally, MetS was associated with a high risk of colorectal (HR, 3.48; 95% CI 1.68-7.22) and breast (HR, 11.90; 95% CI 2.25-62.84) cancer deaths in women. Conclusion: MetS was a significant predictor of cancer mortality in women.

Objectives: The fasting plasma glucose/hemoglobin A1c ratio is considered a marker associated with glucose metabolism disorders, including fasting hyperglycemia. However, it remains unclear whether this ratio can be used for the prevention of deaths in individuals with normal fasting plasma glucose levels. This study aimed to see the predictive value of the fasting plasma glucose/hemoglobin A1c ratio for all-cause mortality in a general population with normal fasting plasma glucose levels. Methods: The study investigated prospectively a cohort of 1087 multi-regional, community-dwelling Japanese participants (women, 69.2%) for a follow-up period of 11.3 years. We included individuals with fasting plasma glucose levels <6.11 mmol/L and excluded those meeting the diabetes criteria. All-cause mortality was the primary outcome and hazard ratios were calculated using the Cox proportional hazard model after dividing the fasting plasma glucose/hemoglobin A1c ratios into tertiles. Results: There were 54 deaths (25 women) during the follow-up period. The high tertile group had a significantly higher hazard ratio for all-cause mortality than the low tertile group in women (multivariate-adjusted hazard ratio = 4.45; 95% confidence interval = 1.26-15.72), but not clearly in men. Conclusion: The data of the population-based cohort study suggest that a high fasting plasma glucose/hemoglobin A1c ratio can predict all-cause mortality in women with normal fasting plasma glucose levels.

INTRODUCTION: In the clinical setting, the diagnosis of neurosarcoidosis in patients with central diabetes insipidus (CDI) is typically based both on symptoms (i.e. polydipsia or polyuria) and brain magnetic resonance imaging (MRI) findings (e.g. pituitary abnormality). However, inconsistent changes in the patient's symptoms and brain MRI findings may occur during the clinical course of the disease. This review was performed to summarise the relationship between symptoms and brain MRI findings in previously reported cases of neurosarcoidosis with CDI. MATERIAL AND METHODS: Case studies of patients diagnosed with neurosarcoidosis with CDI were collected via a PubMed search of studies published through 30 June 2018. RESULTS: Thirteen eligible studies were reviewed (20 patients; 12 men, 8 women; mean age 33 years). Polydipsia or polyuria was the first symptom in 13 patients. The mean duration from disease onset to diagnosis was 3.4 months. Brain MRIs showed abnormal findings in the hypothalamus and pituitary for 17 patients. Immunosuppressive drugs were used in 17 patients. For 14 patients, MRI findings improved, while symptoms did not. CONCLUSION: Patients with both neurosarcoidosis and CDI symptoms often do not improve, despite the fact that brain MRI findings often improve following treatment. More studies involving detailed pathological analyses and longer follow-up periods are necessary.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-aged women. While PCOS is associated with an increased risk of obesity and insulin resistance, little is known regarding the prevalence of and risk factors for nonalcoholic fatty liver disease (NAFLD) among Japanese women with PCOS. We estimated the prevalence of and risk factors for elevated liver enzymes, as the index of NAFLD, in Japanese women with PCOS. Methods: We retrospectively reviewed 102 reproductive-aged women who visited the Department of Gynecology, Kyoto Medical Center in Japan from January 2000 to September 2016. Inclusion criterion was confirmed diagnosis of PCOS using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10) codes. Exclusion criteria were women with a history of liver diseases, missing body mass index (BMI) and serum alanine aminotransferase (ALT) data, and pregnancy. Data regarding age; BMI; and levels of blood glucose, serum lipid, liver enzymes, and sex hormones were obtained from medical records. Elevated liver enzymes was defined as ALT > 19 IU/L. Optimal cutoffs for risk factors for elevated liver enzymes were calculated to determine predictors of elevated liver enzymes using area under the curve (AUC) by receiver-operating characteristics (ROC). Results: The prevalence of elevated liver enzymes was 33.3%. BMI was significantly higher in PCOS patients than in those without elevated liver enzymes (25.3 vs. 20.7 kg/m2, P < 0.05). ROC analyses were performed using BMI and blood glucose and testosterone levels because BMI and blood glucose showed differences between the groups and testosterone is related to fatty liver. AUC of the model including BMI and blood glucose and testosterone levels was 0.861 (sensitivity, 66.7%; specificity, 100%). Conclusions: These findings suggest that elevated liver enzymes are common in women with PCOS. An algorism using BMI and blood glucose and testosterone levels might be useful to determine elevated liver enzymes in women with PCOS. Our finding may be useful for the study of NAFLD among Japanese women with PCOS since several previous studies have indicated elevated liver enzymes to be related to the potential presence of NAFLD. Further examination, including abdominal ultrasonography and/or liver biopsy data, is required to confirm these results.

