Impact of Changes in Lifestyle and Psychological Factors on the Incidence of Metabolic Syndrome after the Great East Japan Earthquake: Follow-up of the Fukushima Health Management Survey.

AIM: The Fukushima Daiichi Nuclear Power Plant accident caused lifestyle changes and psychological distress in residents living near the plant. This study clarified the associations between changes in residents' lifestyles and psychological factors with the onset of metabolic syndrome (METs) after the accident. METHODS: This longitudinal study included 10,373 residents who underwent the Comprehensive Health Check and Mental Health and Lifestyle Survey in Fiscal Year (FY) 2013. Follow-up surveys were conducted between FY 2014 and FY 2017. Lifestyle changes and the METs incidence were evaluated using a logistic regression model. RESULTS: METs developed in 14.0% of subjects. In addition to metabolic factors, such as the body mass index, hypertension, dyslipidemia, and diabetes mellitus, there were differences in physical activity, fast walking, eating fast, eating habits before bedtime, skipping breakfast, current smoking, and alcohol intake between subjects with and without new-onset METs. Eating fast, current smoking, and drinking alcohol were positively associated with new-onset METs, whereas starting physical activity and fast walking were inversely associated with new-onset METs. CONCLUSIONS: Disaster-related lifestyle changes, such as eating fast, starting to smoke, and continued alcohol intake, were risk factors for new-onset METs after the Fukushima Daiichi Nuclear Power Plant accident.

Comparison of mutations in human parainfluenza viruses during passage in primary human bronchial/tracheal epithelial air-liquid interface cultures and cell lines.

Human parainfluenza virus (HPIV) causes respiratory infections, which are exacerbated in children and older people. Correct evaluation of viral characteristics is essential for the study of countermeasures. However, adaptation of viruses to cultured cells during isolation or propagation might select laboratory passage-associated mutations that modify the characteristics of the virus. It was previously reported that adaptation of HPIV3, but not other HPIVs, was avoided in human airway epithelia. To examine the influence of laboratory passage on the genomes of HPIV1-HPIV4, we evaluated the occurrence of mutations after passage in primary human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) culture and conventional cultured cells (Vero cells expressing the transmembrane protease, serine 2, and normal Vero cells). The occurrence of mutations was significantly lower in HBTEC-ALI than in conventional culture. In HBTEC-ALI culture, most of the mutations were silent or remained at low variant frequency, resulting in less impact on the viral consensus sequence. In contrast, passage in conventional culture induced or selected genetic mutations at high frequency with passage-associated unique substitutions. High mutagenesis of hemagglutinin-neuraminidase was commonly observed in all four HPIVs, and mutations even occurred in a single passage. In addition, in HPIV1 and HPIV2, mutations in the large protein were more frequent. These results indicate that passage in HBTEC-ALI culture is more suitable than conventional culture for maintaining the original characteristics of clinical isolates in all four HPIVs, which can help with the understanding of viral pathogenesis. IMPORTANCE: Adaptation of viruses to cultured cells can increase the risk of misinterpretation in virological characterization of clinical isolates. In human parainfluenza virus (HPIV) 3, it has been reported that the human airway epithelial and lung organoid models are preferable for the study of viral characteristics of clinical strains without mutations. Therefore, we analyzed clinical isolates of all four HPIVs for the occurrence of mutations after five laboratory passages in human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) or conventional culture. We found a high risk of hemagglutinin-neuraminidase mutagenesis in all four HPIVs in conventional cultured cells. In addition, in HPIV1 and HPIV2, mutations of the large protein were also more frequent in conventional cultured cells than in HBTEC-ALI culture. HBTEC-ALI culture was useful for maintaining the original sequence and characteristics of clinical isolates in all four HPIVs. The present study contributes to the understanding of HPIV pathogenesis and antiviral strategies.

Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.

Recent Status of Phase I Clinical Trials for Brain Tumors: A Regulatory Science Study of Exploratory Efficacy Endpoints.

BACKGROUND: Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs. METHODS: Using Clarivate's Cortellis™, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B). RESULTS: Selected studies included a median of 1.5 PEs (range, 1-6) and 5 SEs (range, 0-19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039). CONCLUSIONS: Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.

Safety of romiplostim administered immediately after cord-blood transplantation: a phase 1 trial.

