Parenting attitude towards children with autism spectrum disorders: the Japan environment and children's study.

OBJECTIVE: The primary objective of this study was to investigate the parenting attitudes towards children with autism spectrum disorders in early childhood in Japan. DESIGN: This study was a cohort study. The participants were enrolled from January 2011 to March 2014. We obtained the prevalence of autism spectrum disorders at 3 years of age, parenting attitudes and other factors from questionnaires. We divided the participants into two groups, an autism spectrum disorders group and a non-autism spectrum disorders group, and compared the parenting attitudes. SETTING: This study used data from a Japanese birth cohort study: the Japan Environment and Children's Study, conducted across 15 regional centres in Japan. PARTICIPANTS: The full dataset of the Japan Environment and Children's Study comprised 104 059 records. We excluded 17 889 records because the answer for the autism spectrum disorders in the questionnaire was blank. As a result, we analysed the remaining 82 411 mother-child pairs. MAIN OUTCOME MEASURES: The primary outcome variable was parenting attitudes at 3.5 years of age, which was assessed using a questionnaire. We asked respondents 16 questions related to parenting attitudes, and they answered based on their behaviours. The independent variable was the prevalence of autism spectrum disorders at 3 years of age. RESULTS: Of the 82 411 participants, the children with autism spectrum disorders at 3 years of age were 372 (0.45%). In most questions about parenting attitudes, the autism spectrum disorders group had unfavourable responses. The difference was particularly noticeable when the parents taught their children social discipline. Unfavourable parenting attitudes were 16.6% in the autism spectrum disorders group and 0.8% in the non-autism spectrum disorders group in the question item with the largest difference between the two groups, a significant difference. CONCLUSIONS: Parents of children with autism spectrum disorders tended to have unfavourable attitudes, suggesting the importance of parental training.

A Reduction in the Number of Hospitalized Cases of Acute Meningitis during the COVID-19 Pandemic in Japan.

Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the prevalence of acute meningitis before and during the COVID-19 pandemic in Japan. Methods We retrospectively reviewed the Japanese nationwide administrative medical payment system database, Diagnosis Procedure Combination (DPC), from 2016 to 2022. A total of 547 hospitals consistently and seamlessly offered DPC data during this period. The study period was divided into the following three periods: April 2016 to March 2018 (fiscal years 2016-2017), April 2018-March 2020 (2018-2019), and April 2020-March 2022 (2020-2021). Results Among the 28,161,806 patients hospitalized during the study period, 28,399 were hospitalized for acute meningitis: 16,678 for viral/aseptic type, 6,189 for bacterial type, 655 for fungal type, 429 for tuberculous, 2,310 for carcinomatous type, and 2,138 for other or unknown types of meningitis. A significant decrease during the pandemic was confirmed in viral (n=7,032, n=5,775, and n=3,871 in each period; p<0.0001) and bacterial meningitis (n=2,291, n=2,239, and n=1,659; p<0.0001) cases. Meanwhile, no decrease was observed in fungal meningitis (n=212, n=246, and n=197; p=0.056) or carcinomatous meningitis (n=781, n=795, and n=734; p=0.27). The decrease in the number of tuberculous meningitis cases was equivocal (n=166, n=146, and n=117; p=0.014). The decrease during the pandemic was more remarkable in younger populations aged <50 years than in older populations, both for viral and bacterial meningitis. Conclusion The number of hospitalized cases of acute meningitis clearly decreased during the COVID-19 pandemic, especially for viral and bacterial meningitis in younger populations aged <50 years.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075-1.792]), angioma (1.491 [1.079-2.059]), and inguinal hernia (1.746, [1.189-2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261-3.819]) and arrhythmia (1.775, [1.157-2.725]) compared with those with an MBW of 3000-3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052-2.064]), congenital heart disease (1.615, [1.119-2.332]), genital organs (1.648, [1.130-2.405]), hypospadias (1.804, [1.130-2.881]), and inguinal hernia (1.484, [1.189-1.851]) in male infants and CAKUT (1.619, [1.154-2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058-2.877]) and CAKUT (2.470, [1.350-4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