Background: The aims of this study were (a) to ascertain age-related changes in the reference values in hematological and serum biochemical examinations of beagles, and (b) to clarify the changes in these findings, including acute phase proteins and oxidative stress, throughout pregnancy and after parturition. Methods: Clinicopathological parameters were measured in young beagles at 6, 9 and 12 months and in adult beagles aged from 24 to 60 months. Likewise, pregnant beagles were investigated throughout the pregnancy and after parturition. Results: Apparent age-related changes were found in erythrocytic parameters during the growth and development of beagles. Most of the parameters (total protein, albumin, blood urea nitrogen, creatinine, urate, alkaline phosphatase (ALP) and creatine kinase (CK) exhibited age-dependent transitions. White cell count significantly increased after 30 days of pregnancy. The values of erythrocytic parameters moderately decreased during the second half of the pregnancy. Triglycerides, total cholesterol, free cholesterol and phospholipid concentrations increased in the mid- and late stages of pregnancy. ALP, lactate dehydrogenase, CK and cholinesterase activities markedly increased during pregnancy and/or after parturition. C-reactive protein (CRP) concentrations gradually increased and reached a maximum after 30-40 days of pregnancy. Serum amyloid A (SAA) levels markedly increased at 30 days of pregnancy before subsiding, and then increased again 3 days after parturition. Reactive oxygen metabolites (d-ROMs) showed significant increases after 30 and 40 days of pregnancy. Conclusions: Reference values for hematological and serum biochemical examinations should be used for health evaluation of dogs, taking sex, age and the stage of pregnancy into consideration. Measurements of CRP, SAA and d-ROM levels are also useful for assessing maternal conditions in mid-pregnancy.

RATIONALE: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. OBJECTIVE: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. METHODS AND RESULTS: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (β=0.10; P=0.020) and oxHDL (β=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03). CONCLUSIONS: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor-C ( VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF -C value may independently predict all-cause mortality.

BACKGROUND: The board certification system serves as a quality assurance system for physicians, and its design and operation are important health policy issues. In Japan, board certification was established and operated independently by academic societies and has not been directly linked to reimbursement systems. The phenomenon of younger physicians seeking specialist careers has raised concerns about acceleration of the tendency of fewer physicians working in rural areas and the maldistribution of physicians. Little is known about the associations between physicians' geographical migration patterns and board certification status changes or between the continuation of urban/rural practice and the maintenance of board certification. This study aimed to identify these associations and to discuss their policy implications. METHODS: We analyzed 2012 and 2014 data from the Survey of Physicians, Dentists, and Pharmacists, a national census survey. To analyze geographical migration patterns, transitions in practice location (rural, intermediate, and urban) were analyzed by board certification status change (new, lost, consistently certified, and consistently uncertified). Logistic regression analysis was conducted to assess whether the odds of migrating to more urban/rural municipalities were associated with board certification status changes, adjusting for covariates, and whether practicing in a rural area was associated with maintaining board certification. RESULTS: Among 18,726 newly board-certified physicians, 94.9% (13,435/14,150) of those working in urban areas before certification remained in urban areas, whereas 64.6% (393/608) of those working in rural areas stayed in rural areas. Those who were newly certified had higher odds of moving to more urban areas, adjusting for covariates. Those who stayed in rural areas showed lower odds of maintaining board certification, adjusting for covariates. CONCLUSIONS: Newly board-certified physicians are more likely to migrate to other types of areas, particularly more urban areas, than other physicians. Allocating more training quotas to rural areas could be one option for leveling the distribution of specialists. It also appeared that those practicing in rural areas have difficulty maintaining their certification, so the need to establish a support system for already-certified physicians in rural areas should be emphasized.

