Three epochs on estimating the parameter values of thermodynamic Sharpe-Schoolfield-Ikemoto (SSI) model describing the relation of temperature and insect development rate.

The SSI model describes the relationship between temperature and development rate of insect based on the laws of thermodynamics. The greatest feature of the SSI model curve is that it defines the "Intrinsic optimum temperature for the development of ectotherms". However, this model has 8 parameters, it was extremely difficult to estimate the values of these parameters from experimental data. This is because the curve fitting of experimental data yields multiple curves depending on the initial conditions. In the first epoch of estimating parameter values, the difficulties were overcome by clarifying the model and applying all the knowledge gained about the model, but it took several days to determine the model. In the second epoch, the OptimSSI-program, which incorporates a basic optimization function, was developed, making it possible to obtain parameter values instantaneously after inputting experimental data. Although this program mostly runs automatically on a PC, a manual calculation remains to be carried outs so that the obtained model curves do not deviate from Arrhenius' law. Afterward, a new program was suggested. This new program called DEoptim.sqrt not only incorporates an optimization function available on the internet but also was completely different from OptimSSI-P in terms of the design concept. Users had hoped that this new program would be start of the third epoch; however, when we examined the output values, there were serious problems, and we were back in the state before the first epoch. After all, OptimSSI-P of the second epoch was decided to be more reliable.

TOP2A, GGH, and PECAM1 are associated with hematogenous, lymph node, and peritoneal recurrence in stage II/III gastric cancer patients enrolled in the ACTS-GC study.

BACKGROUND: To identify factors related to relapse sites, we carried out an exploratory biomarker analysis of data from the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer study, which is a randomized, controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer. PATIENTS AND METHODS: Surgical specimens from 829 patients were retrospectively examined, and 63 genes involved in a variety of biological processes were analyzed by quantitative real-time PCR. Gene expression normalized to reference genes was categorized as lower or higher than the median, and association with relapse sites was analyzed based on 5-year relapse-free survival. RESULTS: Hematogenous, lymph node, and peritoneal recurrence developed in 72, 105, and 138 of the 829 patients, respectively; hazard ratios were 0.79 (95% confidential interval: 0.54-1.16), 0.51 (0.31-0.82), and 0.60 (0.42-0.84), respectively. Expression of platelet/endothelial cell adhesion molecule 1 (PECAM1) and topoisomerase II alpha (TOP2A) was strongly correlated with hematogenous recurrence and peritoneal recurrence, respectively (false discovery rate = 7.7×10-5 and 0.002, respectively). Gamma-glutamyl hydrolase (GGH) expression was moderately correlated with lymph node recurrence (false discovery rate = 0.34). Relapse-free survival was worse in patients expressing high levels of PECAM1 (hazard ratio = 2.37, 1.65-3.41), TOP2A (hazard ratio = 2.35, 1.55-3.57), or GGH (hazard ratio = 1.87, 1.13-3.08), respectively. A multivariate analysis revealed that these were stronger independent risk factors than tumor histological type. CONCLUSION: In patients with stage II/III gastric cancer, TOP2A, GGH, and PECAM1 levels in primary tumors are linked to high risk of hematogenous, lymph node, and peritoneal recurrence, respectively.

Association between Overall Lifestyle Changes and the Incidence of Proteinuria: A Population-based, Cohort Study.

Objective This study aimed to examine the association between the changes in an overall healthy lifestyle, as quantified by the number of unhealthy lifestyle factors and obesity status, and the incidence of proteinuria in the general Japanese population. Methods A retrospective cohort study was conducted among 99,404 (men, 36.9%) participants aged from 40-74 years of age who underwent two health check-ups with a 1-year interval in Japan between 2008 and 2009. Any participants with chronic kidney disease at baseline were excluded. The smoking status, body mass index, physical activity, alcohol consumption, and healthy eating habits were combined into a simple overall healthy lifestyle score ranging from 0 to 5. The changes in overall healthy lifestyle scores from baseline (range, -5 to +5) and the incidence of proteinuria, defined by a dipstick urinalysis (score ≥1+), were assessed at the second check-up. A logistic regression analysis was used to examine the association between the changes in overall healthy lifestyle scores and the incidence of proteinuria. Results After one year of follow-up, 3.9% of men and 2.4% of women developed proteinuria. Each increase (or decrease) in the changes in overall healthy lifestyle scores was associated with a reduced (or increased) risk of proteinuria in both men (odds ratio (OR) 0.87; 95% confidence interval (CI), 0.81-0.94) and women (OR 0.87; 95%CI, 0.80-0.94) after adjusting for age, baseline lifestyle scores, hypertension, diabetes mellitus, and hypercholesterolemia. Stratified analyses based on age, the presence or absence of hypertension, or diabetes mellitus revealed similar results. Conclusion Overall lifestyle changes, even within a year, were found to influence the incidence of proteinuria.

