Automated escape system: identifying prey's kinematic and behavioral features critical for predator evasion.

Identifying the kinematic and behavioral variables of prey that influence evasion from predator attacks remains challenging. To address this challenge, we have developed an automated escape system that responds quickly to an approaching predator and pulls the prey away from the predator rapidly, similar to real prey. Reaction distance, response latency, escape speed and other variables can be adjusted in the system. By repeatedly measuring the response latency and escape speed of the system, we demonstrated the system's ability to exhibit fast and rapid responses while maintaining consistency across successive trials. Using the live predatory fish species Coreoperca kawamebari, we show that escape speed and reaction distance significantly affect the outcome of predator-prey interactions. These findings indicate that the developed escape system is useful for identifying kinematic and behavioral features of prey that are critical for predator evasion, as well as for measuring the performance of predators.

Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Teenage and young adult pregnancy and depression: findings from the Japan environment and children's study.

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression.

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.

Association of soap use when bathing 18-month-old infants with the prevalence of allergic diseases at age 3 years: The Japan Environment and Children's Study.

BACKGROUND: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. METHODS: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18-month-old infants and the prevalence of allergic diseases when they were aged 3 years. RESULTS: Data for 74,349 children were analyzed. Most 18-month-old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05-1.34; sometimes: aOR 1.72, 95% CI 1.46-2.03; seldom: aOR 1.99, 95% CI 1.58-2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. CONCLUSIONS: Frequent soap use when bathing 18-month-old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well-designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases.

Maternal magnesium intake and childhood wheezing in offspring at 3 years of age: the Japan Environment and Children's Study.

This study evaluated the association between maternal magnesium intake (MMI) and childhood wheezing incidence in 3-year-old offspring. We hypothesised that higher MMI imparts anti-inflammatory and antioxidant effects that decrease childhood wheezing incidence in offspring. Data of 79 907 women (singleton pregnancy, ≥ 22 weeks) from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were categorised into quintiles of MMI (< 148·00, 148·00-187·99, 188·00-228·99, 229·00-289·99 and ≥ 290·00 mg/d), quintiles of adjusted MMI for daily energy intake (aMMI) (< 0·107, 0·107-0·119, 0·120-0·132, 0·133-0·149 and ≥ 0·150 mg/kcal) and MMI levels either below or above the ideal value (< 310·00 or ≥ 310·00 mg/d). Multivariable logistic regression analysis was performed to calculate OR for the incidence of childhood wheezing in offspring among participants in each MMI category, with the lowest MMI group considered the reference group. Maternal demographic, socio-economic, medical and other nutrient intake backgrounds were considered potential confounding factors. The adjusted OR (aOR) for childhood wheezing in the offspring of women with the highest MMI was 1·09 (95 % CI, 1·00, 1·20), whereas that calculated based on aMMI categories and offspring of women with above-ideal MMI levels remained unchanged. The highest MMI was associated with slightly increased childhood wheezing incidence in the offspring. MMI during pregnancy had an insignificant clinical impact on this incidence; moreover, modifying MMI would not significantly improve childhood wheezing incidence in offspring. Therefore, further studies should clarify the association between other prenatal factors and childhood wheezing incidence in offspring.

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.

Cord blood triglyceride and total cholesterol in preterm and term neonates: reference values and associated factors from the Japan Environment and Children's Study.

