MsABCG1, ATP-Binding Cassette G transporter from Medicago Sativa, improves drought tolerance in transgenic Nicotiana Tabacum.

Drought has a devastating impact, presenting a formidable challenge to agricultural productivity and global food security. Among the numerous ABC transporter proteins found in plants, the ABCG transporters play a crucial role in plant responses to abiotic stress. In Medicago sativa, the function of ABCG transporters remains elusive. Here, we report that MsABCG1, a WBC-type transporter highly conserved in legumes, is critical for the response to drought in alfalfa. MsABCG1 is localized on the plasma membrane, with the highest expression observed in roots under normal conditions, and its expression is induced by drought, NaCl and ABA signalling. In transgenic tobacco, overexpression of MsABCG1 enhanced drought tolerance, evidenced by increased osmotic regulatory substances and reduced lipid peroxidation. Additionally, drought stress resulted in reduced ABA accumulation in tobacco overexpressing MsABCG1, demonstrating that overexpression of MsABCG1 enhanced drought tolerance was not via an ABA-dependent pathway. Furthermore, transgenic tobacco exhibited increased stomatal density and reduced stomatal aperture under drought stress, indicating that MsABCG1 has the potential to participate in stomatal regulation during drought stress. In summary, these findings suggest that MsABCG1 significantly enhances drought tolerance in plants and provides a foundation for developing efficient drought-resistance strategies in crops.

Bioinspired cytomembrane coating besieges tumor for blocking metabolite transportation.

The metabolite transport inhibition of tumor cells holds promise to achieve anti-tumor efficacy. Herein, we presented an innovative strategy to hinder the delivery of metabolites through the in-situ besieging tumor cells with polyphenolic polymers that strongly adhere to the cytomembrane of tumor cells. Simultaneously, these polymers underwent self-crosslinking under the induction of tumor oxidative stress microenvironment to form an adhesive coating on the surface of the tumor cells. This polyphenol coating effectively obstructed glucose uptake, reducing metabolic products such as lactic acid, glutathione, and adenosine triphosphate, while also causing reactive oxygen species to accumulate in the tumor cells. The investigation of various tumor models, including 2D cells, 3D multicellular tumor spheroids, and xenograft tumors, demonstrated that the polyphenolic polymers effectively inhibited the growth of tumor cells by blocking key metabolite transport processes. Moreover, this highly adhesive coating could bind tumor cells to suppress their metastasis and invasion. This work identified polyphenolic polymers as a promising anticancer candidate with a mechanism by impeding the mass transport of tumor cells.

Prevalence, severity, and risk factors of cancer-related fatigue among working cancer survivors: a systematic review and meta-analysis.

PURPOSE: The aim of this study is to evaluate the prevalence, severity, and risk factors of cancer-related fatigue among currently working cancer survivors. METHODS: We searched the PubMed, Embase, Scopus, CINAHL, Cochrane Library, and ICHUSHI databases. The risk of bias was evaluated independently using the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS). A meta-analysis was conducted to determine the prevalence, severity, and related factors associated with cancer-related fatigue among currently working cancer survivors. RESULTS: Our meta-analysis included 18 studies and revealed that 42.2% of currently working cancer survivors experience cancer-related fatigue. The fatigue severity in this group was significantly higher than that in workers without cancer (absolute standardized mean difference (SMD) = 0.67), but lower than that in cancer survivors who had previously worked and were not currently working (absolute SMD = 0.72). Distress was identified as a potential risk factor for cancer-related fatigue in working cancer survivors (partial correlation coefficient = 0.38). CONCLUSIONS: The high prevalence of cancer-related fatigue among employed cancer survivors underscores the need for targeted workplace interventions and fatigue management strategies. While the severity of fatigue is less than that seen in non-working survivors, the comparison with the general working population highlights a significant health disparity. The association between distress and fatigue suggests the necessity for a holistic approach to fatigue management that considers both physical and mental factors in working cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Our findings highlight the critical need for healthcare professionals and employers to monitor fatigue levels among working cancer survivors and offer appropriate support.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study.

