Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.

A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903.

BACKGROUND: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. PATIENTS AND METHODS: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. RESULTS: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). CONCLUSIONS: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

Daytime Dynamo Electrodynamics With Spiral Currents Driven by Strong Winds Revealed by Vapor Trails and Sounding Rocket Probes.

We investigate the forces and atmosphere-ionosphere coupling that create atmospheric dynamo currents using two rockets launched nearly simultaneously on 4 July 2013 from Wallops Island (USA), during daytime Sq conditions with ΔH of -30 nT. One rocket released a vapor trail observed from an airplane which showed peak velocities of >160 m/s near 108 km and turbulence coincident with strong unstable shear. Electric and magnetic fields and plasma density were measured on a second rocket. The current density peaked near 110 km exhibiting a spiral pattern with altitude that mirrored that of the winds, suggesting the dynamo is driven by tidal forcing. Such stratified currents are obscured in integrated ground measurements. Large electric fields produced a current opposite to that driven by the wind, believed created to minimize the current divergence. Using the observations, we solve the dynamo equation versus altitude, providing a new perspective on the complex nature of the atmospheric dynamo.

A self-reported measurement scale on a potential component of competency in the healthcare staff engaged in the prevention and control of non-communicable disease in Fiji.

BACKGROUND: According to the World Health Organization, an estimated 80% or more deaths in Pacific island countries, including Fiji, were related to non-communicable diseases (NCDs). Although competency-based approaches have been effective for developing healthcare workers' capabilities, there are only a few reports on competency scales of healthcare workers for NCD prevention. We aimed to develop a self-reported measurement scale on a potential component of competency in the healthcare staff engaged in the prevention and control of NCDs in Fiji. METHODS: There were 378 Ministry of Health and Medical Services staff members working on NCD prevention and control in Fiji included in this study, which was a cross-sectional survey of social factors, working situation factors, and competency. Exploratory factor analysis was conducted to assess potential competency components, whereas Cronbach's α coefficient and analysis of variance were used to assess the validity and reliability of the scale items, respectively. Multivariate regression analyses were conducted to analyze the respondents' factor scores relative to social status and work situations. RESULTS: The factor analysis revealed 16 items that identified competency in four work types: 1) work management, 2) monitoring and evaluation, 3) community partnership, and 4) community diagnosis. The monitoring and evaluation roles were related to ethnic background, community partnership was related to religion, and community diagnosis was related to academic qualifications. CONCLUSIONS: Based on the results, we developed a competency scale for the four work types. This scale can help healthcare workers engage in better management of residents with NCDs in Fiji.

Similar Outcomes of Kidney Transplantations Using Organs From Donors After Cardiac Death and Donors After Brain Death.

BACKGROUND: To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. METHODS: At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). RESULTS: Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. CONCLUSIONS: Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD.

Early Outcomes of Living-Donor Kidney Transplantation With Immunosuppression Therapy Induction With Tacrolimus Extended-Release: A Comparison With Cyclosporine.

BACKGROUND: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. METHODS: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. RESULTS: The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. DISCUSSION: Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. CONCLUSION: TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.

An Examination of Pregnancy Cases After Kidney Transplantation: Single-Center Experience.

INTRODUCTION: The number of young women who wish to become pregnant opting for kidney transplants is increasing, as becoming pregnant under hemodialysis or peritoneal dialysis is associated with many risks. However, there have been reports indicating that these patients are subject to a higher risk of miscarriage compared to women with normal renal function. We examine and report cases of patients that experienced pregnancy after undergoing kidney transplantation at our hospital. SUBJECTS AND METHOD: Of the kidney transplantation cases that were performed at our hospital between 1985 and 2016, there were 7 cases of pregnancy. The serum creatinine levels, urine protein findings, etc, of these 7 cases were examined during the pre-pregnancy, pregnancy, childbirth, and postpartum periods. RESULTS: All 7 cases were able to give birth. There were two cases of transient postpartum hypertension. There were no cases of obvious pregnancy toxemia or fetal growth retardation. Two of the cases resulted in the failure of the transplanted kidneys. DISCUSSION: According to previous studies on pregnancy and childbirth after kidney transplantation, the presence of high blood pressure and proteinuria as well as the renal function at the time of pregnancy is closely associated with postpartum renal function. Urine protein was detected prior to pregnancy in both cases and resulted in the failure of the transplanted kidneys. The influence of immunosuppressants on the mother and fetus is also an important consideration. CONCLUSION: We believe it is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female transplant recipients.

Origin of magnetic properties in carbon implanted ZnO nanowires.