BACKGROUND AND OBJECTIVES: The Kumamoto earthquakes struck Kumamoto prefecture, in the southwest part of Japan in April 2016. Physical and mental disorders presenting to hospital increased after the 2016 Kumamoto earthquakes. Impaired access to primary care due to the earthquakes may have contributed to this increase. However, it is not known whether the 2016 Kumamoto earthquakes affected access to primary care. The objective of the present study was to investigate the impact of the 2016 Kumamoto earthquakes on short-term health conditions by analysing ambulatory care sensitive conditions (ACSCs), using administrative data from Kumamoto prefecture. DESIGN: A retrospective cohort study. SETTING: Residents enrolled in National Health Insurance or Late Elders' Health Insurance from Kumamoto prefecture, Japan. PARTICIPANTS: All hospital admissions due to ACSCs between 15 March and 16 May in each year from 2013 to 2016. OUTCOME MEASURES: ACSCs are defined as conditions for which appropriate primary care interventions could prevent admission to the hospital. RESULTS: We identified a total of 7921, 18 763 and 85 436 admissions for vaccine, acute and chronic preventable ACSCs, respectively, during the study period. Admissions within 7 days after the 2016 Kumamoto earthquakes increased to 32.6% (10.2, 59.5), 44.1% (27.0, 63.5) and 27.7% (20.2, 35.6) for vaccine-preventable, acute and chronic ACSCs, respectively. However, admissions for ACSCs did not change significantly 30 days after the earthquakes. CONCLUSION: The 2016 Kumamoto earthquakes were associated with increased hospital admissions for ACSCs. The impact of the earthquakes on admissions for ACSCs did not persist for more than 7 days.

BACKGROUND: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. METHODS: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). RESULTS: Mean age was 29.5 years, and 53% of participants were 20-25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. CONCLUSIONS: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, inborn disruption in bile acid synthesis characterized by severe systemic xanthomas, cataracts and neurological injuries occurring before adolescence without elevation of the serum cholesterol or triglyceride levels. CTX is caused by a deficiency of the mitochondrial enzyme sterol 27-hydroxylase, which is encoded by the CYP27A1 gene. We herein report a 50-year-old Japanese woman with late-onset CTX who had no relevant symptoms before the development of bilateral Achilles tendon xanthomas in middle age. A genetic analysis revealed a compound heterozygous mutation in the CYP27A1 gene with a previously known missense mutation (NM_000784.3:c.1421 G>A) and a novel frame shift mutation of NM_000784.3:c.1342_1343insCACC.

BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. In Japan, the number of patients and incidence rate of KD has increased continuously since its discovery. The aim of this report was to analyze the latest nationwide epidemiological survey of KD in Japan. METHODS: The 23rd nationwide survey of KD was conducted in 2015. To report on all patients diagnosed with KD in 2013 and 2014, a questionnaire was sent to hospitals with ≥100 beds containing pediatric departments, as well as specialized pediatric hospitals. RESULTS: The number of KD patients reported was 15 696 in 2013 and 15 979 in 2014, resulting in an annual incidence rate of 302.5 and 308.0 per 100 000 population aged 0-4 years, respectively. The number of patients and incidence rate of KD in 2014 were the highest ever recorded in Japan. The number of patients diagnosed per month peaked in January, and a gradual increase in summer was also observed. Eight patients died of KD in 2013 and 2014. CONCLUSIONS: The number of patients and incidence rate of KD in Japan continue to increase. Continued surveillance of epidemiological trends of KD is therefore required.

Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0<CAC progression ≦100; 7.7%, and CAC progression >100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p=0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) >30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.

Background: The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. Objective: We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. Methods: We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40–89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04–1.55 mmol/L (40–59 mg/dL) using a cohort-stratified Cox proportional hazards model. Results: During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37–4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. Conclusion: We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts.