OBJECTIVE: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. MATERIALS AND METHODS: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated. RESULTS: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). CONCLUSION: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

Renal Dysfunction after Rectal Cancer Surgery: A Long-term Observational Study.

Objectives: Despite the high incidence of urinary dysfunction (UD) after rectal surgery, it remains questionable whether UD causes future chronic kidney disease (CKD). This study aimed to clarify the long-term trends in renal function and risk factors for future CKD after rectal resection. Methods: For comparison, patients who underwent rectal resection (n = 129) and colectomy (n = 127) between 2006 and 2017 were identified. The estimated glomerular filtration rate (eGFR) ratio was calculated as the ratio to the baseline. "eGFR ratio < 0.75 at 3-year" was adopted as a surrogate indicator of future CKD. Results: eGFR ratio significantly decreased in the rectal cohort compared with the colon cohort at 1.5 years (0.9 vs. 0.95, p = 0.008) and at 3 years (0.85 vs. 0.94, p < 0.001). Although the preoperative prevalence of CKD was lower in the rectal than the colon cohort (13.9% vs. 23.6%, p = 0.055), it was similar at 3 years (29.5% vs. 30.7%). In multivariate analysis, females, and cT4 were independent risk factors for future CKD, but UD itself was not. Conclusions: Postoperative eGFR significantly decreased after rectal cancer surgery compared to colectomy. The prevalence of CKD more than doubled at 3 years after rectal resection. The female sex and cT4 tumor, instead of the UD, were independent risk factors for future CKD.

Risk and population attributable fraction of stroke subtypes in Japan.

BACKGROUND: Associations of major risk factors for stroke with total and each type of stroke as well as subtypes of ischemic stroke and their population attributable fractions had not been examined comprehensively. METHODS: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n=14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥ 25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (< 40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fraction (PAF) was estimated using the hazard ratios and the prevalence of risk factors among cases. RESULTS: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic and large-artery occlusive strokes were 36.7 and 44.5% and 61.5%, respectively. CONCLUSION: Although there are differences according to the subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Long-term variability and change trend of systolic blood pressure and risk of type 2 diabetes mellitus in middle-aged Japanese individuals: findings of the Aichi Workers' Cohort Study.

Studies have reported that short-term blood pressure (BP) variability (BPV) is associated with type 2 diabetes mellitus (T2DM) incidence, but the association with long-term BPV remains unclear. The present study investigated the associations of long-term BPV as well as the time trend of BP changes over time with the incidence of T2DM. This study followed a cohort of 3017 Japanese individuals (2446 male, 571 female) aged 36-65 years from 2007 through March 31, 2019. The root-mean-square error (RMSE) and the slope of systolic BP (SBP) change regressed on year were calculated individually using SBP values obtained from 2003 to baseline (2007). A multivariable Cox proportional hazard model was applied to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for tertiles of SBP RMSE and continuous SBP slopes adjusted for age, sex, smoking status, regular exercise, sodium intake, family history of diabetes, sleep disorder, body mass index (BMI), SBP, and fasting blood glucose (FBG) at baseline, and BMI slope from 2003 to 2007. The highest RMSE tertile compared to the lowest was associated with a significantly higher incidence of T2DM after adjusting for covariates (HR: 1.79, 95% CI: 1.15, 2.78). The slope was also significantly associated with T2DM incidence until baseline SBP and FBG were adjusted (HR: 1.03, 95% CI: 0.99, 1.07). In conclusion, long-term SBP variability was significantly associated with an increased incidence of T2DM independent of baseline age, sex, BMI, SBP, FBG, lifestyle factors and BMI slope from 2003 until baseline.

Recent findings on subjective well-being and physical, psychiatric, and social comorbidities in individuals with schizophrenia: A literature review.