AIMS: This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). METHODS: A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category. RESULTS: Lower maternal birth weight was associated with higher odds of developing early and late gestational diabetes mellitus (P < 0.0001 and P < 0.0001, respectively). The adjusted odds ratios (aORs) for early gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were 1.345 (95% confidence interval [CI]: 0.912-1.984) and 1.338 (95% CI: 1.098-1.629), respectively. The aORs for late gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were, 1.657 (95% CI: 1.298-2.115) and 1.218 (95% CI: 1.058-1.402), respectively. CONCLUSIONS: Regardless of the gestational age when gestational diabetes mellitus was diagnosed, a lower maternal birth weight was associated with an increased risk of gestational diabetes mellitus. Furthermore, the association of a MBW <2500 g with late gestational diabetes mellitus tended to be stronger than that with early gestational diabetes mellitus.

[Academia-Industry Alliance: Recent Trend].

Industry-academia Collaboration is an academic activity within academia(educational institutions such as universities, research institutes, etc.)formed to research and develop new technologies, create new businesses and knowledge, and recruit outsourcing human resources. There is a collaboration between an industry(a private company, a group that engages in broad commercial activities and links research and development directly to economic activity)and academia. Amidst the dramatic changes in the environment surrounding the goals of research and development of new technologies and the creation of new businesses, there are changes in what academia can do complementarily. We will outline the changes and current situation, including the efforts of the Tohoku University Hospital.

Environments affect blood pressure in toddlers: The Japan Environment and Children's Study.

BACKGROUND: The primary objective of this study was to examine risk factors for toddler's hypertension. METHODS: Subjects of this study were children and parents participating in a national birth cohort study in Japan, the Japan Environment and Children's Study. We measured the children's blood pressure (BP) at 2 and 4 years old. We obtained children's and parents' backgrounds from the questionnaire. We investigated the factors that affect BP elevation. RESULTS: Within 4988 participants, the mean systolic BP at 2 years old was 91.2 mmHg for boys and 90.0 mmHg for girls. The mean systolic BP at 4 years old was 93.8 mmHg for boys and 93.1 mmHg for girls. Parental smoking was associated with elevated values of BP at 2 and 4 years old. Obesity, gestational hypertension, and parental lower education were associated with elevated values of BP at 4 years old. Hypertensive group had a significantly higher obesity rate. The mother's lower education and parental smoking were involved in hypertensive groups. CONCLUSION: Parental smoking had a significant effect on BP even in early toddlers. We emphasize the importance of avoiding second-hand smoking from early infancy to prevent future lifestyle-related illnesses including hypertension. IMPACT: The mean systolic BP at 2 years old was 91.2 mmHg for boys and 90.0 mmHg for girls. The mean systolic BP at 4 years old was 93.8 mmHg for boys and 93.1 mmHg for girls. Obesity, parental smoking, and lower education were associated with hypertension at 4 years old. Parental smoking was associated with hypertension at 2 and 4 years old. We emphasize the importance of avoiding second-hand smoking from early infancy.

Timing of Primary Tooth Eruption in Infants Observed by Their Parents.

BACKGROUND: The timing of primary teeth eruption is a visible indicator of infant physical growth other than body weight or height. It also reflects neurological integrity and development as well as nutrition, socioeconomic state, or underlying diseases. Therefore, the timing of primary teeth eruption is one of the major concerns for parents in health checkups for infants and children. However, the detailed developmental timing of teeth eruption differs depending on the survey methodology, country, or generation. We hypothesized that the timing of primary teeth eruption differs between the medical checkup by dentists and the daily records by parents. METHODS: We conducted a questionnaire survey on the date of eruption of primary teeth as an adjunct study among Miyagi Regional Center participants in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. A total of 1695 responses (3793 participants) were analyzed. RESULTS: The median ages of eruption were 7.1 months (male) and 7.6 months (female) for mandibular primary central incisors, 8.7 months (male) and 9.2 months (female) for maxillary primary central incisors, 10.0 months (male) and 10.3 months (female) for maxillary primary lateral incisors, and 10.4 months (male) and 10.8 months (female) for mandibular primary lateral incisors, which were earlier than the reported timings based on dental check-ups. Comparing the eruption time of preterm and term infants, the eruption time was earlier in preterm infants in the corrected ages. CONCLUSIONS: The eruption timing observed and described by the parents is earlier than that examined by dentists at regular check-ups. In addition to examining the primary teeth eruption of full-term birth children, we also examined that of preterm birth children because of the increasing number of premature births. To the best of our knowledge, this is the first report from a large cohort study to clarify the eruption time of primary teeth monitored by parents.