Impact of insulin-like growth factor-1 receptor and amphiregulin expression on survival in patients with stage II/III gastric cancer enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer.

BACKGROUND: Exploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone. METHODS: Formalin-fixed paraffin-embedded surgical specimens from 829 patients were retrospectively examined, and 63 genes were analyzed by quantitative real-time RT-PCR after TaqMan assay-based pre-amplification. Gene expression was normalized to the geometric mean of GAPDH, ACTB, and RPLP0 as reference genes, and categorized into low and high values based on the median. The impact of gene expression on survival was analyzed using 5-year survival data. The Benjamini and Hochberg procedure was used to control the false discovery rate. RESULTS: IGF1R and AREG were most strongly correlated with overall survival, which was significantly worse in high IGF1R patients than low IGF1R patients, but better in high AREG patients than low AREG patients. The hazard ratio for death in the analysis of overall survival (S-1 vs. surgery alone) was reduced in the high IGF1R group compared with the low IGF1R group and in the low AREG group compared with the high AREG group. There were no significant interaction effects. CONCLUSION: IGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric cancer, whereas AREG gene expression was associated with good outcomes. No significant interaction effect on survival was evident between S-1 treatment and gene expression.

Decreased serum bone specific alkaline phosphatase and increased urinary N-terminal telopeptide of type I collagen as prognostic markers for bone mineral density loss in HIV patients on cART.

OBJECTIVES: Bone mineral density (BMD) loss is a major chronic complication in HIV patients. We performed a prospective study to determine the time course of BMD changes and to find prognostic factors of BMD loss in HIV patients on combination antiretroviral therapy (cART). PATIENTS AND METHODS: Subjects were 54 male Japanese HIV patients who had been on cART ≥1 year with no therapeutic agents for osteoporosis. Patients were observed for ≥1 year (median 3.1 years) and underwent annual BMD analyses using dual energy X-ray absorptiometry. Changes in BMD at lumbar spine and femoral neck were calculated for each person-year of all the patients. Clinical factors were also collected simultaneously with BMD examinations to determine prognostic factors for BMD loss. RESULTS: In total, 173 person-years in 54 patients were observed. One third (19, 35.2%) and slightly over half (30, 55.6%) patients showed BMD decreases at lumbar spine and femoral neck, respectively. However, the median BMD changes at lumbar spine and femoral neck were 0.0% and -0.52% per year, respectively. Monovariant and mixed model analyses determined that decreased serum bone specific alkaline phosphatase (BAP, p = 0.0047) and increased urinary N-terminal telopeptide (uNTx, p = 0.0011) were prognostic factors for BMD loss at lumbar spine and femoral neck, respectively. CONCLUSIONS: BMD at both lumbar spine and femoral neck changed little on average in HIV patients on cART. Decreased serum BAP or increased uNTx may be helpful to predict progressive BMD loss in the following year and to select patients for BMD follow-up or initiation of anti-osteoporosis treatment.

Impact of the Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Incidence and Progression of CKD: A Longitudinal Study in a Large Japanese Population.

BACKGROUND: The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. PREDICTOR: Quartiles of TG:HDL-C ratio. OUTCOMES & MEASUREMENTS: Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. RESULTS: In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. LIMITATIONS: Short observation period and single measurement of all variables. CONCLUSIONS: A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population.

Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population.

Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at baseline and during 3 annual follow-up visits (4 visits). BP variability was defined as standard deviation (SD) and average real variability during the 4 visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD. In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11-1.20], 1.08 [1.04-1.12], 1.13 [1.09-1.17], 1.06 [1.02-1.10], respectively; all P<0.01) after adjustment for clinical characteristics, and with mean BP from year 0 to year 3. The associations of SDBP and average real variabilityBP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06-1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive medication use, and the presence of hypertension showed similar conclusions. Among those in the middle-aged and elderly general population without diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up.

Association between hypouricemia and reduced kidney function: a cross-sectional population-based study in Japan.

