Urolithin A suppresses NLRP3 inflammasome activation by inhibiting the generation of reactive oxygen species and prevents monosodium urate crystal-induced peritonitis.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1ß (IL-1ß) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1ß, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial reactive oxygen species.

Associations between the burdens of comorbid sleep problems, central sensitization, and headache-related disability in patients with migraine.

Objective: Sleep disturbances are common in migraine patients and affect quality of life. Central sensitization (CS) is likely to play a role in the increased severity and chronicity of migraine. We hypothesized that the number of comorbid sleep problems would affect headache-related disability through the effects of central sensitization (CS). Methods: We performed a cross-sectional study including 215 consecutive patients with migraine. Insomnia was defined as a Pittsburgh Sleep Quality Index (PSQI) global score greater than 5. Probable REM sleep behavior disorder (pRBD) was defined as an RBD screening score of 5 or greater. Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of 10 or higher. Suspected sleep apnea (SA) was defined as patients with snoring or sleep apnea witnessed 3 or more nights a week. CS was assessed by the Central Sensitization Inventory (CSI). Results: Restless legs syndrome, insomnia, EDS, SA and pRBD were observed in 25.6%, 71.6%, 34.4%, 10.2%, and 21.4%, respectively, of the patients. At least one sleep problem was present in 87.0% of the patients. According to the results of the multinomial logistic regression analysis with no sleep problems as a reference, after we corrected for adjustment factors, the Migraine Disability Assessment (MIDAS) score significantly increased when three or more comorbid sleep problems were present. According to our mediation analysis, an increased number of sleep problems had a direct effect on the MIDAS score after we adjusted for other variables, and the CSI score was indirectly involved in this association. Conclusion: The present study showed an association between migraine-related disability and the burden of multiple sleep problems, which was partially mediated by CS.

The COVID-19 pandemic affects pregnancy complications and delivery outcomes in Japan: a large-scale nationwide population-based longitudinal study.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes in Japan at the national level is unclear. This study aimed to assess the impact of the pandemic on pregnancy complications and delivery outcomes in Japan using nationwide population-based longitudinal data. Secondary data from the Japan Society of Obstetrics and Gynecology from 2016 to 2020 were analyzed. Obstetric information, pregnancy complications, and delivery information of pregnant women over 22 weeks of gestation were compared before and during the pandemic. The trends of hypertensive disorder of pregnancy, fetal growth restriction, and APGAR < 7 increased, whereas those of preterm birth and low birth weight decreased during the COVID-19 pandemic. Pregnancy complications and delivery outcomes have worsened during the COVID-19 pandemic in Japan. Social changes caused by unprecedented situations may have massively influenced pregnancy in several ways. Our findings suggest that even in mild lockdowns like those in Japan, the introduction of social fear during the pandemic might negatively impact pregnancy outcomes.

Clinical features and morphology of collagen fibrils in patients with vascular Ehlers-Danlos based on electron microscopy.

Background: Vascular-type Ehlers-Danlos syndrome (vEDS) is caused by collagen III deficit resulting from heterogeneous mutations in COL3A1, which occasionally causes sudden death due to arterial/visceral rupture. However, it is difficult to conduct basic research on the pathophysiology of vEDS. Moreover, the number of patients with vEDS is small, limiting the number of available samples. Furthermore, the symptoms of vEDS may vary among family members, even if they share the same mutation. Accordingly, many aspects of the pathology of vEDS remain unknown. Therefore, we investigated the structural abnormalities in collagen fibrils and endoplasmic reticulum (ER) stress in skin samples using electron microscopy as well as their relationship with clinical symptoms in 30 patients with vEDS (vEDS group) and 48 patients without vEDS (disease-negative control group). Methods: Differences between the two groups were evaluated in terms of the sizes of collagen fibrils using coefficient of variation (COV). Results: COV was found to be significantly higher in the vEDS group than in the disease-negative control group, indicating irregularity in the size of collagen fibrils. However, in the vEDS group, some patients had low COV and seldom experienced serious complications and ER stress. Conclusion: ER stress might affect collagen fibril-composing proteins. Moreover, as this stress varies among people based on environmental factors and aging, it may be the underlying cause of varying vEDS symptoms.

Anti-ß2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes.

Anti-ß2-glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-ß2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-ß2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-ß2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-ß2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-ß2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9-5.6], p < 0.001), FGR (2.7 [1.3-5.3], p < 0.01), and HDP (2.7 [1.4-5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-ß2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL.

The Factors Influencing Pregnant Women's Selection of Media Sources to Obtain Information on COVID-19 in Japan in 2021.