AIM: Care for people with schizophrenia is shifting the locus from long-stay mental hospitals to nonspecialized community-based settings. Knowledge on the care is not a sole property of psychiatric specialists. Community healthcare workers who do not specialize in psychiatry are recommended to learn more about schizophrenia. This review aimed to summarize recent findings on subjective well-being and physical, psychiatric, and social comorbidities in individuals with schizophrenia. METHODS: A literature review was conducted. We retrieved findings from existing systematic reviews and meta-analyses as our preferred method. When data were not available, we referred to other types of studies. RESULTS: As per our review, individuals with schizophrenia demonstrated poor subjective well-being, happiness, and life satisfaction despite individual differences. Pharmacotherapy caused weight gain and constipation, whereas race and hospitalization might affect weight reduction. Individuals with schizophrenia demonstrated poor oral health, a high prevalence of noncommunicable diseases, and unique eating behaviors. Depression, sleep disorders, smoking, and alcohol and drug consumption were frequently found in the individuals. Research findings regarding problematic internet and smartphone use and stress perception were limited. Low health literacy and neglect of preventable behaviors were frequently seen in individuals with schizophrenia. They tended to be less educated, poor, unemployed, unmarried/unattached, and had poor social cognition, resulting in little social support and a small social network. CONCLUSION: Retrieving recent data, we confirmed that individuals with schizophrenia had poor subjective well-being and suffer from various physical, psychiatric, and social comorbidities.

Stoma creation is associated with a low incidence of midline incisional hernia after colorectal surgery: the "fighting over the fascia" theory concerning the incision and stoma hole.

PURPOSE: Parastomal hernia (PH) develops more frequently than incisional hernia (IH) after colorectal surgery with stoma. This study evaluated our hypothesis that inward traction of the fascia when closing a midline incision widens the stoma hole and increases the incidence of PH. METHODS: A total of 795 patients who underwent colorectal resection between 2006 and 2016 were retrospectively analyzed. The risk classification was constructed from IH risk factors extracted from the non-stoma group. Then, the classification was extrapolated to the stoma group for predicting midline IH and PH. RESULTS: The incidence of IH was 5.3% in the stoma group and 12.5% in the non-stoma group (p = 0.005). PH developed in 19.6% of 97 patients with permanent stoma. The risk classification was able to predict PH without a significant difference but was well balanced in patients with permanent stoma; however, it failed to predict IH in the stoma group. CONCLUSION: The risk classification constructed from the non-stoma group was useful for predicting not midline IH but PH, suggesting that the stoma site was the most vulnerable for herniation. The "fighting over the fascia" theory between the midline incision and stoma hole may explain the causal relationship between the midline IH and PH.

Comparison of laminoplasty and posterior fusion surgery for cervical ossification of posterior longitudinal ligament.

This prospective multicenter study, established by the Japanese Ministry of Health, Labour and Welfare and involving 27 institutions, aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL), in order to address the controversy surrounding the role of instrumented fusion in cases of posterior surgical decompression for OPLL. 478 patients were considered for participation in the study; from among them, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, there were no significant differences among the participants in terms of patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments. The overall risk of perioperative complications was found to be lower with LM (odds ratio [OR] 0.40, p = 0.006), and the rate of C5 palsy occurrence was significantly lower with LM (OR 0.11, p = 0.0002) than with PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p < 0.0001) in patients who had PF was significantly smaller than in those who had LM. However, multivariable logistic regression analysis showed no significant difference among the participants in JOA score, JOA recovery rate, or JOACMEQ improvement at two years. In contrast, OPLL progression was greater in the LM group than in the PF group (OR 2.73, p = 0.0002). Both LM and PF for cervical myelopathy due to OPLL had resulted in comparable postoperative outcomes at 2 years after surgery.

Impact of Body Mass Index on Obesity-Related Cancer and Cardiovascular Disease Mortality; The Japan Collaborative Cohort Study.