BACKGROUND: Hypouricemia, conventionally defined as a serum uric acid level of ≤2 mg/dl, is considered a biochemical disorder with no clinical significance. However, individuals with renal hypouricemia have a high risk of urolithiasis and exercise-induced acute kidney injury, both of which are risk factors for reduced kidney function. METHODS: To test the hypothesis that individuals with hypouricemia would be at a higher risk of reduced kidney function, we conducted a population-based cross-sectional study using data from the Specific Health Checkups and Guidance System in Japan. Logistic analysis was used to examine the relationship between hypouricemia and reduced kidney function, defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2). RESULTS: Among 90,710 men (mean age, 63.8 years) and 136,935 women (63.7 years), 193 (0.2%) and 540 (0.4%) were identified as having hypouricemia, respectively. The prevalence of hypouricemia decreased with age in women (p for trend <0.001), but not in men (p for trend = 0.24). Hypouricemia was associated with reduced kidney function in men (odds ratio, 1.83; 95% confidence interval, 1.23-2.74), but not in women (0.61; 0.43-0.86), relative to the reference category (i.e., serum uric acid levels of 4.1-5.0 mg/dl) after adjusting for age, drinking, smoking, diabetes, hypertension, hypercholesterolemia, obesity, and history of renal failure. Sensitivity analyses stratified by diabetic status yielded similar results. CONCLUSIONS: This study is the first to provide evidence that hypouricemia is associated with reduced kidney function in men. Further research will be needed to determine the long-term prognosis of individuals with hypouricemia.

Blood Pressure, Proteinuria, and Renal Function Decline: Associations in a Large Community-Based Population.

BACKGROUND: Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. METHODS: We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. RESULTS: After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. CONCLUSIONS: This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.

Impact of the expression of thymidylate synthase and dihydropyrimidine dehydrogenase genes on survival in stage II/III gastric cancer.

BACKGROUND: The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the cornerstone of gastrointestinal cancer treatment, depends upon the expression of enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT). We analyzed the expression of these genes in patients enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) and their possible roles as biomarkers for treatment outcomes. METHODS: Formalin-fixed, paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3 %) patients. TS, DPD, TP, and OPRT expression was measured by RT-PCR in manually microdissected tumor specimens and normalized to the reference gene, ß-actin. The expression level of each gene was categorized as low or high using cutoffs at the 33.3rd, 50th, or 66.7th percentiles. RESULTS: The hazard ratio (HR) for overall survival (OS) after S-1 treatment versus surgery alone was significantly lower in high (>66.7th percentile; HR = 0.370; 95 % CI 0.221-0.619) compared to low (<66.7th percentile; HR = 0.757; 95 % CI 0.563-1.018) TS expression groups (P = 0.015). Similarly, the HR for OS after S-1 therapy versus surgery alone was significantly lower in high (>33.3rd percentile; HR = 0.520, 95 % CI 0.376-0.720) compared to low (<33.3rd percentile; HR = 0.848, 95 % CI 0.563-1.276) DPD expression groups (P = 0.065). There was no interaction between TP or OPRT expression and OS. CONCLUSIONS: This large biomarker study showed that high TS and DPD gene expression in tumors was associated with enhanced benefit from postoperative adjuvant S-1 treatment in gastric cancer. There was no interaction between TP and OPRT expression and S-1 treatment.

Comparison of predictive value for first cardiovascular event between Japanese GFR equation and coefficient-modified CKD-EPI equation.

BACKGROUND: The most superior GFR-estimating equation from the viewpoint of cardiovascular disease (CVD) prediction remains unclear. Thus, we performed cross-sectional comparison between two GFR-estimating equations (Japanese GFR equation and coefficient-modified CKD-EPI equation) and CVD incidence using Japanese nationwide "specific health checkup" data. METHODS: We recruited Japanese residents (241,159 individuals; mean 63 years; male, 38.6 %) who had not experienced CVD event (cardiac disease or stroke, or both). We calculated estimated GFR using two equations, and compared their predictive value for first symptomatic CVD event within 1 year. RESULTS: Of all subjects, the mean GFR estimated by the Japanese GFR equation (JPN-eGFR) modified for Japanese was 75.83 ± 16.18 mL/min/1.73 m(2), and that by the coefficient-modified CKD-EPI equation (mCKDEPI-eGFR) was 76.39 ± 9.61 mL/min/1.73 m(2). Area under the receiver operating characteristics curves (95 % confidence intervals) for predicting CVD event by mCKDEPI-eGFR vs. JPN-eGFR were 0.596 (0.589-0.603) vs. 0.562 (0.554-0.569). Using mCKDEPI-eGFR, the crude odds ratio (OR) for CVD incident in the 4th quartile group was far more than double (OR 2.46, 95 % CI 2.29-2.66) that in the 1st quartile group. Using JPN-eGFR, the crude OR in the 4th quartile group was less than double (OR 1.61, 95 % CI 1.51-1.73) that in the 1st quartile group. However, such superior predictive value of mCKDEPI-eGFR disappeared after adjustment for confounding factors (age, gender, BMI, presence of proteinuria, hypertension, diabetes, dyslipidemia and current smoking). CONCLUSION: GFR estimated by the coefficient-modified CKD-EPI equation was more closely related to CVD incidence than that estimated by the Japanese GFR equation. However, it is possible that low mCKDEPI-eGFR also reflects some cardiovascular risk(s) other than kidney dysfunction.