Pregnant women presumably gather information about the coronavirus disease 2019 (COVID-19) from various sources. However, it is difficult for pregnant women who are not medical professionals to source the appropriate information because of the infodemic related to the COVID-19 pandemic. Therefore, the objective of our study was to investigate how pregnant women gathered information about COVID-19 and COVID-19 vaccination. To address this issue, we conducted an online questionnaire survey between 5 October and 22 November 2021, which was approved by the Ethics Committee of Nihon University School of Medicine. We received 4962 responses after excluding 1179 insufficient answers. Our study found that age, occupation, and infection-risk anxiety influenced the selection of media for obtaining information. Pregnant women who were older, medical professionals, public servants, or educators tended to rely on specialized medical websites, whereas housewives tended to use mass media, social media, and sources with uncertain scientific evidence. Additionally, the number of weeks of gestation and the method of conception (natural or assisted reproductive conception) affected the selection of media. The accessibility of COVID-19 information for pregnant women was determined by their social background and pregnancy status. We need to continue making efforts to ensure that appropriate information is readily available to pregnant women and their families.

Comparison of Three Diagnostic Definitions of Metabolic Syndrome and Estimation of Its Prevalence in Mongolia.

We sought to estimate the prevalence of metabolic syndrome (MS) in the urban population of Mongolia and suggest a preferred definition. This cross-sectional study comprised 2076 representative samples, which were randomly selected to provide blood samples. MS was defined by the National Cholesterol Education Program's Adults Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). The Cohen's kappa coefficient (κ) was analyzed to determine the agreement between the individual MS components using the three definitions. The prevalence of MS in the 2076 samples was 19.4% by NCEP ATP III, 23.6% by IDF, and 25.4% by JIS criteria. For men, moderate agreement was found between the NCEP ATP III and waist circumference (WC) (κ = 0.42), and between the JIS and fasting blood glucose (FBG) (κ = 0.44) and triglycerides (TG) (κ = 0.46). For women, moderate agreement was found between the NCEP ATP III and high-density lipoprotein cholesterol (HDL-C) (κ = 0.43), and between the JIS and HDL-C (κ = 0.43). MS is highly prevalent in the Mongolian urban population. The JIS definition is recommended as the provisional definition.

Vascular endothelial growth factor isoforms are expressed in the uterus during estrous cycle of golden hamsters (Mesocricetus auratus).

We investigated VEGF expression in the uterus during the estrous cycle in the golden hamster (Mesocricetus auratus). Reverse transcription polymerase chain reaction of genes expressed in the uterus revealed the presence of at least three different VEGF isoforms (hamster VEGF188, VEGF164, and VEGF120). They were highly homologous to the respective mouse and human isoforms. Furthermore, VEGF164 and VEGF120 were predominantly expressed in the hamster uterus during the estrous cycle. In situ hybridization revealed that VEGF is expressed only in the luminal and glandular epithelium of the endometrium but not in the stromal cells or myometrium. The positive reaction of luminal and glandular epithelial cells on day 4 of the estrous cycle (day 1 = day of ovulation) was a little stronger than that of other days of the cycle. These findings suggest that VEGF molecules are secreted by endometrial epithelial cells and play an important role in the maintenance of blood vessels in the endometrial stroma. These results also suggest that uterine changes, such as edema, observed from day 4 to day 1 of the estrous cycle, are expected to occur primarily through the action of VEGF secreted by the uterine endometrial epithelium in preparation for subsequent embryo implantation.

Maternal heated tobacco product use during pregnancy and allergy in offspring.

BACKGROUND: Little is known about the association between maternal use of heated tobacco products (HTPs) during pregnancy and the onset of allergy among offspring. This study aimed to determine whether maternal HTP smoking is associated with allergy in their offspring and to evaluate the potential dose-response association. METHODS: In this web-based, cross-sectional survey conducted in July and August 2021 in Japan, we investigated 5688 pairs of postpartum women and infants (<3 years). Clinical diagnoses of infant asthma, rhinitis, conjunctivitis, or atopic dermatitis were reported. Using multilevel Poisson regression, we estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) of allergy in infants with HTP smoking categories cross-classified by pregnancy periods, and adjusted for potential covariates including maternal cigarette smoking and partner's smoking status. Non-smokers served as the reference group. RESULTS: In total, 2.4% women smoked HTPs during pregnancy. Allergy occurred in 7.8% of the infants. The prevalence of allergy increased among the offspring of current HTP smokers during pregnancy at 15.2% (PR = 1.98, 95% CI 1.28-3.05); this association was the most pronounced during the first trimester but attenuated before pregnancy and postpartum. Dose-response associations were observed, for example a one-unit increase in daily maternal HTP use during pregnancy was associated with a 5% increase in allergy onset. Sub-group analyses excluding cigarette smokers during pregnancy and sensitivity analyses using the International Study of Asthma and Allergies in Childhood questionnaire showed a similar pattern. CONCLUSIONS: Maternal HTP smoking during pregnancy is associated with allergy in the offspring.