Background: Advanced glycation end products (AGEs) are associated with diabetes mellitus. Digested food-derived AGEs have been implicated in the pathogenesis of AGE-related disorders, and restricting diet-derived AGEs improves insulin resistance in animal models. The AGE content in foods changes according to cooking method, and it is higher in baked or oven-fried foods than in those prepared by steaming or simmering. Here, we examined the feasibility of crossover comparison tests for determining how different cooking methods (normal diet vs. low-AGE diet) affect insulin levels in non-diabetic Japanese subjects. Methods: Five adult men and women (age, 41 ± 7 years; body mass index (BMI), 21.7 ± 2.6 kg/m2) were enrolled. The following dietary regimen was used: days 1 - 3, control meal; day 4, test meal (normal diet vs. low-AGE diet); day 5, washout day; and day 6, test meal. On days 4 and 6, blood samples were collected before and at 2, 4, and 6 h after meals. Results: Blood levels of N-(carboxymethyl) lysine (CML) increased with dietary intake, but the increase was similar for the normal diet and low-AGE diet groups. Mean plasma glucose, insulin, triglycerides (TG), and CML did not differ significantly between the two groups. The area under the curve (AUC) for insulin levels was lower in the low-AGE diet group (d = 0.8). The sample size calculated from the effect size of the insulin AUC change was 22. Conclusions: Twenty-two subjects may be needed to investigate the changes in clinical parameters attributable to cooking method in non-diabetic Japanese subjects.

BACKGROUND: In Japan, although many suicidal studies were previously conducted in tertiary emergency department (ED) settings, no published studies have reported on suicidal patients presenting to the secondary EDs. The aim of the study was to describe the characteristics of suicidal patients and the referral rates to a psychiatrist overall and by type of facility. METHODS: Questionnaires were sent to all secondary and tertiary EDs in Tochigi prefecture, Japan. Data were collected for cases who presented in September 2009. Chi-square, Fisher's exact, and t-tests compared the results by gender and type of ED. RESULTS: All 74 EDs responded to the survey. There were 81 patients who attempted or died by suicide (36 men and 45 women). The most common method of suicide attempt was drug overdose (57%) followed by stabbing (17%). About a half used prescription drugs to attempt or die by suicide. The majority had a history of psychiatric disorders, and 35% had previous suicide attempt. About a half were admitted to medical or surgical unit; 33% were discharged home; and 9% died. After excluding those who died, 53% were referred to a psychiatrist, but 47% were not referred to a psychiatrist. The referral rate was lower for cases seen at secondary EDs (38%) compared to tertiary EDs (67%). CONCLUSION: Although professional organizations suggest that suicidal patients are seen by a psychiatrist, many were not, especially at secondary EDs. Further research is needed to assure that suicidal patients presenting to EDs receive appropriate psychiatric assessment and follow-up after discharge.

The Committee on Plasma Protein of the Japan Society of Clinical Chemistry performed a study on the standardization of antistreptolysin-O (ASO) measurement based on the lack of certified standards. First, the present status of variation in ASO values among commercial kits was assessed. The measurements of 5 pooled sera with different values revealed that 4 out of 8 kits were in high agreement. Based on these results, the pooled sera, for which the ASO value was calculated as the mean measurement from the 4 kits, was defined as a candidate reference for ASO measurement. Commutabiity studies using the candidate sera and 70 patient sera produced satisfactory results with the 6 kits examined. In conclusion, this committee proposed that this candidate should be utilized as a reference until an appropriate standard is available. The value of the reference and its uncertainty are 198.15 IU/mL and 9.018 IU/mL, respectively.