Significance of estimated glomerular filtration rate in predicting brain or heart attacks in obese and non-obese populations.

BACKGROUND: The Japanese Specific Health Checkup mainly focuses on metabolic syndrome for preventing cardiovascular events. Subjects are stratified by measuring waist circumference, body mass index, blood pressure, triglycerides, and fasting plasma glucose. However, estimated glomerular filtration rate (eGFR) is not considered essential. METHODS: A longitudinal cohort study assessed the association of eGFR with new-onset brain or heart attacks in a large Japanese nationwide Specific Health Checkup database. A total of 109,349 Japanese subjects (mean age 63.2 years, 39.5 % men) were examined for the events 2 years later. The odds ratios were calculated for new events in the total and subgroup populations divided by BMI < or ≥25 kg/m(2), obese and non-obese, respectively. RESULTS: Obese subjects were more often male and had proteinuria (dipstick test ≥1+), lower eGFR, and higher systolic and diastolic BP, fasting plasma glucose, hemoglobin A1c, and triglycerides (TG). Rates of new-onset brain or heart attacks were 3.1 and 4.0 % in the groups of non-obese and obese subjects, respectively. In the total population, eGFR as well as higher BMI (≥25 kg/m(2)), higher BP (high-normal hypertension or greater), higher TG (≥150 mg/dl), and proteinuria were significant risk factors for developing brain or heart attacks. The eGFR was significant in non-obese subjects, but not in the obese. CONCLUSION: As the ultimate aim of 'Specific Health Checkup' is to prevent cardiovascular events, our study suggests that eGFR should be evaluated in non-obese subjects.

Association between combined lifestyle factors and non-restorative sleep in Japan: a cross-sectional study based on a Japanese health database.

BACKGROUND: Although lifestyle factors such as cigarette smoking, excessive drinking, obesity, low or no exercise, and unhealthy dietary habits have each been associated with inadequate sleep, little is known about their combined effect. The aim of this study was to quantify the overall impact of lifestyle-related factors on non-restorative sleep in the general Japanese population. METHODS AND FINDINGS: A cross-sectional study of 243,767 participants (men, 39.8%) was performed using the Specific Health Check and Guidance System in Japan. A healthy lifestyle score was calculated by adding up the number of low-risk lifestyle factors for each participant. Low risk was defined as (1) not smoking, (2) body mass index<25 kg/m², (3) moderate or less alcohol consumption, (4) regular exercise, and (5) better eating patterns. Logistic regression analysis was used to examine the relationship between the score and the prevalence of non-restorative sleep, which was determined from questionnaire responses. Among 97,062 men (mean age, 63.9 years) and 146,705 women (mean age, 63.7 years), 18,678 (19.2%) and 38,539 (26.3%) reported non-restorative sleep, respectively. The prevalence of non-restorative sleep decreased with age for both sexes. Compared to participants with a healthy lifestyle score of 5 (most healthy), those with a score of 0 (least healthy) had a higher prevalence of non-restorative sleep (odds ratio, 1.59 [95% confidence interval, 1.29-1.97] for men and 2.88 [1.74-4.76] for women), independently of hypertension, hypercholesterolemia, diabetes, and chronic kidney disease. The main limitation of the study was the cross-sectional design, which limited causal inferences for the identified associations. CONCLUSIONS: A combination of several unhealthy lifestyle factors was associated with non-restorative sleep among the general Japanese population. Further studies are needed to establish whether general lifestyle modification improves restorative sleep.

New-onset hypertension and risk for chronic kidney disease in the Japanese general population.