Trends in Lifestyle-related Diseases and Their Risk Factors After the Fukushima Daiichi Nuclear Power Plant Accident: Results of the Comprehensive Health Check in the Fukushima Health Management Survey.

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011-2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011-2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008-2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011-2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

Association between the interval of worksite dental check-ups and dental and medical expenditures: a single-site, 12-year follow-up study in Japan.

OBJECTIVES: The purpose of this study was to identify the effective intervals of worksite dental check-ups to reduce cumulative dental expenditures (CDEs) and cumulative medical expenditures (CMEs), based on 12 years of follow-up dental check-ups. SETTING, DESIGN AND PARTICIPANTS: A longitudinal study was conducted between 2002 and 2014 fiscal years. A total of 2691 full-time employees (2099 males and 592 females) aged 20-59 years in a manufacturing company in Japan were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Based on the follow-up of 12-year dental check-ups, the interval of dental check-ups visits was classified into the following categories: 'Once per year' as the regular group, 'At least once per 2 years' as the subregular group and others as the irregular group. CDEs and CMEs per capita were examined by the three groups of dental check-ups interval after adjustment for sex, age, occupation and total CMEs at baseline. For sensitivity analysis, decayed teeth, missing teeth and Community Periodontal Index were added as adjustment factors. RESULTS: Compared with the irregular group, the pooled CDEs (including dental check-ups fee) per capita in the subregular group (OR 0.91, 95% CI 0.85 to 0.98) and regular group (OR 0.87, 95% CI 0.81 to 0.93) were significantly lower overall. The younger adults in the subregular group and younger-aged and middle-aged adults in the regular group had significantly lower CDEs. Sensitivity analysis confirmed these findings. CONCLUSIONS: Our findings suggest that regular and subregular worksite dental check-ups were related to reduction of CDEs. It is important to promote a yearly interval between dental check-ups.

Impact of health literacy on anxiety and depressive symptoms in pregnant women in Japan during the COVID-19 pandemic.

To investigate the relationships between communicative and critical health literacy (CCHL) and anxiety and depressive symptoms (ADs) in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was conducted and 5466 pregnant women responded in Japan in September 2020. A Kessler 6 scale (K6) score ≥ 10, an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13, and four CCHL groups were analyzed using a logistic regression model and trend test. The proportions of pregnant women with a K6 score ≥ 10 and EPDS score ≥ 13 were 13.5 and 15.4%, respectively. In comparisons with the low CCHL group, the adjusted odds ratio (95% CI) for anxiety symptoms was 0.770 (0.604-0.982) in the high CCHL group, while those for depressive symptoms were 0.777 (0.639-0.946), 0.665 (0.537-0.824), and 0.666 (0.529-0.838) in the lower, higher, and high CCHL groups (all p < 0.05), respectively, after adjustments for potential confounding factors, such as age, weeks of gestation, complications, history, number of children, marital status, education, employment, and income. Higher CCHL was associated with significantly lower adjusted odds ratios for anxiety (p for trend = 0.019) and depressive symptoms (p for trend < 0.001). These results suggest a relationship between CCHL and ADs in pregnant women during the COVID-19 pandemic.

Effect of Novel Stratified Lipid Risk by "LDL-Window" and Flow-Mediated Dilation on the Prognosis of Coronary Artery Disease Using the FMD-J Study A Data.

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

Occupational disparities in tumor grade and cytosolic HMGB1 expression in renal cell cancer.

OBJECTIVES: We sought to examine occupational disparities in tumor grade and cytosolic expression of high-mobility group box-1 (HMGB1) among renal cell cancer (RCC) patients. METHODS: This retrospective study included 318 RCC patients with complete information on occupation and pathology in Kanagawa Cancer Registry (KCR). Longest-held occupations were grouped into manual workers (e.g., manufacturing, construction) versus "others." Odds ratios (OR) and 95% confidence intervals (CI) for high-grade histology were estimated by logistic regression, adjusted for age and sex. We also examined a sub-sample of 74 low-grade RCC inpatients to estimate the OR for positive cytosolic HMGB1 expression in manual workers, adjusting for age, sex, and other available covariates. RESULTS: High-grade tumors were more prevalent in manual workers compared to other occupations: 23.0% (14/61) versus 10.9% (28/257, p = .01) with an adjusted OR of 2.28 (95% CI, 1.11-4.69). In the sub-sample of low-grade RCCs, positive cytosolic HMGB1 expression was more prevalent in manual workers compared to other occupations: 71.4% (10/14) versus 38.3% (23/60, p = .03) with a sex- and age-adjusted OR of 3.76 (95% CI, 1.03-13.7). CONCLUSIONS: Manual workers are associated with increased risks of high-grade renal cell tumors and cytosolic HMGB1 expression.

