Enhancing exercise tolerance in interstitial lung disease with high-flow nasal cannula oxygen therapy: A randomized crossover trial.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is characterized by dyspnoea on exertion and exercise-induced hypoxaemia. High-flow nasal cannula (HFNC) therapy reduces the respiratory workload through higher gas flow and oxygen supplementation, which may affect exercise tolerance. This study aimed to examine the effects of oxygen and gas flow rates through HFNC therapy on exercise tolerance in ILD patients. METHODS: We conducted three-treatment crossover study. All ILD patients performed the exercises on room air (ROOM AIR setting: flow, 0 L/min; fraction of inspired oxygen [FiO2], 0.21), HFNC (FLOW setting: flow 40 L/min, FiO2 0.21), and HFNC with oxygen supplementation (FLOW + OXYGEN setting: flow 40 L/min, FiO2 0.6). The primary endpoint was the endurance time, measured using constant-load cycle ergometry exercise testing at a peak work rate of 80%. RESULTS: Twenty-five participants (10 men, 71.2 ± 6.7 years) were enrolled. The increase in exercise duration between the ROOM AIR and FLOW was 46.3 s (95% CI, -6.1 to 98.7; p = 0.083), and the FLOW and FLOW + OXYGEN was 91.5 s (39.1-143.9; p < 0.001). The percutaneous oxygen saturation (SpO2) at rest was significantly higher with the FLOW + OXYGEN setting than with the ROOM AIR and FLOW settings, and the difference persisted during exercise. At equivalent time points during exercise, the SpO2 with the FLOW setting was significantly higher than that with the ROOM AIR setting. CONCLUSION: Oxygen supplementation in HFNC therapy improved exercise tolerance and SpO2. We found that gas flow alone did not improve exercise tolerance, but improved SpO2 during exercise.

[Sub-staff training program for community residents to provide community-based care services at day-care facilities].

Objectives　As the birthrate declines and the population ages, increase in the number of older adults certified as requiring long-term care and shortage of care staff are important issues to be considered. This study developed a sub-staff training program that trains community residents as sub-staff (paid auxiliary staff who possess knowledge and skills in care prevention and confidentiality) to provide care for enhancing independence of older adults with the support of staff in day-care facilities. The study also examined the program's feasibility and key factors, through the introduction of practical examples and surveys, for implementation in care prevention projects of local governments.Methods　The four-month training program included lectures on care prevention and provided job training to ensure participants understood the goals and contents of the care plan and learnt to provide care services with the assistance of facility staff. The training program was conducted at 14 facilities in Tokyo and Chiba from 2015 to 2017. The evaluation focused on the completion rate, change in understanding of care prevention and confidence regarding activities at the facility and in the community, participation in community activities after program completion, the psychological impact on care service recipients, and the perception of workload reduction by the facility staff.Results　A total of 96 out of 104 participants completed the training program (completion rate of 92.3%). The survey results showed that participants' confidence in activities at the facilities and understanding of care prevention increased significantly; 65.3% participated in new community activities after program completion, including activities at the facilities. The results of the survey of care service recipients showed that negative psychological effects did not increase among those who received care services from the participants compared to those who did not receive care from participants. Among the facility staff, 85.7% indicated that their workload had reduced after the community residents' participation in care services.Conclusion　The training program improved participants' confidence in care-related activities and their understanding of care prevention. More than half of them engaged in new community activities afterwards. Participants' provision of care services had a less negative impact on the service recipients and led to a reduction in workload for the facility staff. These results suggest high feasibility of the training program for care prevention projects.

Time spent walking and disability-free survival in older Japanese: The Ohsaki Cohort 2006 Study.