OBJECTIVES: Our aims were to assess the progression rate of normotension and prehypertension to hypertension in Japan, and the effect of the new-onset hypertension on chronic kidney disease (CKD). METHODS: This was a nationwide study of 45 378 Japanese aged 40-74 years (mean age 60 years, 37% men) without hypertension or cardiovascular disease at baseline. At baseline and 3-year follow-up, blood pressure (BP) and kidney function were assessed. CKD was defined as an estimated glomerular filtration rate (eGFR) below 60 ml/min per 1.73 m² or the presence of proteinuria (≥1+ by a dipstick). RESULTS: At 3-year follow-up, the incidence rates of hypertension among participants with optimal BP (<120/80 mmHg, n = 18,724), normal BP (120-129/80-84 mmHg, n = 15,017) and high-normal BP (130-139/85-89 mmHg, n = 11,637) were 8, 23, and 39% in men, and 6, 20, and 37% in women, respectively. Among those without CKD at baseline (n = 42,625), 2142 participants (5%) had developed CKD during follow-up. Irrespective of the baseline BP classifications, participants with new-onset hypertension had a higher risk for proteinuria [odds ratio (95% confidence interval) 1.7 (1.3-2.3) in men and 1.6 (1.2-2.2) in women], but not for eGFR below 60 ml/min per 1.73 m², compared with those who maintained optimal BP during follow-up. Men who remained in the high-normal BP range during follow-up showed higher risk for proteinuria [odds ratio (95% confidence interval) 1.6 (1.1-2.3)], but not for eGFR below 60 ml/min per 1.73 m². CONCLUSIONS: This nationwide longitudinal study suggests that, over 3 years of follow-up, women and men with new-onset hypertension and men with high-normal BP were at higher risk of newly developing proteinuria.

Association of the triglycerides to high-density lipoprotein cholesterol ratio with the risk of chronic kidney disease: analysis in a large Japanese population.

OBJECTIVES: To investigate the relationship between triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) and chronic kidney disease (CKD). METHODS: We used data from 216,007 Japanese adults who participated in a nationwide health checkup program. Men (n = 88,516) and women (n = 127,491) were grouped into quartiles based on their TG/HDL-C levels (<1.26, 1.26-1.98, 1.99-3.18, and >3.18 in men; <0.96, 0.96-1.44, 1.45-2.22, and >2.22 in women). We cross-sectionally assessed the association of TG/HDL-C levels with CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) (low eGFR) and/or proteinuria (defined as urinary protein ≥ 1+ on dipstick testing)], low eGFR, and proteinuria. RESULTS: The prevalence of CKD, low eGFR, and proteinuria increased significantly with elevating quartiles of TG/HDL-C in both genders (all P for trend <0.001). Participants in the highest quartile of TG/HDL-C had a significantly greater risk of CKD than those in the lowest quartile after adjustment for the relevant confounding factors (odds ratio: 1.57, 95% confidence interval: 1.49-1.65 in men; 1.41, 1.34-1.48 in women, respectively). Furthermore, there were significant associations with low eGFR and proteinuria. In stratified analysis, the risk of CKD increased linearly with greater TG/HDL-C levels in participants with and without hypertension, diabetes, and obesity. Moreover, higher TG/HDL-C levels were relevant for CKD, especially in participants with hypertension and diabetes (P for interaction <0.001, respectively). CONCLUSIONS: An elevated TG/HDL-C is associated with the risk of CKD in the Japanese population.

An association between serum γ-glutamyltransferase and proteinuria in drinkers and non-drinkers: a Japanese nationwide cross-sectional survey.

BACKGROUND: The association between alcohol consumption and chronic kidney disease (CKD), characterized by reduced glomerular filtration rate and proteinuria, is controversial. Recent studies suggest that serum γ-glutamyltransferase (GGT) level, a conventional marker of excessive alcohol consumption, predicts the CKD incidence. Little information is available on the difference in the clinical impact of alcohol consumption and GGT on proteinuria. METHODS: The present cross-sectional survey included 332,296 Japanese people aged ≥40 years in 2008. To examine the associations of GGT and alcohol consumption with proteinuria, 134,600 men and 197,696 women were classified into 20 categories based on GGT quartiles and alcohol consumption categories, and their prevalence rate ratios (PRR) of proteinuria defined as ≥1+ of dipstick urinary protein were calculated after adjusting for clinically relevant factors. RESULTS: Prevalence of proteinuria was 7.5 and 3.7 % in men and women, respectively. In both gender an association between alcohol consumption and proteinuria was in a J-shaped fashion with the lowest PRR of mild drinkers with ≤19 g/day of ethanol consumption, whereas an association between serum GGT level and proteinuria was linear. Compared with rare drinkers in the lowest GGT quartile, the subjects in higher GGT quartiles had a higher probability of proteinuria, irrespective of alcohol consumption. An optimal cutoff level of serum GGT was 43.6 and 23.2 IU/L in men and women, respectively. CONCLUSIONS: The subjects with higher serum GGT level had a higher probability of proteinuria, regardless of alcohol consumption, suggesting that GGT has a clinically greater impact on CKD than alcohol consumption.