Exploring the efficacy of an educational approach of case-writing for remote learners: insights from a novice writer.

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Factors associated with postpartum smoking relapse at early postpartum period of Japanese women in the Japan Environmental and Children's Study.

BACKGROUND: Postpartum smoking relapse is a serious public health concern. Previous studies have identified several risk factors for postpartum smoking relapse; however, very little is known about the predictors of early postpartum smoking relapse. This study aimed to determine postpartum smoking relapse status and its associated risk factors at 1 month postpartum among Japanese women. METHODS: Data were obtained from 93,851 mothers with live births in an ongoing birth cohort study, the Japan Environment and Children's Study. Data on smoking status and confounding variables were collected using self-administered questionnaires and medical record transcripts. Self-administered questionnaires were administered during the first trimester, second/third trimester, and 1 month after delivery. A multiple logistic regression analysis was performed. RESULTS: Among the 14,326 mothers who smoked during pregnancy, 10,917 (76.2%) quit smoking during pregnancy. Subsequently, 617 (5.7%) of the mothers who had quit relapsed smoking at 1 month postpartum. Maternal age (≤24, ≥35), maternal education (≤12 years), parity (≥Second), feeding method (Formula milk), partner smoking status during pregnancy (Smoker), number of cigarettes per day before the cessation of smoking (≥11), maternal alcohol consumption at 1-month postpartum (Drinker), postpartum depression (EPDS score ≥9), and spending time at the parents' home after delivery (≥14 days) were associated with smoking relapse. CONCLUSIONS: A certain number of mothers relapsed even 1 month postpartum. Besides mother's alcohol and smoking habit before pregnancy, breastfeeding and partner smoking are important factors in early postpartum smoking relapse in Japan.

Incidental Hyperferritinemia in Very Young Infants with Mild Symptoms of COVID-19 Disease.

BACKGROUND: The number of children infected with novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has increased during the outbreak of the Omicron strain. Hyperferritinemia has been reported in severe cases of COVID-19, and in children or neonates with multisystem inflammatory syndrome (MIS). Hyperferritinemia is considered to be one of the signs of MIS, but thus far, there have been few summarized reports on it. We retrospectively analyzed four infants less than 3 months of age with SARS-CoV-2 infections treated in our institution during the outbreak of the Omicron strain. RESULTS: most patients were in good condition, but hyperferritinemia was observed in all of four cases. CONCLUSIONS: Hyperferritinemia can be observed in infantile COVID-19 patients even with mild symptoms. It is necessary to carefully monitor their clinical course and monitor the patients.

Timing of Maternal Smoking Cessation and Newborn Weight, Height, and Head Circumference.

OBJECTIVE: To examine the relationship between timing of smoking cessation during pregnancy and anthropometric indices of newborns. METHODS: Mothers and neonates enrolled in the JECS (Japan Environment and Children's Study), a nationwide birth cohort study, were examined. Patients with full-term neonates were included in the analysis, and 73,025 mother-neonate pairs with complete data were identified. The mothers were classified into six groups according to smoking status during pregnancy (nonsmokers [Q1, n=44,198]; ex-smokers who quit before pregnancy [Q2, n=16,461]; ex-smokers who quit in the first trimester [Q3, n=8,948]; ex-smokers who quit in the second trimester [Q4, n=498]; ex-smokers who quit in the third trimester [Q5, n=651]; and smokers who smoked throughout pregnancy [Q6, n=2,269)]). Data on smoking were based on questionnaires administered in the first, second, or third trimester and 1 month after delivery. The primary outcomes were birth weight, height, and head circumference. RESULTS: Compared with nonsmokers (Q1), no adverse outcomes were observed for ex-smokers who quit before pregnancy (Q2). The mean adjusted weights of male and female neonates were 135 g and 125 g lower, respectively, in Q6 participants than in Q1 participants. Comparing Q1 and Q6 participants, height was 0.6 cm and 0.7 cm smaller for male and female neonates, respectively. Head circumference in neonates of Q6 participants was 0.3 cm and 0.3 cm smaller for male and female neonates, respectively, than that in Q1 participants. Across all three measures, smoking cessation in the first and second trimester reduced the differential in outcomes between nonsmokers and individuals who smoked throughout pregnancy. CONCLUSION: Smoking during pregnancy is associated with reduced newborn birth weight, height, and head circumference. Earlier smoking cessation during pregnancy reduces the adverse effects of smoking on fetal growth.