Graft failure and delayed hematopoietic recovery are the major limitations of cord-blood transplantation (CBT). Romiplostim, a thrombopoietin-receptor agonist, promotes megakaryopoiesis and multilineage hematopoiesis in aplastic anemia. The decreased number of hematopoietic stem cells in the early phase after CBT and aplastic anemia share certain characteristics. Therefore, we hypothesized that romiplostim administration immediately after CBT may promote multilineage hematopoietic recovery. We investigated the safety and preliminary efficacy of administering romiplostim a day after CBT. This phase 1 dose-escalation study included six adults with hematologic malignancies in remission. Romiplostim was administered subcutaneously within 7 days after single-unit CBT, initially at doses of 5 µg/kg or 10 µg/kg in three patients, then once a week for 14 weeks or until platelet recovery. The maximum dose was 20 µg/kg. The median number of romiplostim administrations was 6 (range, 3-15). Romiplostim-related adverse events included bone pain (3/6) and injection site reaction (1/6). Non-hematological grade ≥ 3 toxicities were observed in four patients; febrile neutropenia was the most common (4/6). All patients achieved neutrophil engraftment and the median time was 14 days (range, 12-32). Platelet counts ≥ 50 × 109 /L were recorded in all patients except for one who died on day 48; the median time was 34 days (range, 29-98). No relapse, thrombosis, or bone marrow fibrosis was observed during a median follow-up of 34 months. Romiplostim may be safely administered in the early phase of CBT. Further phase 2 trial is warranted for its efficacy evaluation. Trial registration number: UMIN000033799, August 18, 2018.

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial.

PURPOSE: To evaluate the safety and pathologic complete response (pCR) rate of radiation therapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer. METHODS AND MATERIALS: A multicenter, phase 2 study was conducted with patients with clinically T2-3 or very-high-risk T1 bladder cancer who were poor candidates for or refused radical cystectomy. The interim analysis of pCR is reported as a key secondary endpoint ahead of the progression-free survival rate primary endpoint. Radiation therapy (41.4 Gy to the small pelvic field and 16.2 Gy to the whole bladder) was given in addition to 1200 mg intravenous atezolizumab every 3 weeks. After 24 treatment weeks, response was assessed after transurethral resection, and tumor programmed cell death ligand-1 (PD-L1) expression was assessed using tumor-infiltrating immune cell scores. RESULTS: Forty-five patients enrolled from January 2019 to May 2021 were analyzed. The most common clinical T stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were solitary (77.8%), small (<3 cm) (57.8%), and without concurrent carcinoma in situ (88.9%). Thirty-eight patients (84.4%) achieved pCR. High pCR rates were achieved in older patients (90.9%) and in patients with high PD-L1-expressing tumors (95.8% vs 71.4%). Adverse events (AEs) occurred in 93.3% of patients, with diarrhea being the most common (55.6%), followed by frequent urination (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3%, whereas no grade 4 AEs were observed. CONCLUSIONS: Combination therapy with radiation therapy and atezolizumab provided high pCR rates and acceptable toxicity, indicating it could be a promising option for bladder preservation therapy.

Prevalence and metronidazole resistance of Trichomonas vaginalis among Japanese women in 2021.

Objectives: Trichomonas vaginalis is the most prevalent sexually transmitted parasite worldwide. However, no surveillance system exists to monitor T. vaginalis cases and drug resistance in Japan. Methods: Cervical cytology vaginal swabs were collected from women with and without suspected symptoms of T. vaginalis infection; these swabs were used for the detection of T. vaginalis, human papillomavirus (HPV), and Candida albicans using specific polymerase chain reaction. Clinical isolates of T. vaginalis were subjected to metronidazole susceptibility tests using the previously reported minimal lethal concentration (MLC) and newly established half-maximal inhibitory concentration (IC50) values. Results: The prevalence of T. vaginalis in the study population was 4.2% (5/119; 95% confidence interval [Cl], 1.5-9.7). Additionally, asymptomatic infection constituted 60% (3/5) of all cases of T. vaginalis infection. All T. vaginalis-positive patients were coinfected with HPV but not C. albicans. Five clinical T. vaginalis isolates showed metronidazole susceptibility, which was evaluated using MLC values. The quantitative IC50 values revealed that two of these clinical isolates exhibited a decreased metronidazole susceptibility. Conclusion: This is the first study to demonstrate the prevalence of T. vaginalis in Japanese women. The IC50 values of metronidazole against T. vaginalis enabled the precise and quantitative evaluation of metronidazole-susceptible T. vaginalis.