Various synchrotron radiation-based spectroscopic and microscopic techniques are used to elucidate the room-temperature ferromagnetism of carbon-doped ZnO-nanowires (ZnO-C:NW) via a mild C+ ion implantation method. The photoluminescence and magnetic hysteresis loops reveal that the implantation of C reduces the number of intrinsic surface defects and increases the saturated magnetization of ZnO-NW. The interstitial implanted C ions constitute the majority of defects in ZnO-C:NW as confirmed by the X-ray absorption spectroscopic studies. The X-ray magnetic circular dichroism spectra of O and C K-edge respectively indicate there is a reduction in the number of unpaired/dangling O 2p bonds in the surface region of ZnO-C:NW and the C 2p-derived states of the implanted C ions strongly affect the net spin polarization in the surface and bulk regions of ZnO-C:NW. Furthermore, these findings corroborate well with the first-principles calculations of C-implanted ZnO in surface and bulk regions, which highlight the stability of implanted C for the suppression and enhancement of the ferromagnetism of the ZnO-C:NW in the surface region and bulk phase, respectively.

Subjective Well-Being Is Associated with Food Behavior and Demographic Factors in Chronically Ill Older Japanese People Living Alone.

OBJECTIVES: This study aimed to examine the relationships among subjective well-being, food and health behaviors, socioeconomic factors, and geography in chronically ill older Japanese adults living alone. DESIGN: The design was a cross-sectional, multilevel survey. A questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people living alone based on their proximity to a supermarket. Study recruitment was conducted with municipal assistance. MEASUREMENTS: To assess subjective well-being and food and health behaviors of respondents with disease, a logistic regression analysis was performed using stepwise variable analyses, adjusted for respondent age, socioeconomic status, and proximity to a supermarket. The dependent variable was good or poor subjective well-being. RESULTS: In total, 2,165 older people (744 men, 1,421 women) completed the questionnaire (63.5% response rate). Data from 737 men and 1,414 women were used in this study. Among people with a chronic disease, individuals with good subjective well-being had significantly higher rates than those with poor subjective well-being for satisfaction with meal quality and chewing ability, food diversity, food intake frequency, perception of shopping ease, having someone to help with food shopping, eating home-produced vegetables, preparing breakfast themselves, eating with other people, and high alcohol consumption. A stepwise logistic analysis showed that the factors strongly related to poor subjective well-being were shopping difficulty (men: odds ratio [OR] = 3.19, 95% confidence interval [CI], 1.94-5.23; P < 0.0001; women: OR = 2.20, 95% CI, 1.54-3.14; P < 0.0001), not having someone to help with food shopping (women: OR = 1.41, 95% CI, 1.01-1.97; P = 0.043), not preparing breakfast (women: OR = 2.36, 95% CI, 1.40-3.98; P = 0.001), and eating together less often (women: OR = 1.99, 95% CI, 1.32-3.00; P = 0.002). CONCLUSION: Subjective well-being of people with chronic diseases is associated with food intake and food behavior. The factors that affect poor subjective well-being in chronically ill older Japanese people living alone include food accessibility and social communication.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Alcohol Energy Intake Is Related to Low Body Mass Index in Japanese Older Adults: Data from the 2010-2011 National Health and Nutrition Survey.

OBJECTIVE: The objective of this study was to identify lifestyle and nutritional factors associated with low BMI in Japanese older adults, with a focus on alcohol energy intake. DESIGN: Cross-sectional study. PARTICIPANTS: Data from 1,093 respondents (711 men and 382 women) to the National Health and Nutrition Survey aged 65 years and older were included in this study. MEASUREMENTS: Data were analyzed for associations between BMI and lifestyle, energy, and nutrient intake. Alcohol energy intake was calculated from total energy and participants were categorized into BMI quartiles. Energy-adjusted nutrient intakes were calculated as residuals from a regression model, with BMI as the independent variable and lifestyle factors and nutrient intake as dependent variables. Between-BMI quartile differences were assessed for each sex using multivariate logistic regression analysis. In addition, the nutrient intakes of men consuming more than 280 kcal and less than 280 kcal of alcohol energy per day were compared. RESULTS: Men and women in the lowest BMI quartile had lower total energy intake but higher alcohol energy intake than men in the other BMI quartiles. In multivariate logistic regression analysis, the lowest BMI quartile was associated with total energy (OR: 0.81, p = 0.0310) and alcohol energy intake (OR: 1.22, p = 0.0472) in men. In men, protein, carbohydrate, fat, calcium, iron, and vitamin intakes were less in those that consumed ≥ 280 kcal than in those that consumed < 280 kcal of alcohol per day. CONCLUSION: Our results demonstrate an association between alcohol energy intake and low BMI in older Japanese individuals.

Relationship between diet-related indicators and overweight and obesity in older adults in rural Japan.