This study aimed to investigate the associations between cord serum total cholesterol (TC) and triglyceride (TG)levels and perinatal factors and determine the reference levels of cord blood TC and TG in Japanese neonates. This was a prospective birth cohort study using data from the Japan Environment and Children's Study, which included data on births from 2011 to 2014 in Japan. TC and TG levels were determined in cord blood samples. A total of 70,535 pairs of neonates (male: 36,001, female: 34,524) and mothers were included. The mean cord blood TC and TG levels were 72.2 mg/dL and 24.4 mg/dL, respectively. Multiple regression analyses revealed that gestational age and birth weight were significantly associated with cord blood TC (coefficient -2.35, 95% confidence interval [CI] -2.40 - -2.22 and coefficient 0.002, 95% CI 0.002-0.003, respectively) and TG (coefficient 3.09, 95% CI 3.01-3.17 and coefficient - 0.009, 95% CI - 0.009-0.008, respectively) levels. Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories.    Conclusion: Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories in Japanese newborns. Maternal complications such as maternal parity, HDP, PROM, maternal obesity and income level were associated with cord TC and TG levels. What is Known: • No studies have ascertained the reference levels of cord blood lipid levels in Japan. What is New: • Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term.

Association of Maternal Asthma and Total Serum Immunoglobulin E levels with Obstetric Complications: The Japan Environment and Children's Study.

OBJECTIVE: To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. METHODS: Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22 weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40 IU/mL), moderate IgE levels (52.40-331.00 IU/mL), and high IgE levels (> 331.00 IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. RESULTS: The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05-1.50) and 1.33 (95% CI, 1.06-1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73-0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04-1.52). CONCLUSIONS FOR PRACTICE: MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA.

What is Already Known on this Subject? Maternal asthma (MA) is associated with several obstetric complications, including preterm births (PTB), small for gestational age (SGA) infants, and hypertensive disorders of pregnancy (HDP). Few studies with data from nationwide cohorts have elucidated the association between MA and obstetric complications comprehensively while accounting for the subdivided objective biomarkers of MA.What this Study Adds? MA with subdivided total serum IgE levels was associated with various obstetric complications. Total serum IgE level may be a potential prognostic marker for pregnant women with MA to predict the potential risk of PTB, SGA infants, and HDP.

Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in Caenorhabditis elegans.

Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the Caenorhabditis elegans homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings suggest that valence-encoding interneuronal activity is determined by a presynaptic mechanism whereby MAST kinase, Stomatin, and Diacylglycerol kinase influence presynaptic outputs.

Influence of post-disaster evacuation on childhood obesity and liver dysfunction: The Fukushima Health Management Survey.

BACKGROUND: After the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident in 2011, the Fukushima Prefectural Government launched a long-term health management survey for the population of Fukushima. Results of the Comprehensive Health Check (CHC) showed that some children aged 6-15 years, who resided in the evacuation area at the time of the disaster, had obesity, hyperlipidemia, liver dysfunction, and/or renal dysfunction from as early as 2011. The aim of the present study was to determine the long-term trend of obesity and hepatic enzyme abnormalities in Fukushima children. METHODS: We evaluated the changes in body mass index standard deviation score (BMI-SDS), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase from 2011 to 2018. RESULTS: Obesity (BMI-SDS ≥ 2) was significantly associated with hepatobiliary enzyme abnormalities. The mean BMI-SDS was significantly higher in 2011 after the disaster, but then soon showed a gradual decrease. The frequency of obesity did not increase significantly after the disaster. There were no significant differences in the prevalence of hepatobiliary enzyme abnormalities in the children aged 6-15 years of either sex from 2011 to 2018. CONCLUSIONS: In the present study, we found that the increase in the mean BMI-SDS after the disaster was temporary, suggesting that the frequency of obesity and liver dysfunction might not have been significantly influenced by the disaster.

Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.

BACKGROUND: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. METHODS: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. RESULTS: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. CONCLUSION: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.

Influence of preconception carbohydrate intake on hypertensive disorders of pregnancy: The Japan Environment and Children's Study.