AIM: We aimed to examine the association of obesity-related cancer and cardiovascular disease (CVD) with body mass index (BMI) and the estimated population attributable fraction in lean Asians. METHODS: We studied 102,535 participants aged 40-79 years without histories of cancer or CVD at baseline between 1988 and 2009. The cause-specific hazard ratios (csHRs) of BMI categories (＜18.5, 18.5-20.9, 21.0-22.9 [reference], 23.0-24.9, 25.0-27.4, and ≥ 27.5 kg/m2) were estimated for each endpoint. The events considered were mortalities from obesity-related cancer (esophageal, colorectal, liver, pancreatic, kidney, female breast, and endometrial cancer) and those from CVD (coronary heart disease and stroke). Population attributable fractions (PAFs) were calculated for these endpoints. RESULTS: During a 19.2-year median follow-up, 2906 died from obesity-related cancer and 4532 died from CVD. The multivariable-adjusted csHRs (95% confidence interval) of higher BMI categories (25-27.4 and ≥ 27.5 kg/m2) for obesity-related cancer mortality were 0.93 (0.78, 1.10) and 1.18 (0.92, 1.50) in men and 1.25 (1.04, 1.50) and 1.48 (1.19, 1.84) in women, respectively. The corresponding csHRs for CVD mortality were 1.27 (1.10, 1.46) and 1.59 (1.30, 1.95) in men and 1.10 (0.95, 1.28) and 1.44 (1.21, 1.72) in women, respectively. The PAF of a BMI ≥ 25 kg/m2 for obesity-related cancer was -0.2% in men and 6.7% in women and that for CVD was 5.0% in men and 4.5% in women. CONCLUSION: A BMI ≥ 25 kg/m2 is associated with an increased risk of obesity-related cancer in women and CVD in both sexes.

Working cancer survivors' physical and mental characteristics compared to cancer-free workers in Japan: a nationwide general population-based study.

PURPOSE: This study compared working cancer survivors' self-rated health status (SRHS), physical functional capacity, depressive symptoms, and happiness to those of cancer-free workers. METHODS: A nationwide general population-based cross-sectional study on a sample of Japanese was conducted. Prevalence of deteriorated SRHS, restricted physical functional capacity, depressive symptoms, and perceived happiness were compared between working cancer survivors and cancer-free workers with multivariable logistic regression analysis adjusted for age and sociodemographic and health-related backgrounds. RESULTS: Of the 28,311 male and 26,068 female workers, 977 (3.5%) and 1267 (4.9%) were cancer survivors, respectively. Working cancer survivors reported deteriorated SRHS more frequently than cancer-free workers: 21.3% vs. 13.8%, multivariable-adjusted odds ratio (95% confidence interval), 1.64 (1.39-1.95) for men, 23.8% vs. 17.5%, 1.34 (1.16-1.54) for women. Restricted physical functional capacity was reported more frequently in working cancer survivors than cancer-free workers: 6.8% vs. 2.6%, 1.76 (1.34-2.32) for men, 4.9% vs. 2.0%, 2.06 (1.56-2.71) for women. No significant difference was found for depressive symptoms: 21.6% vs. 22.9% in men, 30.0% vs. 28.5% in women. Working cancer survivors felt happiness more frequently than cancer-free survivors in men (77.3% vs. 71.7%, 1.21 (1.01-1.45)) but not in women (76.1% vs. 74.9%). CONCLUSIONS: Working cancer survivors had worse SRHS and more restricted physical functional capacity than cancer-free workers. In men, working cancer survivors felt happiness more frequently than cancer-free workers. IMPLICATIONS FOR CANCER SURVIVORS: Continuous support to improve cancer survivors' SRHS and physical functional capacity would be necessary even while they are working.

Estimation of 10-Year Risk of Death from Coronary Heart Disease, Stroke, and Cardiovascular Disease in a Pooled Analysis of Japanese Cohorts: EPOCH-JAPAN.

AIMS: We aimed to develop and validate risk prediction models to estimate the absolute 10-year risk of death from coronary heart disease (CHD), stroke, and cardiovascular disease (CVD). METHODS: We evaluated a total of 44,869 individuals aged 40-79 years from eight Japanese prospective cohorts to derive coefficients of risk equations using cohort-stratified Cox proportional hazard regression models. Discrimination (C-index) of the equation was examined in each cohort and summarised using random-effect meta-analyses. Calibration of the equation was assessed using Hosmer-Lemeshow chi-squared statistic. RESULTS: Within a median follow-up of 12.7 years, we observed 765 deaths due to CVD (276 CHDs and 489 strokes). After backward selection, age, sex, current smoking, systolic blood pressure (SBP), proteinuria, prevalent diabetes mellitus, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDLC), interaction terms of age by SBP, and age by current smoking were retained as predictors for CHD. Sex was excluded in the stroke equation. We did not consider TC/HDLC as a risk factor for the stroke and CVD equations. The pooled C-indices for CHD, stroke, and CVD were 0.83, 0.80, and 0.81, respectively, and the corresponding p-values of the Hosmer-Lemeshow tests were 0.18, 0.003, and 0.25, respectively. CONCLUSIONS: Risk equations in the present study can adequately estimate the absolute 10-year risk of death from CHD, stroke, and CVD. Future work will evaluate the system as an education and risk communication tool for primary prevention of CHD and stroke.