OBJECTIVES: To identify the relationship between diet-related indicators and overweight and obesity in older adults in rural Japan. DESIGN: Cross-sectional survey. SETTING: Obira, Hokkaido, Japan. PARTICIPANTS: Local residents aged between 65 and 74 years, except for those with poor health, were included. INTERVENTION: A health- and diet-related questionnaire was applied to participants house-to-house by trained health professionals. MEASUREMENTS: The following indicators were examined: number of meals, number of balanced meals, food diversity, food group diversity, chewing ability, alcohol intake habit, smoking habit, instrumental activities of daily living scores, age, and residing alone or with family. RESULTS: Of 550 residents, 317 residents completely responded to the questionnaire. Of these, 41 were had low body mass index (BMI≤20) and were excluded. This resulted in a sample of 307 subjects comprising 117 men and 190 women; 37.6% and 46.8% of men and women were classified as obese (BMI≥25), respectively. Women with a normal BMI (20

"Eating Together" Is Associated with Food Behaviors and Demographic Factors of Older Japanese People Who Live Alone.

OBJECTIVE: This study aimed to examine the relationships between eating together and subjective health, frailty, food behaviors, food accessibility, food production, meal preparation, alcohol intake, socioeconomic factors and geography among older Japanese people who live alone. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people who lived alone based on their proximity to a supermarket. Recruitment for the study was conducted with municipal assistance. MEASUREMENTS: A logistic regression analysis was performed that adjusted for the respondent's age, socioeconomic status and proximity to a supermarket using stepwise variable analyses. The dependent variable was whether the respondent ate together more or less than once a month. RESULTS: In total, 2,196 older people (752 men and 1,444 women) completed the questionnaire (63.5% response rate). It was found that 47.1% of men and 23.9% of women ate together less than once a month. Those who ate together less than once a month had a significantly lower rate of subjective health, food diversity and food intake frequency than those who ate together more often. A stepwise logistic analysis showed that the factors most strongly related to eating together less than once a month were not having any food shopping assistance (men: OR = 3.06, women: OR = 2.71), not receiving any food from neighbors or relatives (men: OR = 1.74, women: OR = 1.82), daily alcohol intake (women: OR = 1.83), frailty (men: OR = 0.48) and income (men: OR = 2.16, women: OR = 1.32). CONCLUSION: Eating together is associated with subjective health and food intake. Factors that affect how often older Japanese people who live alone eat together include food accessibility, daily alcohol intake, frailty and a low income.

Association between Satisfaction with State of Health and Meals, Physical Condition and Food Diversity, Health Behavior, and Perceptions of Shopping Difficulty among Older People Living Alone in Japan.

OBJECTIVE: This study aimed to examine perceptions of shopping difficulty, and the relationships with satisfaction with state of health and meals, physical condition, food diversity and health behavior in older people living alone in Japan. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by mail and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select the sample of older people living alone, by proximity to a supermarket. In total, 2,346 older people (827 men and 1,519 women) completed the questionnaire. MEASUREMENTS: The dependent variable was whether shopping was easy or difficult. A logistic regression analysis was performed, adjusting for age, socioeconomic status and proximity of residence to a supermarket using stepwise variable analyses. RESULTS: The response rate was 67.8%. Overall, 14.5% of men and 21.7% of women considered shopping difficult. The stepwise logistic analysis showed that the factors most strongly related to shopping difficulty were a subjective feeling of poor health (men: OR = 3.01, women: OR = 2.16) and lack of satisfaction with meals (men: OR = 2.82, women: OR = 3.69). Other related physical condition and dietary factors were requiring nursing care (men: OR = 3.69, women: OR = 1.54), a high level of frailty, measured using the frailty index score (women: OR = 0.36) and low food diversity score (men: OR = 1.84, women: OR = 1.36). CONCLUSION: The study found that older people's assessment of their shopping difficulty was related to satisfaction aspects, including a subjective feeling of poor health, and lack of satisfaction with meals, as well as physical condition. These have a greater influence on shopping difficulty than income in both sexes, and proximity to a supermarket in women.

IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.

BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.

Incidence and prevalence of childhood-onset Type 1 diabetes in Japan: the T1D study.