Congenital Anomalies in Infants in Fukushima from 2011 to 2014: The Japan Environment and Children's Study.

Introduction: This study aimed to assess congenital anomalies among infants from 2011 to 2014 in Fukushima and compare the assessment with that from other geographical regions in Japan. Methods: We used the dataset of the Japan Environment and Children's Study (JECS), which is a nationwide prospective birth cohort study. For the JECS, participants were recruited through 15 regional centers (RC), including Fukushima. Pregnant women were recruited between January 2011 and March 2014. The Fukushima RC recruited all municipalities in the Fukushima Prefecture, from where we compared congenital anomalies in infants from the Fukushima RC to those in the infants from 14 other RCs. Crude and multivariate logistic regression analyses were also performed, with the multivariate logistic regression analysis being adjusted for maternal age, maternal body mass index (kg/m2), infertility treatment, multiple pregnancies, maternal smoking, maternal alcohol consumption, pregnancy complications, maternal infection, and infant sex. Results: In the Fukushima RC, 12,958 infants were analyzed, and 324 infants were diagnosed with major anomalies (2.50%). In the remaining 14 RCs, 88,771 infants were analyzed and 2,671 infants were diagnosed with major anomalies (3.01%). Crude logistic regression analysis demonstrated that the odds ratio for the Fukushima RC was 0.827 (95% confidence interval, 0.736-0.929) using the other 14 RCs as a reference. Multivariate logistic regression analysis also demonstrated that the adjusted odds ratio was 0.852 (95% confidence interval, 0.757-0.958). Conclusions: Fukushima Prefecture was found not to be an area at high risk for the occurrence of congenital anomalies in infants compared nationwide in Japan from 2011 to 2014.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Efficacy Endpoints in Phase II Clinical Trials for Meningioma: An Analysis of Recent Clinical Trials.

BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST)-based response rates are commonly used as efficacy endpoints in phase II clinical trials for solid tumors. However, no consensus has been reached concerning adequate efficacy endpoints for phase II clinical trials targeting meningioma. Irregularity of lesions after resection, and varying degrees of dysplasia and histologic subtypes make establishing an appropriate efficacy evaluation difficult. METHODS: We analyzed primary efficacy endpoints (PEEs) and background factors from 48 trials retrieved from ClinicalTrials.gov ( https://clinicaltrials.gov/ ) using the search criteria "meningioma," "interventional," "phase II," and "study start 4/1/2001 to 3/31/2021." Primary purpose of the study was efficacy endpoint setting in overall population and three subgroups. RESULTS: Among 45 PEEs set in the 39 trials included; 33 trials with single PEE, and six trials with double PEEs, 17/45 (38%) trials adopted progression-free survival (PFS) rate, 15/45 (33%) trials response rate (seven Macdonald criteria or modified, three RECIST, three volumetric estimation, one RANO criteria, one unknown), 10/45 (22%) PFS, 1/45 (2%) OS, and 2/45 (4%) other endpoints. Although 26 PEEs were time-to-event endpoints, 19 of the 26 PEEs were single-arm studies. CONCLUSIONS: Time-to-event efficacy endpoints were often compared to historical data, and two-dimensional evaluation is more suitable than one-dimensional one. Accumulation of prognostic data is essential to standardize time-to-event efficacy endpoints. Considering the difficulty of setting design for phase II clinical studies targeting meningioma, evaluation might be done with multiple efficacy endpoints.

Tobacco Exposure During Pregnancy and Infections in Infants up to 1 Year of Age: The Japan Environment and Children's Study.