Pelvic exenteration associated with future renal dysfunction.

PURPOSE: This study aimed to clarify the long-term change in the renal function after pelvic exenteration (PE) and to evaluate the risk factors for any future dysfunction. METHODS: This study comprised 40 patients. A greater than 25% decline in the estimated glomerular filtration rate (eGFR) at 3 years was defined as early renal function disorder (ERFD), possibly predicting future chronic kidney disease (CKD). RESULTS: In the entire cohort, the median eGFR decreased by 23% at 3 years, and CKD developed in 50%. The patients were divided into the ERFD (n = 16) and non-ERFD (n = 24) groups. In the ERFD group, the eGFR significantly decreased by 28% during the first 1.5 years and continued to decline after that, resulting in 81.3% of patients reaching CKD, whereas it was 4% and 37.5%, respectively, in the non-ERFD group. In a growth model analysis, late urinary tract complications (UTC) and small bowel obstruction were shown to be risk factors for ERFD. CONCLUSION: Although PE was associated with a high incidence of future CKD, ERFD could predict it. Close observation of the eGFR decline over 1.5 years might be beneficial to identify ERFD patients. High-risk patients with late UTC and small bowel obstruction should, therefore, be observed carefully.

Functional Analysis of the Phosphate Transporter Gene MtPT6 From Medicago truncatula.

Phosphorus is one of the essential macronutrients required by plant growth and development, but phosphate resources are finite and diminishing rapidly because of the huge need in global agriculture. In this study, 11 genes were found in the Phosphate Transporter 1 (PHT1) family of Medicago truncatula. Seven genes of the PHT1 family were available by qRT-PCR. Most of them were expressed in roots, and almost all genes were induced by low-phosphate stress in the nodule. The expression of MtPT6 was relatively high in nodules and induced by low-phosphate stress. The fusion expression of MtPT6 promoter-GUS gene in M. truncatula suggested that the expression of MtPT6 was induced in roots and nodules by phosphate starvation. In roots, MtPT6 was mainly expressed in vascular tissue and tips, and it was also expressed in cortex under low-phosphate stress; in nodules, it was mainly expressed in vascular bundles, cortical cells, and fixation zone cells. MtPT6 had a close relationship with other PHT1 family members according to amino acid alignment and phylogenetic analysis. Subcellular localization analysis in tobacco revealed that MtPT6 protein was localized to the plasma membrane. The heterologous expression of MtPT6 in Arabidopsis knockout mutants of pht1.1 and pht1.4 made seedlings more susceptible to arsenate treatment, and the phosphate concentrations in pht1.1 were higher in high phosphate condition by expressing MtPT6. We conclude that MtPT6 is a typical phosphate transporter gene and can promote phosphate acquisition efficiency of plants.

Smoking results in accumulation of ectopic fat in the liver.

OBJECTIVE: An association between smoking and nonalcoholic fatty liver disease has been reported. However, objective quantification of intrahepatic fat via magnetic resonance spectroscopy (MRS) in relation to smoking has rarely been performed in previous studies. Moreover, the possible pathways via which smoking could induce ectopic fat accumulation have not yet been addressed. The current study aimed to examine the association between smoking status and intrahepatic fat quantity and explore the possible mediating effects of triglycerides (TG) and adiponectin. SUBJECTS AND METHODS: Magnetic resonance imager (MRI) spectra were analyzed to quantify intrahepatic fat in 45 men who were on average 62.3 years of age. Smoking status and alcohol intake were self-reported. Accelerometers were used to record daily total physical activity. Fasting blood TG and adiponectin levels were measured enzymatically. Differences in mean intrahepatic fat values according to smoking status were assessed using analysis of covariance. RESULTS: A stepwise increase in mean intrahepatic fat was observed between never, former, and current smokers, respectively, independent of age, physical activity, alcohol intake, and body mass index (BMI) (P=0.005). Adjustment for TG and adiponectin significantly attenuated this association (P=0.074). CONCLUSION: Current smoking was significantly associated with increased intrahepatic fat, which may be a result of adipocyte dysfunction, manifested as high circulating TG concentrations and low adiponectin levels.

Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium.

OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN: Individual participant data meta-analysis. SETTING: Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Body Mass Index and Risks of Incident Ischemic Stroke Subtypes: The Japan Public Health Center-Based Prospective (JPHC) Study.

BACKGROUND: The association of body mass index (BMI) with risks of ischemic stroke subtypes have not been established. METHODS: Cumulative average BMI was calculated using self-reported body weight and height obtained from baseline (Cohort I in 1990, and Cohort II from 1993-1994) and 5- and 10-year questionnaire surveys of Japan Public Health Center-based prospective (JPHC) study. A total of 42,343 men and 46,413 women aged 40-69 years were followed-up for the incidence of lacunar, large-artery occlusive, and cardioembolic strokes. A sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and the 95% confidence intervals (CIs). RESULTS: During a median of 20.0 years of follow-up, we documented 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes in men and women, respectively. After adjustment for baseline age, updated smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus, cumulative average BMI was positively linearly associated with lacunar (trend P = 0.007), large-artery occlusive (trend P = 0.002), and cardioembolic (trend P < 0.001) strokes in men, and with lacunar (trend P < 0.001) and large-artery occlusive (trend P = 0.003) strokes in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for cumulative average BMI ≥30 kg/m2 compared to BMI 23-<25 kg/m2. CONCLUSION: Cumulative average BMI showed a positive linear effect on sub-distribution hazards of lacunar, large-artery occlusive, and cardioembolic strokes in both sexes, except for cardioembolic stroke in women.

A Point System for Predicting 10-Year Risk of Developing Type 2 Diabetes Mellitus in Japanese Men: Aichi Workers' Cohort Study.

BACKGROUND: Relatively little evidence exists for type 2 diabetes mellitus (T2DM) prediction models from long-term follow-up studies in East Asians. This study aims to develop a point-based prediction model for 10-year risk of developing T2DM in middle-aged Japanese men. METHODS: We followed 3,540 male participants of Aichi Workers' Cohort Study, who were aged 35-64 years and were free of diabetes in 2002, until March 31, 2015. Baseline age, body mass index (BMI), smoking status, alcohol consumption, regular exercise, medication for dyslipidemia, diabetes family history, and blood levels of triglycerides (TG), high density lipoprotein cholesterol (HDLC) and fasting blood glucose (FBG) were examined using Cox proportional hazard model. Variables significantly associated with T2DM in univariable models were simultaneously entered in a multivariable model for determination of the final model using backward variable selection. Performance of an existing T2DM model when applied to the current dataset was compared to that obtained in the present study's model. RESULTS: During the median follow-up of 12.2 years, 342 incident T2DM cases were documented. The prediction system using points assigned to age, BMI, smoking status, diabetes family history, and TG and FBG showed reasonable discrimination (c-index: 0.77) and goodness-of-fit (Hosmer-Lemeshow test, P = 0.22). The present model outperformed the previous one in the present subjects. CONCLUSION: The point system, once validated in the other populations, could be applied to middle-aged Japanese male workers to identify those at high risk of developing T2DM. In addition, further investigation is also required to examine whether the use of this system will reduce incidence.

Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

Seborrhoeic keratosis (SK) is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in SK tissues (n = 50), and explore whether the production of APP is related to the onset of SK and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-ß42) were more highly expressed in SK than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. ß-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in SK tissues (p<0.05). APP expression correlated positively with age in epidermis (p<0.05), but not in dermis. These findings suggest that overexpression of APP may promote the onset of SK and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of SK and skin ageing.