AIMS: A majority of children with Type 1 diabetes in Japan are registered with the government-subsidized Specified Pediatric Chronic Disease Treatment Research Projects (SPCDTRP). In this study, the incidence and prevalence of childhood-onset (< 15 years) Type 1 diabetes in Japan were estimated by drawing on SPCDTRP data. METHODS: Data available for 2005-2012 from the SPCDTRP and Statistics Bureau, Ministry of Internal Affairs and Communications were used to estimate the incidence of Type 1 diabetes for 2005-2010, adjusted to cover those registered within 3 years of disease onset and stratified by sex, age at onset and period of onset. RESULTS: The incidence of Type 1 diabetes for 2005-2010 was 2.25/100,000 persons [95% confidence intervals (95% CI), 2.14-2.36] (boys: 1.91, 95% CI, 1.83-1.98; girls: 2.52, 95% CI, 2.34-2.69), with that for the age brackets 0-4, 5-9 and 10-14 years being 1.48 (95% CI, 1.29-1.66), 2.27 (95% CI, 2.08-2.47) and 3.00 (95% CI, 2.74-3.25), respectively. The onset of disease was shown to peak at age 13 among boys (3.28, 95% CI, 3.02-3.55) and at age 10 among girls (3.28, 95% CI, 3.02-3.55). The peak periods of disease onset were April/May and December. The number of children aged < 15 years with Type 1 diabetes for 2005-2012 was estimated to be 2326 (95% CI, 2202-2450) with the prevalence estimated as 13.53/100,000 persons (95% CI, 12.63-14.43). CONCLUSIONS: Study findings demonstrated no increase in the incidence of Type 1 diabetes, although suggesting, in agreement with earlier reports, that the onset of disease peaks in adolescence with a female predominance. In addition, the incidence of childhood-onset diabetes exhibited an annual bimodal pattern in this study.

Food Accessibility and Perceptions of Shopping Difficulty among Elderly People Living Alone in Japan.

OBJECTIVES: This aim of this study was to describe the association between shopping difficulty and food accessibility for elderly people living alone in Japan. DESIGN: A cross-sectoral, multilevel survey was designed to measure shopping difficulty from a food accessibility perspective. The questionnaire was distributed by mail. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select the sample: it identified the proximity of elderly people living alone to a supermarket. In total, 2,028 elderly people (725 men and 1,303 women) responded to the questionnaire. MEASUREMENTS: The binary dependent variables were shopping is easy/shopping is difficult. A logistic regression analysis adjusting for age and area of residence and using stepwise variable analyses was performed. RESULTS: The response rate was 58.6%. Overall, 14.6% of elderly men and 21.7% of elderly women consider shopping difficult. The stepwise logistic analysis showed that the food accessibility factors strongly related to shopping difficulty are infrequent car use (women: OR = 6.97), walking difficulties (men: OR = 2.81, women: OR = 3.48), poor eyesight (men: OR = 2.26, women: OR = 1.75), not cooking lunch by oneself (men: OR = 1.63, women: OR = 1.72), not having anyone to help with food shopping (women: OR = 1.45) and living over 1 km away from a supermarket (men: OR = 2.30, women: OR = 2.97). CONCLUSION: The study concludes that elderly people's assessment of shopping difficulty is related to their food accessibility. Important food accessibility aspects include car or motorbike ownership, walking continuously for 1 km, poor eyesight, and having cooking skills and having someone to help with shopping. These physical activity restrictions have a greater influence on shopping difficulty than do either income or proximity to a supermarket.

Postoperative Compensatory Changes and Blood Flow Parameter of the Preserved Kidney in Elderly Living Related Donors Evaluated by Doppler Ultrasonography.

INTRODUCTION: Elderly kidney donors have recently become more common in living related kidney transplantation in Japan. Therefore, it is important to evaluate whether kidney function in elderly donors after nephrectomy is preserved over long periods of time. Doppler ultrasonography measurement is practical for donors after nephrectomy because it involves simple and noninvasive examinations. Doppler ultrasonography can detect compensatory hypertrophy and blood flow parameters, namely resistive index (RI) and pulsatility index (PI), of the preserved kidney in living donors. PATIENTS AND METHODS: Our study included 58 donors, divided into 2 groups according to age; the elderly donor group was comprised of those 65 years old or older. We measured length, width, and short diameter of the preserved kidney using Doppler ultrasonography, and calculated kidney volume. RESULTS: The elderly group was comprised of 13 patients. In this group, the median preserved kidney volume was 145.0 cm(3) (101.8-193.5) before nephrectomy, and 127.6 cm(3) (99.0-183.4) and 145.5 cm(3) (141.3-148.6) at 1 and 12 months after nephrectomy, respectively. We did not observe significant compensatory hypertrophy in the preserved kidneys of elderly donors postoperatively. Both the mean PI and RI values of elderly donors increased progressively after nephrectomy. No compensatory hypertrophy occurred in the preserved kidneys of elderly donors, although the PI and RI did increase in these donors. CONCLUSION: Our results indicate that nephrectomy caused nephrosclerosis in the preserved kidneys of elderly donors and that prevention of hypertension may be important after nephrectomy in elderly donors.