The extent to which long disability-free survival (DFS) time can be extended according to the amount of time spent walking has not been investigated. The aim of this study was to examine the association between time spent walking per day and DFS time in older adults. We conducted a cohort study of 14 342 disability-free individuals (aged ≥ 65 years) living in Ohsaki City, Japan. The amount of time spent walking per day (<0.5 h, 0.5-1 h, ≥1 h) by each individual in 2006 was assessed by a self-reported questionnaire. Data on 11-year incident functional disability were retrieved from the public Long-Term Care Insurance database. After estimating the multivariable-adjusted hazard ratios (HRs) of the composite outcome (incident functional disability or death), the multivariable-adjusted 50th percentile differences (50th PDs; difference in the period until the first 50% of the composite outcome occurred) were estimated according to time spent walking. Among 114 764 person-years, the composite outcome occurred in 7761 persons (67.6 per 1000 person-years). The HRs (95% confidence intervals) of the composite outcome were 1.00 (reference) for <0.5 h, 0.84 (0.79, 0.88) for 0.5-1 h, and 0.78 (0.74, 0.83) for ≥1 h (p-trend < 0.001). The 50th PDs (95% confidence intervals) of DFS time were 238 (155, 322) days longer for 0.5-1 h and 360 (265, 454) days longer for ≥1 h, in comparison with <0.5 h. The results suggest that longer time spent walking per day contributes to longer DFS time.

[Factors associated with participation in community activities after receiving long-term care preventive services].

Objectives　Since amending the long-term care insurance system to cover community-based services in 2015, community activities led by older residents have become increasingly important in Japan. It is necessary for local governments to effectively promote participation in community activities during long-term care prevention services. This study aimed to identify the factors associated with participation in community activities and the contents of intervention after long-term care prevention services in which interventions were conducted to promote older residents' participation in community activities.Methods　A secondary analysis of data collected in two classes of long-term care preventive services of a local government in Tokyo was conducted. This service provided not only interventions to improve physical function but also initiatives to promote participation in community activities after the service, such as learning and group-work activities. We analyzed participants' responses to self-administered questionnaires in 2016 and 2017; three months after the service started (T1) and six months after the service ended (T2). A total of 216 people (51 men and 165 women; age range: 65-95 years) responded to the questionnaires. Types of intervention, self-rated health, responses to the Kihon Checklist, and social capital, which was measured through items such as "Interaction with neighbors (SC1)," "Participation in groups other than preventive activity (SC2)," "Strength of trust for neighbors (SC3)," and "Mutual trust with neighbors (SC4)," were assessed at T1. Engaging in community activities was assessed to determine whether they participated in the self-motivating group for preventive activity at T2. Logistic regression analyses were conducted to examine the factors associated with participation in community activities by adjusting for each variable.Results　Totally, 113 respondents participated in community activities (participation rate=52.3%), and 103 did not participate (47.7%). Univariate logistic regression analyses revealed that types of intervention was significantly associated with participation in community activities (OR: 0.31, 95% CI: 0.15-0.63, P=0.001). Multivariate logistic regression models adjusted for all independent variables also indicated that types of intervention was significantly associated with participation in community activities (OR: 0.29, 95% CI: 0.14-0.62, P=0.001).Conclusion　The results showed that approximately 50% of the participants were involved in community activities because participation in such activities was promoted in long-term care preventive services. Types of intervention was a significant factor associated with participation in community activities. These findings highlight the importance of program contents in community activities during preventive services.

[Association between issues in activities and psychosocial health status in the social positions of older residents' community-based activities: a cross-sectional study].

Objectives　When local governments and community nurses provide support for community-based activities led by older residents, it is imperative to reduce the burden of participants in leadership positions. This study aimed to identify the issues associated with the activities by social position, such as leadership, support, and regular participation, to discuss effective support for community-based activities and to examine the association between social position, relating issues, and psychosocial health.Methods　Participants in community-based activities were recruited by the local government in Tokyo, Japan. Overall, 2,367 people from 155 activity groups from 40 municipalities responded. Social positions in the groups were defined as leaders who manage activities; supporters who support leaders; and regular members who do not have any specific role. The participants chose the issues of community-based activities from 10 items. Psychosocial health was measured by the WHO-5 well-being index (WHO-5) and Lubben social network scale-6 (LSNS-6). The relationship between recognition of issues and social positions were examined by the chi-square test. Interaction effects of social positions and issues (with or without) on the WHO-5 and LSNS-6 were investigated using a two-way analysis of covariance.Results　The final sample comprised 2,096 respondents: 174 leaders, 296 supporters, and 1,626 regular members. There was a significant association between recognition of social positions and issues in the groups: respondents who reported no issues in the activities comprised 8.6% of the leaders, 27.7% of the supporters, and 53.6% of the regular members (P<0.001). There was a large difference in recognition between roles for issues related to group management, such as the lack of management members. There was no significant interaction between these issues and social positions in either WHO-5 or LSNS-6 (P=0.729, P=0.171, respectively). The main effect of the social positions was significant in both analyses (P<0.001). The leaders and supporters showed significantly higher WHO-5 and LSNS-6 scores than regular members.Conclusion　The issues that the participants reported differed by social positions in activities. It may be effective to provide support according to the difficulty of sharing issues within the group. Regardless of whether or not the participants report issues, leaders and supporters had improved psychosocial health than regular members. The study concludes that organizational position in community-based activities may offer health benefits for older adults.