Male infant with Noonan syndrome with RAF-1 gene mutation who survived hypertrophic cardiomyopathy-induced fatal heart failure and uncontrollable arrhythmias.

Noonan syndrome (NS) is a congenital disease with characteristic facial features as well as heart disease, short stature and thoracic abnormalities. More than eighty per cent of patients with NS show several cardiac disorders including pulmonary valvular stenosis, hypertrophic cardiomyopathy (HCM) and/or atrial septal defects. HCM is a serious cardiac comorbidity in patients with NS, especially in those who are diagnosed within 6 months of age with congestive heart failure. Arrhythmia with or without HCM in NS is a rare comorbidity with a complicated clinical course and poor prognosis.In this manuscript, we present the case of a male infant with NS with RAF1 gene mutation, who showed various types of arrhythmias. He developed life-threatening heart failure and uncontrollable arrhythmias. We attempted several antiarrhythmic agents and finally controlled the arrhythmias to establish a normal sinus rhythm with a combination of amiodarone and flecainide.

Two Distinct Cases of Adult-onset Kawasaki Disease.

Kawasaki disease (KD) is a systemic vasculitis syndrome that mostly affects children under 4 years old. Among the reported KD cases, only 1% were over 10 years old. We herein report 2 cases of adult-onset KD (AKD) in 19- and 17-year-old boys diagnosed with a persistent fever and cervical lymphadenitis. Both patients showed cardiac complications, such as coronary artery dilation and myocarditis. Repeated intravenous immunoglobulin therapy was effective in the 19-year-old, while plasma exchange therapy was needed for the 17-year-old, with no sequelae noted at discharge. KD should be considered as a differential diagnosis for persistent fever in adults.

Bilateral lung transplantation in a 9-year-old girl with bronchopulmonary dysplasia with pulmonary hypertension.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9-year-old girl who developed PH associated with severe BPD (BPD-PH) and underwent bilateral lung transplantation (BLTx). Case description A 9-year-old girl was admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 g. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD-PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life-threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground-glass opacities and emphysematous low-density areas in the upper and lower lobes. BLTx from a brain-dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration, and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. CONCLUSION: This is the first case report of BLTx in a pediatric, irreversible BPD-PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD-PH.

Thoracic Empyema Secondary to Congenital Chylothorax in a 14-Month-Old Boy with Noonan Syndrome.

Thoracic empyema usually occurs as a complication of bacterial pneumonia, but in rare cases, it is caused by hematogenous dissemination secondary to nonpulmonary diseases. Congenital chylothorax or chylothorax in children is associated with maldevelopment of the lymphatic system, nonimmune hydrops fetalis, several syndromes including Down syndrome, Noonan syndrome, or Turner syndrome, a complication of thoracic surgery, right heart failure with high central venous pressure, or tumors. There are very few reports of empyema associated with preexisting chylothorax. In the present study, we describe a rare case of thoracic empyema associated with congenital chylothorax and supravalvular pulmonary stenosis associated with clinically diagnosed Noonan syndrome. It is necessary to closely monitor patients with chylothorax because they are at risk of developing severe lung infections, such as pleural empyema or lung abscesses.

Extracellular-Matrix-Reinforced Bioinks for 3D Bioprinting Human Tissue.