Background: The aim of the study was to observe the changes in blood oxidative stress levels by oral contraceptive (OC) and/or dydrogesterone (DG) treatment. Methods: A retrospective cohort of 27 premenopausal women with primary dysmenorrhea consisted of the OC treatment group (N = 17) and the DG treatment group (N = 10) by choice of the initial treatment. The OC group included two subgroups: patients with continuous OC treatment (treated for at least 15 months, N = 10) and patients with discontinuous OC treatment (switched to DG treatment after approximately 6 months of initial OC treatment: N = 7). The DG group had 15 months of continuous DG treatment. Blood parameters, including diacron-reactive oxygen metabolites (d-ROMs: an oxidative stress marker), were measured. Results: The d-ROMs level was elevated in the OC group 3 months after initial treatment (mean: from 321 (at baseline) to 512 Carratelli Units (Carr U); P < 0.01), while such changes were not observed in the DG group. The d-ROMs level was reduced in the discontinuous OC subgroup 15 months after initial treatment (from 508 (3 months after initial treatment) to 372 Carr U; P < 0.01), while such changes were not observed in the continuous OC subgroup. The DG group displayed unchanged the d-ROMs level. Conclusion: Replacing OC with DG can attenuate oxidative stress as elevated by OC, thereby alleviating the possible vascular risks with OC treatment.

Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies indicated that serum CPP levels were increased with decline of renal function and associated with inflammation and vascular calcification. However, CPP assays used in these studies measured only a part of CPP over a certain particle size and density. Here we show that such CPP are mostly artifacts generated during processing of serum samples in vitro. The native CPP in fresh plasma are smaller in size and lower in density than those artifactual CPP, composed of fetuin-A carrying amorphous and/or crystalline calcium-phosphate, and increased primarily with serum phosphate levels. We have identified several physicochemical factors that promote aggregation/dissolution of CPP and transition of the calcium-phosphate from the amorphous phase to the crystalline phase in vitro, including addition of anti-coagulants, composition of buffer for sample dilution, the number of freeze-thaw cycles, the speed for sample freezing, and how many hours the samples were left at what temperature. Therefore, it is of critical importance to standardize these factors during sample preparation in clinical studies on CPP and to investigate the biological activity of the native CPP.

BACKGROUND: Although diabetes mellitus is a risk factor for cancer, the relationship of an increased glucose concentration at a non-diabetic glucose level with cancer mortality is yet to be determined. OBJECTIVE: The aim was to observe whether an increased glucose concentration and/or glucose intolerance at the non-diabetic glucose level can predict cancer mortality. METHODS: Population-based prospective cohort studies evaluating cancer mortality at the non-diabetic level (defined as fasting plasma glucose <7.0 mmol/L and two-hour plasma glucose <11.1mmol/L following an oral glucose tolerance test) were collected via a PubMed search with an additional Google scholar search between 1 January 1966 and 31 July 2016. RESULTS: We identified seven studies, which met the defined criteria. Studies examining fasting/casual states indicated an increase in cancer mortality with a slight increase in fasting/casual glucose levels in men in particular. Not all, but some studies using a glucose tolerance test indicated an increase in cancer mortality with impaired glucose tolerance/prediabetes. Concerning cause-cancer mortality, glucose intolerance states appeared to have an increase in mortality, particularly due to the stomach, liver and pancreatic cancers. CONCLUSION: In these studies reviewed, cancer mortality increased in individuals with an increased glucose concentration and an increased potential was seen in those patients with glucose intolerance even at non-diabetic glucose levels. The outcome of these findings is promising and forms the basis for further studies to directly address the relevance of increased (non-diabetic) glucose and glucose intolerance as a prognostic indicator of cancer mortality.

PURPOSE: The purpose of this study was to clarify the effect of ultrasonic irradiation on biofilm produced by Staphylococcus epidermidis (S. epidermidis), which causes central venous catheter-related infections. MATERIALS AND METHODS: Staphylococcus epidermidis (S. epidermidis, ATCC 35984 RP 62A) was used in this study. First, biofilm was prepared from S. epidermidis on the bottom of the upper left well of a 6-well plate. Next, the biofilm was irradiated for 24 h with 1-MHz ultrasound (US) in the continuous wave mode to serve as the US irradiation group. The acoustic power irradiated below the bottom of the well was 3.8 mW. As a control (non-US irradiation group), non-irradiated biofilm on the bottom of a 6-well plate was incubated at 37 °C in an atmosphere of 5.0% CO2. After US irradiation, the bottoms of the wells were stained with 0.1% crystal violet for 60 s. To extract the crystal violet, 99.5% ethanol was added to the wells, and the extracted solutions were measured at an absorbance of 595 nm. RESULT: The absorbance of the US irradiation group was significantly less than that of the non-US irradiation group (p < 0.01). CONCLUSION: US irradiation can decrease the amount of S. epidermidis biofilm when the duration of US irradiation is sufficiently long even if the acoustic intensity is low.