Prevalence of childhood wheeze and modified DNA methylation at 7 years of age according to maternal folate levels during pregnancy in the Hokkaido Study.

BACKGROUND: A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate-modified DNA methylation is related to asthma. Methods Participants in the current study were 6651 mother-child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case-control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies. Results The median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]); however, no changes were observed at 1, 4, and 7 years of age. In a case-control study, no association of maternal folate levels with DNA methylation was observed. Conclusion Our results suggest that maternal folate did not affect persistent wheezing in school-aged children, or DNA methylation of gasdermin B, orosomucoid-like 3, and Ikaros family zinc finger 3 at 7 years of age.

Complete genomic sequence of a novel phytopathogenic Burkholderia phage isolated from fallen leaf compost.

In contrast to most Burkholderia species, which affect humans or animals, Burkholderia glumae is a bacterial pathogen of plants that causes panicle blight disease in rice seedlings, resulting in serious damage to rice cultivation. Attempts to combat this disease would benefit from research involving a phage known to attack this type of bacterium. Some Burkholderia phages have been isolated from soil or bacterial species in the order Burkholderiales, but so far there has been no report of a complete genome nucleotide sequence of a phage of B. glumae. In this study, a novel phage, FLC5, of the phytopathogen B. glumae was isolated from leaf compost, and its complete genome nucleotide sequence was determined. The genome consists of a 32,090-bp circular DNA element and exhibits a phylogenetic relationship to members of the genus Peduovirus, with closest similarity to B. multivorans phage KS14. In addition to B. glumae, FLC5 was also able to lyse B. plantarii, a pathogen causing rice bacterial damping-off disease. This is the first report of isolation of a P2-like phage from phytopathogenic Burkholderia, determination of its complete genomic sequence, and the finding of its potential to infect two Burkholderia species: B. glumae and B. plantarii.

Predicting incidence of long-term care insurance certification in Japan with the Kihon Checklist for frailty screening tool: analysis of local government survey data.

BACKGROUND: Predicting incidence of long-term care insurance (LTCI) certification in the short term is of increasing importance in Japan. The present study examined whether the Kihon Checklist (KCL) can be used to predict incidence of LTCI certification (care level 1 or higher) in the short term among older Japanese persons. METHODS: In 2015, the local government in Tokyo, Japan, distributed the KCL to all individuals older than 65 years who had not been certified as having a disability or who had already been certified as requiring support level 1-2 according to LTCI system. We also collected LTCI certification data within the 3 months after collecting the KCL data. The data of 17,785 respondents were analyzed. First, we selected KCL items strongly associated with incidence of LTCI certification, using stepwise forward-selection multiple logistic regression. Second, we conducted receiver operating characteristic (ROC) analyses for three conditions (1: Selected KCL items, 2: The main 20 KCL items (nos. 1-20), 3: All 25 KCL items). Third, we estimated specificity and sensitivity for each condition. RESULTS: During a 3-month follow-up, 81 (0.5%) individuals required new LTCI certification. Eight KCL items were selected by multiple logistic regression as predictive of certification. The area under the ROC curve in the three conditions was 0.92-0.93, and specificity and sensitivity for all conditions were greater than 80%. CONCLUSIONS: Three KCL conditions predicted short-term incidence of LTCI certification. This suggests that KCL items may be used to screen for the risk of incident LTCI certification.