Recent advances in 3D bioprinting allow for generating intricate structures with dimensions relevant for human tissue, but suitable bioinks for producing translationally relevant tissue with complex geometries remain unidentified. Here, a tissue-specific hybrid bioink is described, composed of a natural polymer, alginate, reinforced with extracellular matrix derived from decellularized tissue (rECM). rECM has rheological and gelation properties beneficial for 3D bioprinting while retaining biologically inductive properties supporting tissue maturation ex vivo and in vivo. These bioinks are shear thinning, resist cell sedimentation, improve viability of multiple cell types, and enhance mechanical stability in hydrogels derived from them. 3D printed constructs generated from rECM bioinks suppress the foreign body response, are pro-angiogenic and support recipient-derived de novo blood vessel formation across the entire graft thickness in a murine model of transplant immunosuppression. Their proof-of-principle for generating human tissue is demonstrated by 3D bioprinting human airways composed of regionally specified primary human airway epithelial progenitor and smooth muscle cells. Airway lumens remained patent with viable cells for one month in vitro with evidence of differentiation into mature epithelial cell types found in native human airways. rECM bioinks are a promising new approach for generating functional human tissue using 3D bioprinting.

Wnt/ß-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema.

Wnt/ß-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/ß-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/ß-catenin responsive progenitor cells and the potential impact of Wnt/ß-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used TCF/Lef:H2B/GFP reporter mice to investigate the role of Wnt/ß-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/ß-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt/ß-catenin activity was required for the initiation of multiple subtypes of distal lung organoids derived from the Wntlow epithelial progenitors. Further ectopic Wnt/ß-catenin activation specifically led to an increase in alveolar organoid number; however, the subsequent proliferation of alveolar epithelial cells in the organoids did not require constitutive Wnt/ß-catenin signaling. Distal lung epithelial progenitor cells derived from the mouse model of elastase-induced emphysema exhibited reduced organoid forming capacity. This was rescued by Wnt/ß-catenin signal activation, which largely increased the number of alveolar organoids. Together, our study reveals a novel mechanism of lung epithelial progenitor cell activation in homeostasis and emphysema.

Improving the viability of tissue-resident stem cells using an organ-preservation solution.

Human clinical specimens are a valuable source of tissue-resident stem cells, but such cells need to be collected immediately after tissue collection. To extend the timescale for collection from fresh human samples, we developed a new extracellular fluid (ECF)-type preservation solution based on a high-sodium and low-potassium solution containing low-molecular-weight dextran and glucose, which is used for preservation of organs for transplantation. In this study, we compared the preservation of tissue-resident stem cells using our ECF solution with that using three other solutions: PBS, Dulbecco's modified Eagle's medium and Euro-Collins solution. These solutions represent a common buffer, a common culture medium and a benchmark organ-preservation solution, respectively. Lung tissues were removed from mice and preserved for 72 h under low-temperature conditions. Of the solutions tested, only preservation in the ECF-type solution could maintain the proliferation and differentiation capacity of mouse lung tissue-resident stem cells. In addition, the ECF solution could preserve the viability and proliferation of human alveolar epithelial progenitor cells when stored for more than 7 days at 4 °C. The mean viability of human alveolar type II cells at 2, 5, 8 and 14 days of low-temperature preservation was 90.9%, 84.8%, 85.7% and 66.3%, respectively, with no significant differences up to 8 days. Overall, our findings show that use of our ECF-type preservation solution may maintain the viability and function of tissue-resident stem cells. Use of this preservation solution may facilitate the investigation of currently unobtainable human tissue specimens for human stem cell biology.

Preoperative administration of propranolol reduced the surgical risks of PHACES syndrome in a 14-month-old girl.

PHACES syndrome is an uncommon neurocutaneous disorder first identified in 1996. Patients with PHACES syndrome often require surgical treatment for their anomalies, including intracranial vasculopathy, coarctation/interruption of the aorta, intracardiac defects, glaucoma/cataract and sternal defects. Risk factors associated with the symptoms of intraoperative/perioperative management include ischaemic stroke due to the cerebral vasculopathy, airway obstruction due to the subglottic/tracheal haemangiomas and massive bleeding due to the large haemangiomas. Recently, propranolol is considered as first-line therapy for patients with infantile haemangiomas (IHs). However, until now, there have been no reported cases of PHACES syndrome treated by propranolol to reduce the surgical risks associated with IH. In this report, we describe a case of a 14-month-old Japanese girl with PHACES syndrome treated by propranolol for IH before surgical closure of the ventricular septum defect. Oral administration of propranolol was effective in decreasing the size of IH, leading to the uneventful perioperative course.