The vaccination status and adverse effects of COVID-19 vaccine among pregnant women in Japan in 2021.

To investigate the vaccination status and adverse reactions to the COVID-19 vaccine among pregnant women in Japan, we conducted an online questionnaire survey from October 5 to November 22, 2021. The number of participants in the online survey was 6576. Of the participants, 4840 (73.6%) were vaccinated twice, and 557 (8.5%) were vaccinated once. A total of 1179 (17.9%) responders had never been vaccinated against COVID-19. The most frequent adverse reaction was local pain at the injection site. The incidence of local adverse reactions was almost identical after the first and the second vaccinations, while systemic reactions, such as fever and fatigue/malaise, and adverse reactions outside the vaccination site such as headache and arthralgia, were more frequent after the second vaccination than after the first vaccination. Regarding the obstetrical complications, uterine tension and/or contraction was observed in 1.65% of the pregnant women after the first vaccination and in 2.98% after the second vaccination, and uterine pain appeared in 1.06% of the pregnant women after the second vaccination. However, serious symptoms, such as hemorrhage, decreased fetal movement, edema, increased blood pressure, and amniorrhexis, were seen in less than 1% of vaccinated women after both the first and second vaccinations. This study clarified the characteristics of vaccination, adverse reactions, and obstetrical symptoms in pregnant women in Japan who had the COVID-19 vaccine up to the second dose. As a booster vaccination is currently underway, further study is needed to improve the management of pregnant women during the current pandemic.

Exploring the contributing factors to multiple chemical sensitivity in patients with migraine.

OBJECTIVE: Multiple chemical sensitivity (MCS) is a form of chemical intolerance in which various systemic symptoms are triggered by exposure to a variety of chemical substances. Although migraine has been associated with central sensitivity syndrome, the relationship between MCS and migraine has not been studied. We assessed the frequency of MCS and its related factors in patients with migraine. METHODS: We performed a cross-sectional study that included 95 patients (14 M/81 F; age, 45.4 ± 12.4 years) out of 100 consecutive patients with migraine from our outpatient headache clinic. MCS was defined as having a combination of Q1 ≥ 30, Q3 ≥ 13, and Q5 ≥ 17 on the quick environment exposure sensitivity inventory (QEESI; Japanese version). Central sensitization inventory-A scores >40 were considered an indication of central sensitization. Headache-related disability and psychological distress were evaluated with the Migraine Disability Assessment score (MIDAS) and Kessler Psychological Distress Scale (K6), respectively. RESULTS: MCS was identified in 20% of patients with migraine; however, none had previously been diagnosed with MCS. The MCS-positive group had higher rates of photophobia, osmophobia, visual aura, sensory aura, and central sensitization and higher MIDAS and K6 scores than the MCS-negative group. A logistic regression analysis showed that osmophobia, sensory aura, and central sensitization were significant contributors to MCS. CONCLUSION: We showed that MCS was observed in 20% of patients with migraine, and our study results may indicate a possible association of MCS with central sensitization and hypersensitivity-related symptoms in patients with migraine.

Characteristics of patients who received helicopter emergency medical services in Japan from 2012 to 2019: a retrospective analysis of data from Tochigi Prefecture.