Mediating Factors Between Parental Socioeconomic Status and Small for Gestational Age in Infants: Results from the Hokkaido Study on Environment and Children's Health.

OBJECTIVES: Previous studies indicated a significant association between small for gestational age (SGA) in infants and their parents' socioeconomic status (SES). Thus, this study aimed to examine if parental factors, such as maternal smoking, and the pre-pregnancy body mass index (BMI) could mediate the associations between parental SES and SGA. METHODS: The participants of this study were pregnant women who enrolled in an ongoing birth cohort study, the Hokkaido study, during the first trimester of their pregnancies. A total of 14,593 live singleton births were included in the statistical analysis, of which 1011 (6.9%) were SGA. Two structural equation models were employed to evaluate the associations between parental SES, parental characteristics, and SGA. RESULTS: The effect of low SES on SGA was directly mediated by maternal pre-pregnancy BMI, smoking during the third trimester, and alcohol consumption during the first trimester in the first model, which was based the assumption of independent associations between mediating factors. In the second model, which additionally considered the mediating factors from the first model, smoking during pregnancy mediated decline in parental SES, consequently increased SGA. Moreover, an increase in pregnancy smoking status increased the prevalence of lower maternal pre-pregnancy BMI and its effect on SGA. CONCLUSIONS FOR PRACTICE: In this study, we observed the independent mediating effect of maternal pre-pregnancy BMI, smoking, and alcohol consumption during pregnancy on low SES and, consequently, SGA, with the additional mediating pathway of SES to smoking to low BMI on SGA.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

[Effective support based on length of participation for community-based activities led by older residents].

Objectives　Community-based activities led by older residents are important in preventing long-term care and enhancing social participation among older persons in Japan. Local governments and community nurses are required to support these activities. However, there is no knowledge about the issues of residents who participate in community-based activities, which is essential for the effective support of community-based activities. We aimed to examine the association between the length of participation and recognized issues among community-based activities.Methods　Through the local governments in Tokyo, we recruited participants from community-based activity groups; 2,367 people from 155 activity groups from 40 municipalities responded. The presence or absence of 10 items of recognized issues, such as lack of management members and lack of teachers, were examined. The number of years of participation in the activity was divided into four groups: "less than 1 year," "more than 1 year and less than 2 years," "more than 2 years and less than 4 years," and "more than 4 years." Logistic regression analysis was conducted to examine the association between the length of participation and recognized issues.Results　The number of analyzed respondents was 2,194 (14.5% were male and the average age was 76.9 years). Compared to "less than 1 year" group, the "more than 2 years and less than 4 year" group recognized "aging of group" (OR=1.92), "lack of management members" (OR=1.61), and "health condition of participants" (OR=1.47) as issues. In the "more than 4 years" group, "aging of group" (OR=3.24), "lack of management members" (OR=2.63), "lack of participants" (OR=2.12), "health condition of participants" (OR=1.95), "mannerism of activities" (OR=1.62), and "lack of place" (OR=1.48) were recognized as issues.Conclusion　Issues recognized by participants in community-based activities differed depending on the number of years they had been participating in the activity. This suggests that it is necessary to provide appropriate support taking the length of participation into account. For example, the issue of the "health condition of participants" was recognized by participants who had been participating in the activity for approximately two years. Consequently, "lack of participants" may have occurred in participants who have been participating in the activity for four years. Therefore, promoting the health management of participants from the early phase of community-based activity would be effective in preventing dropout.

Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children's Health.

BACKGROUND: Low red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan. METHODS: In total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression. RESULTS: Blood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4-21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74-1.32), 0.63 (95% CI, 0.30-1.33), and 4.10 (95% CI, 0.96-17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects. CONCLUSIONS: We were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.

Identification of a novel mechanism of action of bovine IgG antibodies specific for Staphylococcus aureus.