BACKGROUND: Although the incidence rates of Kawasaki disease (KD) in Japan have been determined in nationwide surveys, the cumulative incidence, that is, the proportion of those with a history of KD in the general population of 10-year-olds, is currently unknown. The aim of this study was therefore to assess the cumulative incidence of KD in Japan. METHODS: Using the age- and sex-specific incidence rate of KD in Japan from the results of the nationwide surveys, incidence probabilities, that is, the age-specific number of KD patients divided by the population used in the vital statistics, and cumulative proportions of those not affected by KD up to the end of 9 years of age, were calculated. The cumulative incidence was then defined as 1 minus the cumulative proportion. The observed age classes were 0, 1, 2, 3, 4, and 5-9 years. All data were calculated by sex. RESULTS: The cumulative incidence was 0.004833 for boys and 0.003474 for girls in 1991, but was 0.015284 and 0.012145 in 2014, respectively. According to these figures, 15.284 per 1,000 boys and 12.145 per 1,000 girls have been affected by KD by the age of 10 years. The birth-cohort cumulative incidences had similar trends. CONCLUSIONS: More than 10 persons in 1,000 have a history of KD at age 10 years in Japan.

Physical activity improves various metabolic disturbances. The effect of physical activity on non-alcoholic fatty liver disease (NAFLD) has not been defined, particularly in athletes who are able to consume a diet to increase body mass. The aim of this study was to evaluate the prevalence of NAFLD and associated factors of NAFLD among male university rugby football players [n = 69, 37 forwards (FW) and 32 backs (BK)], relative to age-matched controls (CON; n = 29). For FW players exercise consists of physical contact play, such as ruck, mall, scrum, and tackle. For BK players exercise consists of sprints and endurance running. Liver function tests and bioimpedance analysis to assess body composition were performed. Subjects consuming ≤ 20 g/day of ethanol and exhibiting an aspartate transaminase (AST) level ≥ 33 U/L, and/or alanine transaminase (ALT) level ≥ 43 U/L, were considered to have NAFLD. The PNPLA3 and MTP genotypes were determined using real-time polymerase chain reaction (PCR). The body mass index, body fat mass, and lean body mass were significantly higher in the FW group than in the BK and CON groups (P < 0.05). The total cholesterol, low-density lipoprotein cholesterol, triglyceride, AST, ALT, and alkaline phosphatase levels were significantly higher in the FW group than in the CON group (P < 0.05). The prevalence of NAFLD was significantly higher in the FW group than in the BK group and CON group (18.9, 8.6, and 0.0%, respectively), whereas there were non-significant between-group differences in the frequency of the PNPLA3 and MTP genotypes. These findings indicate that rugby football players, especially those in the FW position, are at higher risk of developing NAFLD, which emphasizes the role of diet and exercise in the development of NAFLD.

BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein A-I is associated with the pathogenesis of Alzheimer's disease (AD). HDL particle size is modified in the presence of pathological conditions, while the significance of the HDL particle size remains controversial. OBJECTIVE: The aim of this study was to investigate the HDL lipoprotein subclasses in mild cognitive impairment (MCI) and AD. METHODS: This cross-sectional study included 20 AD patients, 17 MCI patients, and 17 age-matched controls without cognitive impairment, selected from the database of the Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia) registry. The diagnoses of AD and MCI were performed by expert neurologists according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. Serum HDL subclasses were measured by electrophoretic separation of lipoproteins using the Lipoprint System. The neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was calculated by dividing the neutrophil count by the lymphocyte count. RESULTS: Small-sized HDL particle levels in the MCI group were significantly higher than in the control group, although there was no difference in serum HDL-cholesterol levels between MCI and control groups. NLR in the MCI group was higher than in the control group, but this difference was non-significant (p = 0.09). There was no difference in HDL subclasses or NLR between the AD and control groups. CONCLUSION: These findings suggest that HDL subclasses might be associated with the development of MCI.

