Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy : a multicenter, investigator‑blinded, randomized, parallel group controlled trial (PACI Study) : protocol for a randomized controlled trial

Background: Atopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis. Methods: This study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N = 650) 7–13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen’s egg allergy at the age of 28 weeks. Discussion: This is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

BackgroundThe usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.Methods and ResultsWe measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.ConclusionsIn patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

FMD, PWV, and Cardiovascular Events

Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

Repetition of Prediabetes Enhances the Risk of Developing Diabetes

We attempted to clarify the severity of the risk of diabetes mellitus (DM) in the individuals who repeatedly fulfill the criteria for prediabetes in both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The subjects were 2347 individuals who underwent annual health checkup at our hospital. They were classified as normal glucose tolerance or prediabetes as their yearly status of glucose tolerance for three years; furthermore, the individuals classified as prediabetes were subclassified into 3 groups. Among them, we focused the individuals who fulfilled the criteria for prediabetes in both FPG and HbA1c, and this group was named as PD3. Similarly, all subjects were categorized into 4 groups by the frequency of the status of PD3 during three years. Moreover, all subjects were categorized into 8 patterns when PD3 status was positive. Then, we surveyed the development of diabetes for 5 years, and the incidence rates (IRs) and the age- and sex-adjusted odds ratios (ORs) were obtained. A total of 188 subjects developed diabetes. The individuals in the group of PD3 showed the highest IR of DM (33.6%). The values of ORs were 11.5, 20.0, and 63.5 when the frequencies of PD3 were one, two, and three, respectively. In the group whose frequency of PD3 was two, the individuals who had repeated the status of PD3 twice then moved to the status other than PD3 showed smaller risk of DM than the others in the same group. In conclusion, individuals who fulfill the criteria for prediabetes in both FPG and HbA1c were at a high risk of developing DM, and the risk was enhanced by repeating this status. On the other hand, changing the status from PD3 to others might reduce the risk of DM

Association of overtime work hours with various stress responses in 59,021 Japanese workers: Retrospective cross-sectional study.

This study aims to clarify the relationships between length of overtime work and various stress responses using large-scale cross-sectional data of Japanese workers. This study's participants are 59,021 Japanese workers in 117 companies. Data was collected by self-reporting questionnaire. The Brief Job Stress Questionnaire was used to measure stress responses on six scales (i.e. "lack of vigor", "irritability", "fatigue", "anxiety", "depression", and "somatic responses"). Length of overtime work hours were classified as 0-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, and >80 hours/month. Multiple linear regression analyses were used to examine the association of stress responses with overtime while adjusting all possible confounders. In result, workers with longer overtime showed significantly higher "irritability", "fatigue", "anxiety", "depression", and "somatic responses" for both genders (p-for-trend <0.001), however, length of overtime was negatively associated with "lack of vigor" among men (p-for-trend <0.001). Men with 61-80 hours of overtime showed high fatigue with high vigor at the same time. Length of overtime was linearly associated with various stress responses, except for "lack of vigor". Length of overtime shows linear associations with various psychosomatic stress responses. However, "lack of vigor" was not consistently associated with overtime. Male workers with 61-80 hours of monthly overtime were more likely to feel vigorous than workers with shorter overtime. However, potential longterm effects of such extreme overtime should not be underestimated and must be paid attention to

Smoking Exposure Is Associated with Serum Vitamin D Deficiency in Children: Evidence from the Japan Environment and Children’s Study

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health

Perceived neighborhood environment and walking for specific purposes among elderly Japanese

Background: Recent research has revealed the importance of neighborhood environment as a determinant of physical activity. However, evidence among elderly adults is limited. This study examined the association between perceived neighborhood environment and walking for specific purposes among Japanese elderly adults. Methods: This population-based, cross-sectional study enrolled 1921 participants (age: 65–74 years, men: 51.9%). Neighborhood environment (International Physical Activity Questionnaire Environmental Module) and walking for specific purposes (ie, transportation or recreation) were assessed by self-report. Multilevel logistic regression analyses with individuals at level 1 and neighborhoods at level 2 were conducted to examine the association between environment and walking, after adjustment for potential confounders. Results: Access to exercise facilities, social environment, and aesthetics were associated with total neighborhood walking. Odds ratios (95% CI) were 1.23 (1.00–1.51), 1.39 (1.14–1.71), and 1.48 (1.21–1.81), respectively. Regarding walking for specific purposes, social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Environmental correlates differed by specific types of walking and by sex. Transportation walking significantly correlated with a greater variety of environmental attributes. Sex differences were observed, especially for transportation walking. Bicycle lanes, crime safety, traffic safety, aesthetics, and household motor vehicles were significant correlates among men, while access to shops, access to exercise facilities, and social environment were important among women. Conclusions: Specific environment–walking associations differed by walking purpose and sex among elderly adults. Social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Improving these environmental features might be effective in promoting physical activity among elderly Japanese