Staphylococcus aureus is a major pathogen that causes subclinical mastitis associated with huge economic losses to the dairy industry. A few vaccines for bovine mastitis are available, and they are expected to induce the production of S. aureus-specific antibodies that prevent bacterial adherence to host cells or promote opsonization by phagocytes. However, the efficacy of such vaccines are still under debate; therefore, further research focusing on improving the current vaccines by seeking additional mechanisms of action is required to reduce economic losses due to mastitis in the dairy industry. Here, we generated S. aureus-specific bovine IgG antibodies (anti-S. aureus) that directly inhibited bacterial growth in vitro. Inhibition depended on specificity for anti-S. aureus, not the interaction between Protein A and the fragment crystallizable region of the IgG antibodies or bacterial agglutination. An in vitro culture study using S. aureus strain JE2 and its deletion mutant JE2ΔSrtA, which lacks the gene encoding sortase A, revealed that the effect of anti-S. aureus was sortase-A-independent. Sortase A is involved in the synthesis of cell-wall-associated proteins. Thus, other surface molecules, such as membrane proteins, cell surface polysaccharides, or both, may trigger the inhibition of bacterial growth by anti-S. aureus. Together, our findings contribute insights into developing new strategies to further improve the available mastitis vaccine by designing a novel antigen on the surface of S. aureus to induce inhibitory signals that prevent bacterial growth.

Atmospheric-pressure plasma irradiation can disrupt tobacco mosaic virus particles and RNAs to inactivate their infectivity.

Low-temperature atmospheric-pressure air plasma is a source of charged and neutral gas species. In this study, N-carrying tobacco plants were inoculated with plasma irradiated and non-irradiated tobacco mosaic virus (TMV) solution, resulting in necrotic local lesions on non-irradiated, but not on irradiated, TMV-inoculated leaves. Virus particles were disrupted by plasma irradiation in an exposure-dependent manner, but the viral coat protein subunit was not. TMV RNA was also fragmented in a time-dependent manner. These results indicate that plasma irradiation of TMV can collapse viral particles to the subunit level, degrading TMV RNA and thereby leading to a loss of infectivity.

Prevalence and Risk of Birth Defects Observed in a Prospective Cohort Study: The Hokkaido Study on Environment and Children's Health.

BACKGROUND: Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation. METHODS: Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation. RESULTS: Prevalence of all birth defects was 18.9/1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term. CONCLUSIONS: Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects.

The Hokkaido Birth Cohort Study on Environment and Children's Health: cohort profile-updated 2017.

The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata and analysis of the microtubule assembly in the presence of taxol.

Taxol was originally isolated from the yew Taxus brevifolia. Because taxol inhibits the depolymerization of microtubules, the presence of a self-resistance mechanism in Taxus spp. was hypothesized. The cloning of the cDNA for alpha and beta tubulins from Taxus cuspidata and those from the human embryonic kidney cell line HEK293T revealed that the (26)Asp, (359)Arg, and (361)Leu residues in the human beta tubulin, which are important for taxol binding, were replaced with Glu, Trp, and Met in the beta tubulin of T. cuspidata, respectively. The microtubule assembly of the recombinant alpha and beta tubulins was monitored turbidimetrically, and the results clearly demonstrated that the microtubule from T. cuspidata is less sensitive to taxol than that from HEK293T cells. The Taxus microtubule composed of the wild-type alpha tubulin and the beta tubulin with the E26D mutation restored the sensitivity to taxol. We thus postulated that the mutation identified in the beta tubulin of T. cuspidata plays a role in the self-resistance of this species against taxol.

Three-year trajectories of social networks, face-to-face interactions, and non-face-to-face interactions among community-dwelling older adults in Japan during the COVID-19 pandemic: Otassha study.

OBJECTIVES: To investigate the trajectories of social networks and interactions among older Japanese individuals during the COVID-19 pandemic. STUDY DESIGN: We used data from a cohort of community-dwelling older individuals from the Otassha study's 2019-2022 survey. Participants comprised 606 older individuals who participated in the 2019 survey and were followed up at least once. MAIN OUTCOME MEASURES: Social networks were assessed using the Lubben Social Network Scale-6 (LSNS-6), whereas social interactions were assessed by the frequency of face-to-face or non-face-to-face contact with non-resident family members and friends. Trajectories of the LSNS-6 and face-to-face and non-face-to-face interactions were identified using group-based semiparametric mixture modeling. The trajectories of change in the LSNS-6 from 2019 were also identified. The factors associated with the changes in trajectory patterns were examined using logistic regression analysis. RESULTS: Three LSNS-6 trajectories were identified, with slightly decreasing patterns over time. Specifically, face-to-face interactions tended to decrease over time, whereas non-face-to-face interactions exhibited almost no change. The reduction in LSNS-6 in the decreased pattern failed to recover to its pre-pandemic level. The group of participants with the decreased pattern had a significantly higher proportion of people participating in group activities [odds ratio (95 % confidence interval): 2.27 (1.12-4.59)] and performing calisthenics twice a week than the group with the maintained pattern [2.08 (1.18-3.68)]. CONCLUSIONS: During the three years of the pandemic, no changes were observed in the social networks of community-dwelling older Japanese individuals.