Exercise training ameliorates nonalcoholic fatty liver disease (NAFLD) as well as obesity and metabolic syndrome. Although it is difficult to eliminate the effects of body weight reduction and increased energy expenditure-some pleiotropic effects of exercise training-a number of studies involving either aerobic exercise training or resistance training programs showed ameliorations in NAFLD that are independent of the improvements in obesity and insulin resistance. In vivo studies have identified effects of exercise training on the liver, which may help to explain the "direct" or "independent" effect of exercise training on NAFLD. Exercise training increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression, improves mitochondrial function and leads to reduced hepatic steatosis, inflammation, fibrosis, and tumor genesis. Crosstalk between the liver and adipose tissue, skeletal muscle and the microbiome is also a possible mechanism for the effect of exercise training on NAFLD. Although numerous studies have reported benefits of exercise training on NAFLD, the optimal duration and intensity of exercise for the prevention or treatment of NAFLD have not been established. Maintaining adherence of patients with NAFLD to exercise training regimes is another issue to be resolved. The use of comprehensive analytical approaches to identify biomarkers such as hepatokines that specifically reflect the effect of exercise training on liver functions might help to monitor the effect of exercise on NAFLD, and thereby improve adherence of these patients to exercise training. Exercise training is a robust approach for alleviating the pathogenesis of NAFLD, although further clinical and experimental studies are required.

Given Japan's super-ageing society and its need for developing community-based integrated care system, the role of home care nursing is becoming increasingly important. A central concern in home care nursing is regional/spatial placement of home nursing stations and accessibility for patients. Analysis based on geographic information systems (GIS) may be useful in home care nursing research. We conducted a literature review of home care nursing research based on GIS in Japan. A total of 4 articles were selected following a search of medical literature databases. The first report was published in 2014. Most subjects in the identified studies were older people. Most studies were implemented at a municipal level. Key themes in the identified studies were "placement of specialists and home nursing stations" and "placement of home nursing stations and target patients." Despite the paucity of research, as all identified studies examined the community areas with an aged population, it may point to the need to consider community-based integrated care systems, including home care nursing, in Japan. More GIS-based research on home care nursing is called for.

Objectives: Periodontal disease is prevalent and has an inflammation associated with not only oral but also systemic pathologies. The diagnosis by biomarkers is required for clinical practice on periodontal disease. The lactoferrin and α1-antitrypsin were both inflammation-related molecules. The present study investigated the relationship between the periodontal status and the two biomarkers in gingival retention fluid (GRF). Patients and Methods: In 63 subjects with periodontitis, the GRF was sampled from maxillary anterior gingiva using a microbrush for 30 seconds. The lactoferrin and α1-antitrypsin levels in GRF were measured by an enzyme-link solvent immunoassay. Periodontal status was evaluated by probing pocket depth (PD) and bleeding on probing (BOP). Results: There was a higher level of these biomarkers in saliva (median (ng/mL), lactoferrin: 3611.9, α1-antitrypsin: 4573.3) than in GRF (lactoferrin: 61.0, α1-antitrypsin: 54.7). There was a mild-to-moderate but significantly positive correlation in lactoferrin or α1-antitrypsin between GRF and saliva. There was a positively mild-to-moderate accuracy (area under the curve: 0.60-0.81) of lactoferrin or α1-antitrypsin in GRF or in saliva to distinguish the severity of periodontal status. The cutoff level (ng/mL) of lactoferrin in GRF for detecting ≥30% of PD ≥ 4 mm (moderate periodontitis) was 68.6 and for detecting ≥20% of BOP (clinically active periodontitis) was 61.2. The cutoff level (ng/mL) of α1-antitrypsin in GRF for detecting ≥30% of PD ≥ 4 mm was 54.5 and for detecting ≥20% of BOP was 35.3. Conclusions: The data can promote an application of the measurements of lactoferrin and α1-antitrypsin in GRF to clinical practice on periodontal disease.