BACKGROUND: Tobacco exposure during pregnancy is associated with several adverse outcomes in infants. We investigated the association between tobacco exposure during pregnancy (both active and second-hand) and various infections in infants up to 1 year. METHODS: This prospective cohort study used a fixed dataset (jecs-an-20180131) from the Japan Environment and Children's Study of registered births in Japan during 2011-2014 that included 104,065 fetal records from enrolled pregnant women. Based on the participants' responses to the questionnaire on smoking status, mothers were first divided into "never smoked," "quit smoking," and "current smoker" groups and then into "no second-hand smoking (SHS)" and "SHS" groups. Infectious diseases included central nervous system infection, otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastroenteritis (GI), and urinary tract infection. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis and adjusted for maternal, socioeconomic, and postnatal confounding factors. RESULTS: Among the 73,205 newborns enrolled, multivariable analysis revealed that the aOR of LRTI and GI was 1.20 (95% CI, 1.07-1.33) and 1.18 (95% CI, 1.04-1.35), respectively, for the "current smoker with/without SHS" group compared with the "never smoked without SHS" group. "Quit smoking without SHS" was not associated with the risk of LRTI. SHS was associated with an increased risk of OM, URTI, LRTI, and GI, especially with LRTI and GI. CONCLUSION: Exposure to tobacco smoke during pregnancy was associated with an increased risk of OM, URTI, LRTI, and GI in infants during their first year of life.

Association of Chlamydia trachomatis infection with pregnancy outcomes among Japanese pregnant women: The Japan environment and children's study.

This study aimed to investigate the impact of Chlamydia trachomatis (CT) infection on pregnancy outcome in pregnant Japanese women. We utilized the data from a nationwide birth cohort study, the Japan Environment and Children's Study (JECS), for this study. We enrolled 26,385 individuals who could refer to data on pregnancy outcomes and confounding factors, with data on CT. Binominal logistic regression models were used to determine whether pregnant women with CT positivity were at more risk of experiencing adverse pregnancy outcomes, preterm birth (PTB), preterm prelabor rupture of membrane (pPROM), low birth weight (LBW) infants, small for gestational age (SGA) births, or hypertensive disorders of pregnancy (HDP). After adjusting for maternal age, parity, marital status, smoking status, and education status, there were no significantly increased risks of PTB, pPROM, LBW infants, SGA, and HDP in the odds ratios. No significant increase in the risk of adverse pregnancy outcomes was observed in any of the subgroup analyses, which were limited to the pregnancy women in Fukushima prefecture, where CT screening could be confirmed at 28-30 weeks of gestation. We believe that the results of this study will make a significant contribution to the future of medical care for pregnant women in Japan. Our findings are important for medical practitioners to contribute to the future medical treatment of Japanese pregnant women, and also to contribute to pre-conception care for Japanese society as a whole, including pregnant women.

Maternal Urinary Cotinine Concentrations During Pregnancy Predict Infant BMI Trajectory After Birth: Analysis of 89617 Mother-Infant Pairs in the Japan Environment and Children's Study.

Background: Clinical or epidemiological conclusions remain undecided on the direct effects of active and second-hand smoking during pregnancy on childhood obesity. Urinary cotinine (UC) concentration, an accurate and quantitative marker for smoking, may elucidate the dose-dependent relationship between smoking during pregnancy and childhood obesity. To analyze the relationship between UC concentration and smoking questionnaire (SQ) classes for active and second-hand smoking in pregnant mothers and trajectory of infant Kaup index (body mass index: BMI). Methods: This multicenter prospective cohort study was conducted using a list-wise complete set of 35829 among 89617 mother-infant singleton pairs, recruited between 2011 and 2014, in the Japan Environment and Children's Study (JECS). Pairs were categorized according to UC levels (1 to 4 classes) or SQ (0 to 4 classes). Results: Maternal BMI at delivery was the highest in UC class 4 (highest). Maternal and paternal education of ≥16 years and annual household income were lowest in UC class 4. Infant BMI was lower at birth, but trends in BMI and ΔBMI were higher from six to 36 months step-wise in the UC classes. The above tendency was observed in the list-wise complete dataset but was emphasized after multiple imputations and corrections of cofounders. UC concentration in five SQ classes largely fluctuated, and the relationship between SQ classes and trends in BMI and ΔBMI was not statistically significant. Conclusion: Infants from high UC mothers had a low BMI at birth, increasing from six to 36 months of age. UC concentrations, but not smoking questionnaire classes, predict infant BMI trajectory, suggesting that active and second-hand smoking affect child obesity in a dose-dependent manner.