U-shaped association between body mass index and proteinuria in a large Japanese general population sample.

BACKGROUND: There is little data on the association between body mass index (BMI) and proteinuria. METHODS: This was a cross-sectional cohort study assessing the association between BMI and proteinuria in a large Japanese population. Using a nationwide health check-up database of 212,251 Japanese aged >20 years with no pre-existing cardiovascular diseases (185,183 men, median age 66 years; 127,068 women, median age 65 years), we examined the association between BMI and proteinuria (≥ 1+ on dipstick). RESULTS: Subjects were divided into 11 subgroups by BMI grading in 1 kg/m(2) intervals from 18.5-27.5 kg/m(2). A BMI of approximately 22 ± 0.5 kg/m(2) was considered optimal for Japanese; therefore, this subgroup was set as a reference when logistic analysis was applied. Age, waist circumference, height, weight, smoking and drinking habits, use of medications such as antihypertensive, antidiabetic, or antihyperlipidemic, as well as proteinuria, estimated glomerular filtration rate (eGFR), chemistry data, and blood pressure levels were significantly different between subgroups in both genders. The odds ratio for proteinuria showed a U-shape in men and women, even after adjustment for significant covariates such as age, waist circumference, systolic blood pressure, eGFR, fasting plasma glucose, triglyceride, low-density lipoprotein, antihypertensive use, antidiabetic use, antihyperlipidemic use, and lifestyle factors (smoking and drinking). Gender differences were also prominent--a BMI <20.4 kg/m(2) was significantly associated with proteinuria in men compared to a BMI <18.4 kg/m(2) in women. On the other hand, a BMI ≥ 25.5 kg/m(2) was also significantly associated with proteinuria in men compared to a BMI ≥ 22.5 kg/m(2) in women. CONCLUSIONS: We found that BMI levels were associated with proteinuria in a U-shaped manner and showed marked gender differences. Health guidance should not only focus on higher BMI subjects, but also on thin subjects, in terms of the prevention of chronic kidney disease.

Confidence interval of intrinsic optimum temperature estimated using thermodynamic SSI model.

The intrinsic optimum temperature for the development of ectotherms is one of the most important factors not only for their physiological processes but also for ecological and evolutional processes. The Sharpe-Schoolfield-Ikemoto (SSI) model succeeded in defining the temperature that can thermodynamically meet the condition that at a particular temperature the probability of an active enzyme reaching its maximum activity is realized. Previously, an algorithm was developed by Ikemoto (Tropical malaria does not mean hot environments. Journal of Medical Entomology, 45, 963-969) to estimate model parameters, but that program was computationally very time consuming. Now, investigators can use the SSI model more easily because a full automatic computer program was designed by Shi et al. (A modified program for estimating the parameters of the SSI model. Environmental Entomology, 40, 462-469). However, the statistical significance of the point estimate of the intrinsic optimum temperature for each ectotherm has not yet been determined. Here, we provided a new method for calculating the confidence interval of the estimated intrinsic optimum temperature by modifying the approximate bootstrap confidence intervals method. For this purpose, it was necessary to develop a new program for a faster estimation of the parameters in the SSI model, which we have also done.

Prediction-based threshold for medication alert.

This study presents a prediction-based approach to determine thresholds for a medication alert in a computerized physician order entry. Traditional static thresholds can sometimes lead to physician's alert fatigue or overlook potentially excessive medication even if the doses are belowthe configured threshold. To address this problem, we applied a random forest algorithm to develop a prediction model for medication doses, and applied a boxplot to determine the thresholds based on the prediction results. An evaluation of the eight drugs most frequently causing alerts in our hospital showed that the performances of the prediction were high, except for two drugs. It was also found that using the thresholds based on the predictions would reduce the alerts to a half of those when using the static thresholds. Notably, some cases were detected only by the prediction thresholds. The significance of the thresholds should be discussed in terms of the trade-offs between gains and losses; however, our approach, which relies on physicians' collective experiences, has practical advantages.