Ay allele promotes azoxymethane-induced colorectal carcinogenesis by macrophage migration in hyperlipidemic/diabetic KK mice.

The incidence of colorectal cancer has been increasing and is associated with obesity and diabetes. We have found that type 2 diabetes model KK-Ay/TaJcl (KK-Ay) mice develop tumors within a short period after treatment with azoxymethane (AOM). However, factors that contribute to the promotion of carcinogenesis have not been clarified. Therefore, we looked at the genetic background of KK-Ay, including two genetic characteristics of KK/TaJcl (KK) mice and C57BL/6J-Ham-Ay/+ (Ay) mice, compared with other non-obese and non-diabetic mouse strains C57BL/6J and ICR, and induced colorectal premalignant lesions, aberrant crypt foci (ACF), and tumors using AOM (150 µg/mouse/week for 4 weeks and 200 µg/mouse/week for 6 weeks, respectively). The mice with a diabetes feature, KK-Ay and KK, developed significantly more ACF, 67 and 61 per mouse, respectively, whereas ICR, Ay, and C57BL/6J mice developed 42, 24, and 18 ACF/mouse, respectively, at 17 weeks of age. Serum insulin and triglyceride levels in KK-Ay and KK mice were quite high compared with other non-diabetic mouse strains. Interestingly, KK-Ay mice developed more colorectal tumors (2.7 ± 2.3 tumor/mouse) than KK mice (1.2 ± 1.1 tumor/mouse) at 25 weeks of age, in spite of similar diabetic conditions. The colon cancers that developed in both KK-Ay and KK mice showed similar activation of ß-catenin signaling. However, mRNA levels of inflammatory factors related to the activation of macrophages were significantly higher in colorectal cancer of KK-Ay mice than in KK. These data indicate that factors such as insulin resistance and dyslipidemia observed in obese and diabetic patients could be involved in susceptibility to colorectal carcinogenesis. In addition, increase of tumor-associated macrophages may play important roles in the stages of promotion of colorectal cancer.

Association between daily life walking speed and frailty measured by a smartphone application: a cross-sectional study.

OBJECTIVES: To assess whether frailty can be assessed using a smartphone and whether daily walking speed (DWS) is associated with frailty. DESIGN: Cross-sectional study. SETTING: Three prefectures (Kanagawa, Saitama and Tokyo) in Japan. PARTICIPANTS: The study enrolled 163 participants (65 in the robust group, 69 in the prefrailty group and 29 in the frailty group) by sending letters to house owners aged≥55 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants downloaded the DWS measurement application on their smartphones, which measured the daily walking (DW) parameters (DWS, step length and cadence) and the Kihon checklist for frailty assessment. The differences in the DW parameters between the robust, prefrailty and frailty groups were examined using one-way analysis of variance. We conducted logistic regression analysis for the Crude model (each DW parameter), model 1 (adjusted for the number of steps) and model 2 (model 1+age, sex and the number of chronic diseases). RESULTS: DWS was marginally significantly slower in the frailty group than in the prefrailty and robust group (robust 1.26 m/s vs prefrailty 1.25 m/s vs frailty 1.19 m/s, p=0.060). Step length was significantly smaller in the frailty group than in the robust group (robust 66.1 cm vs prefrailty 65.9 vs frailty 62.3 cm, p<0.01). Logistic regression analysis for the three models revealed that DWS was significantly associated with frailty. CONCLUSIONS: DWS measured using the smartphone application was associated with frailty. This was probably due to the shorter step length and body height seen in frail individuals.