BACKGROUND: Helicopter Emergency Medical Services (HEMS) has been in operation in Japan since 2001, allowing patients almost anywhere in the nation to receive on-scene emergency treatment from physicians. However, there is insufficient literature on the characteristics of the patients who use Japanese HEMS. Thus, this study aimed to investigate the overall characteristics of patients receiving HEMS care within a single prefecture in Japan. METHODS: We retrospectively analyzed the data of 5163 patients-in Tochigi Prefecture-who received HEMS care from 2012 to 2019. Descriptive statistics were used to analyze the following aspects of care: diagnosis, severity, background characteristics, geographical and environmental variables, immediate pre-hospital intervention, transportation type, and short-term clinical outcomes. RESULTS: Among 7370 HEMS requests received during the study period, treatment was provided to 5163 patients (1.8 cases per day; 3489 men [67.6%]). Nearly 55% (n = 2856) of patients were aged above 60 years. Age peaks were observed at 0-9 years and 60-69 years. The median distance from the base hospital to the site was 26.7 km. The age-standardized rate of HEMS treatment was 30.3 patients per 100,000 people. Cases of trauma and cardiovascular diseases were the most common (65.3%). Most individuals aged 0-9 years and 60-69 years had neurological disease (seizures accounted for 80.5% of this group) and cardiovascular disease, respectively. The number of patients was similar across all four seasons. After immediate pre-hospital intervention, 81.6% of patients receiving HEMS care were transferred by the helicopter ambulance (53.4% and 28.2% to the base hospital and to other hospitals, respectively). Overall, 56.6% of patients receiving HEMS care were transferred to the base hospital, and the short-term recovery rate was above 75%. Intravenous drip and oxygen administration were the most common pre-hospital interventions (93.1% and 72.7%, respectively). CONCLUSIONS: This study is the first to describe the overall characteristics of HEMS patients using comprehensive data of all HEMS patients in one prefecture in Japan. Further research using both local- and national-level data is needed to accelerate the understanding of the benefits of HEMS.

Occupational disparities in survival from common cancers in Japan: Analysis of Kanagawa cancer registry.

BACKGROUND: Little is known about occupational disparities in survival for common cancer sites in Japan. METHODS: Using data from a population-based cancer registry, we identified 32,870 cancer patients diagnosed during 1992-2011. We followed the patients for 5 years (median follow-up time 5.0 years). For each individual, we classified their longest-held occupation into 5 classes (upper non-manual, lower non-manual, manual, farmer, and others) following the Erikson-Goldthorpe-Portocarero scheme. Poisson regression models were used to estimate overall and site-specific mortality rate ratios (MRRs) and 95% confidence intervals (CI) for each occupational class, adjusted for sex, age, and diagnosis year. Upper non-manual workers served as the reference group. Additionally, using a binary categorization of occupations (manual workers versus non-manual workers), a causal mediation analysis with 4-way decomposition was performed to investigate the potential mediation of the association between occupation and overall mortality by cancer stage. RESULTS: Overall prognosis was good in this population (5-year overall survival was 81.7%). Compared with upper non-manual workers, both overall and cancer-specific mortality was higher in lower non-manual workers (MRR=1.14, 95% CI 1.05-1.24) and manual workers (MRR=1.40, 95% CI 1.29-1.53). After adjusting for the mediating influence of prognostic factors (stage and treatment), the observed occupational differences were attenuated but remained significant in manual workers: MRR = 1.23 (95% CI 1.08-1.39). Observed occupational disparities tended to be attributable to common cancers, i.e., stomach and lung among men and female breast cancer. Additionally, manual workers had 1.25 times higher odds for advanced stage. In the mediation analysis, the overall proportion explained by mediating effect of cancer stage was 29% (4% due to mediated interaction and 25% due to pure indirect effect). CONCLUSION: We documented occupational disparities in survival from commonly-occurring cancers in Japan. Occupational differences in cancer stage may explain one-third of the survival disparities.

Adiposity rebound in very-low-birth-weight infants.

OBJECTIVES: Adiposity rebound (AR) refers to an increase in body mass index (BMI) after a nadir. Early AR, in which AR occurs earlier than five years old, is a risk factor for future obesity and metabolic syndrome, but has not been widely studied in very-low-birth-weight infants (VLBWIs). METHODS: The subjects were VLBWIs born in Dokkyo Medical University NICU from January 2008 to December 2010. Height and weight measured at birth and at intervals until seven years old were obtained from medical records. The lowest BMI after one year of age was used for the age of AR. The subjects were divided into those with early and normal AR (<5 and ≥5 years old). BMI percentile at age seven years was compared using the interquartile range (IQR). Changes in BMI were evaluated by repeated measures analysis of variance (ANOVA). RESULTS: There were 38 early AR cases and 62 normal AR cases, giving a prevalence of early AR similar to that in infants with normal birth weight. BMI percentile at age seven years was significantly higher in early AR cases than in normal AR cases (44.6 [IQR: 21.0-79.2] vs. 14.4 [IQR: 3.8-40.8] kg/m2). Changes in BMI were also significantly higher in early AR cases (p=0.024 by ANOVA). CONCLUSIONS: Early AR in VLBWIs is a predictor of future obesity.

Relationship Between Risk of Hyper-Low-density Lipoprotein Cholesterolemia and Evacuation After the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia. METHODS: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013-2015. RESULTS: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise. CONCLUSION: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.