Changes in virus detection in hospitalized children before and after the severe acute respiratory syndrome coronavirus 2 pandemic.

The impact of strengthening preventive measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the prevalence of respiratory viruses in children was examined. After the SARS-CoV-2 pandemic, the rate of multiple virus detection among hospitalized children decreased. Immediately after the SARS-CoV-2 pandemic, respiratory syncytial and parainfluenza viruses were rarely detected and subsequently reemerged. Human metapneumovirus and influenza virus were not consistently detected. Non-enveloped viruses (bocavirus, rhinovirus, and adenovirus) were detected to some extent even after the pandemic. Epidemic-suppressed infectious diseases may reemerge as susceptibility accumulates in the population and should continue to be monitored.

Association of preconception dysmenorrhea with obstetric complications: the Japan Environment and Children's Study.

BACKGROUND: The association of maternal preconception dysmenorrhea, especially primary dysmenorrhea, with obstetric complications has not been clearly described. Therefore, we evaluated the association of preconception dysmenorrhea with obstetric complications while accounting for the presence of pelvic pathologies. METHODS: We analyzed the data of women with singleton live births at and after 22 weeks of gestation enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study, between 2011 and 2014. Participants with psychological disorders were excluded. Preconception dysmenorrhea, identified in the medical record transcripts, was categorized into mild dysmenorrhea (MD) and severe dysmenorrhea (SD). Furthermore, excluding those who had pelvic pathologies via self-reported questionnaires (endometriosis, adenomyosis, and uterine myomas) with MD and SD, preconception dysmenorrhea was categorized into mild primary dysmenorrhea (MPD) and severe primary dysmenorrhea (SPD), respectively. Using multiple logistic regression, adjusted odds ratios (aORs) for obstetric complications, including preterm birth (PTB) before 37 weeks and 34 weeks, small-for-gestational-age infants, preterm premature rupture of membrane, and hypertensive disorders of pregnancy, were calculated (considering confounders) in women with (1) MD or SD and (2) MPD or SPD. Women without preconception dysmenorrhea were used as a reference. RESULTS: A total of 80,242 participants were analyzed. In women with SD, the aOR for PTB before 37 weeks was 1.38 (95% confidence interval [CI] 1.10, 1.72). In women with SPD, the aOR for PTB before 37 weeks was 1.32 (95% CI 1.02, 1.71). There was no association between women with MD or MPD and obstetric complications. CONCLUSIONS: SD and SPD are significantly associated with an increased incidence of PTB before 37 weeks. Care providers should provide proper counseling regarding the association between preconception dysmenorrhea and obstetric complications. Optimal management of pregnant women with preconception dysmenorrhea to reduce the incidence of PTB should be elucidated in further studies, with detailed clinical data of pelvic pathologies.

Can serum periostin predict bronchopulmonary dysplasia in premature infants?

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD. METHODS: A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006). CONCLUSIONS: Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants. IMPACT: This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.

Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7 ±â€…4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

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.

Influence of Maternal Active and Secondhand Smoking during Pregnancy on Childhood Obesity at 3 Years of Age: A Nested Case-Control Study from the Japan Environment and Children's Study (JECS).

Maternal smoking during pregnancy is a risk factor for childhood obesity; however, the combined effect of secondhand smoking during pregnancy on children in the early years is unclear. We examined the effects of maternal active and secondhand smoking during pregnancy on childhood obesity in a large population-based cohort. A nested case-control study originating from the Japan Environment and Children's Study was performed. The maternal smoking status was collected via self-administered questionnaires during mid/late pregnancy. Obesity in children was determined based on BMI measured at 3 years of age. In total, 4875 cases and 19,491 controls were included in the analyses. Conditional logistic regression models with a significance level of 5% (two-tailed test) were used to test the association. The proportion of mothers who continued smoking and who were exposed to secondhand smoking daily during pregnancy were 3.9% and 13.0% in cases and 2.9% and 10.8% in controls, respectively. Continuous maternal smoking was associated with increased odds of obesity compared to those who never smoked or quit smoking before the pregnancy (adjusted odds ratio, 1.39; 95% confidence interval, 1.01-1.92). The odds increased further when combined with secondhand smoking. The promotion of non-smoking among family members, in public and workplace could benefit pregnant women and offspring.