Objective To investigate the potential use of high mobility group box 1 (HMGB1) as a marker for the surgical course following surgery for colorectal cancer (CRC). Methods Patients with advanced CRC undergoing open colorectal surgery who did not develop postsurgical complications were enrolled in the study. Blood samples were taken preoperatively and at 1 day, 1 week and 3 weeks after surgery for the measurement of the white blood cell count, serum C-reactive protein, serum amyloid A and HMGB1. Results Data from 21 patients were analysed. HMGB1 levels changed significantly during the surgical course, increasing from a preoperative median of 6.8 ng/ml to 12.1 ng/ml at 1 day postoperatively, and then decreasing to 8.1 ng/ml at 1 week postoperatively and 4.0 ng/ml at 3 weeks postoperatively. These changes were similar to but were not completely correlated with the changes seen in the other markers. Conclusion Serum HMGB1 may be a potential marker to monitor the surgical course in patients undergoing surgery for CRC, although further studies are warranted before it can be introduced into routine clinical practice.

Common inner ear diseases include peripheral vestibular disorder (PVD) and hearing impairment. The association between smoking and peripheral vestibular disorder (PVD) is unclear. We examined associations between smoking and new PVD events. In this retrospective study, we consecutively enrolled 393 participants aged &gt;= 20 years [mean age 65.3 years; males 133 (33.8%)] treated for hypertension, dyslipidaemia, or diabetes mellitus at a primary care clinic between November 2011 and March 2013. Participants were categorized as ever-smokers (including current and past -smokers; divided per &lt; 30 and &gt;= 30 pack-years), and never-smokers. New PVD events were reported over a 1-year follow-up period. Hazard ratios (HR) for new onset PVD were estimated using the Cox proportional hazard regression model. Compared to never-smokers, the adjusted HR was 2.22 for ever-smokers and 2.70 for all ever-smokers with &gt;= 30 pack-years among all 393 participants. Among male participants, compared to never-smokers, the adjusted HR was 4.41 for ever-smokers with &gt;= 30 pack-years. A smoking history of &gt;= 30 pack-years was strongly associated with the risk of new onset PVD in males but not, females. This study may assist patients with smoking cessation for the prevention of new PVD events among males.

Background: Whereas high body mass index (BMI) is reportedly a risk factor for cardiovascular events in Western countries, low BMI has been reported as a risk factor for cardiovascular death in Asia, including Japan. Although subarachnoid hemorrhage (SAH) is a highly fatal disease and common cause of disability, few cohort studies have examined the associations between BMI and SAH in Japan. This study investigated the associations between BMI and incidence of SAH using prospective data from Japanese community residents. Methods: Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into 5 BMI groups: &lt;= 18.5, 18.6-21.9, 22.0-24.9, 25.0-29.9, and &gt;= 30.0 kg/m(2). Multivariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard model with BMI of 22.0-24.9 kg/m(2) as the reference category. Results: During the mean follow-up period of 10.8 years, 55 participants (13 men, 42 women) experienced SAH. BMI &gt;= 30.0 kg/m(2) was associated with significantly higher risk for SAH (HR, 5.98; 95% CI, 2.25-15.87). BMI &lt;= 18.5 kg/m(2) showed a nonsignificant tendency toward high risk of SAH (HR, 2.51; 95% CI,.81-7.79). Conclusions: High BMI was a significant risk factor for SAH. Lower BMI showed a nonsignificant tendency toward higher risk of SAH. Our results suggest a J-shaped association between BMI and risk of SAH incidence.

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein-coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3'-5'-cyclic adenosine monophosphate (cAMP)-dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

AIMS/INTRODUCTION: The distributer of the anti-glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti-glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants. MATERIALS AND METHODS: A total of 79 type 1 diabetes mellitus patients and 79 age-matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut-off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus. RESULTS: The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type. CONCLUSIONS: The present study suggests that both anti-glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type.

INTRODUCTION: Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with lower circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less well studied. AIMS: We aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) [Lp(a)] through a meta-analysis of available randomized controlled trials (RCTs) and observational studies. METHODS: This study was registered in the PROSPERO database (CRD42016036890). Scopus, MEDLINE and EMBASE were searched from inception until 22 March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate. RESULTS: Meta-analysis of five studies with 215 participants suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment (SMD -0.41, 95% confidence interval -0.68 to -0.14, p = 0.003). This effect was robust in the sensitivity analysis. CONCLUSIONS: Meta-analysis suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results.