AIM: Hypertensive disorders of pregnancy (HDP) are a crucial cause of morbidity and mortality. We aimed to examine whether preconception carbohydrate intake is associated with new-onset HDP and small for gestational age (SGA) births. METHODS: We identified 93 265 normotensive (primiparous, 37 387; multiparous, 55 878) participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. After excluding participants with multiple gestations, preconception hypertension, and insufficient data, primiparous and multiparous participants were categorized into five groups according to their preconception carbohydrate-intake quintiles (Q1 and Q5 were the lowest and highest groups, respectively). Multiple logistic regression analysis was performed to identify the effect of preconception carbohydrate intake on early (<34 weeks) and late-onset (≥34 weeks) HDP and the incidence of SGA births. RESULTS: With the middle carbohydrate intake group (Q3) as a reference, the risk for late-onset HDP among multiparous women was higher in the Q5 group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.02-1.69). The incidence of SGA births was higher in the Q1 group among both primiparous (aOR 1.16, 95% CI 1.01-1.33) and multiparous women (aOR 1.16, 95% CI 1.02-1.32). CONCLUSIONS: Excessive carbohydrate intake increases the incidence of HDP in multiparous women, while low-carbohydrate intake increases the incidence of SGA births. New recommendations for preconception carbohydrate intake are required to prevent major HDP-related complications.

Tocolytic treatment and maternal characteristics, obstetric outcomes, and offspring childhood outcomes among births at and after 37 weeks of gestation: the Japan environment and children's study.

PURPOSE: To evaluate differences in maternal characteristics and obstetric and offspring childhood outcomes between births at and after 37 weeks of gestation (referred to as term and post-term births) according to the use of tocolytic treatment. METHODS: Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the Japan Environment and Children's Study (JECS). We compared maternal characteristics, obstetric outcomes, and offspring childhood outcomes between term and post-term births exposed and not exposed to tocolytic treatment. Additionally, multivariable logistic regression models were used to calculate adjusted odds ratios for offspring childhood outcomes with significant between-group differences in the univariable analysis, with term and post-term births without tocolytic agents as the reference group. RESULTS: We observed differences in maternal characteristics and obstetric outcomes between term and post-term births exposed and not exposed to tocolytic treatment. The incidence of offspring childhood developmental disorders showed no significant between-group differences. However, participants exposed to tocolytic agents had higher incidence of offspring childhood allergic disorders. The adjusted odds ratio for any of the offspring childhood allergic disorders in term and post-term births with tocolytic agents was 1.08 (95% confidence interval, 1.03-1.13). CONCLUSION: This study found no significant difference in the incidence of offspring developmental disorders between term and post-term births exposed and not exposed to tocolytic treatment. However, tocolytic treatment was associated with differences in maternal characteristics and obstetric outcomes, along with a marginal increase in the incidence of childhood allergic disorders in offspring.

Gene expression profile and injury sites in mice treated with Shiga toxin 2 and lipopolysaccharide as a Shiga toxin-associated hemolytic uremic syndrome model.

Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS) contribute to the development of hemolytic uremic syndrome (HUS). Mouse models of HUS induced by LPS/Stx2 have been used for elucidating HUS pathophysiology and for therapeutic development. However, the underlying molecular mechanisms and detailed injury sites in this model remain unknown. We analyzed mouse kidneys after LPS/Stx2 administration using microarrays. Decreased urinary osmolality and urinary potassium were observed after LPS/Stx2 administration, suggestive of distal nephron disorders. A total of 1,212 and 1,016 differentially expressed genes were identified in microarrays at 6 h and 72 h after LPS/Stx2 administration, respectively, compared with those in controls. Ingenuity pathway analysis revealed activation of TNFR1/2, iNOS, and IL-6 signaling at both time points, and inhibition of pathways associated with lipid metabolism at 72 h only. The strongly downregulated genes in the 72-h group were expressed in the distal nephrons. In particular, genes associated with distal convoluted tubule (DCT) 2/connecting tubule (CNT) and principal cells of the cortical collecting duct (CCD) were downregulated to a greater extent than those associated with DCT1 and intercalated cells. Stx receptor globotriaosylceramide 3 (Gb3) revealed no colocalization with DCT1-specific PVALB and intercalated cell-specific SLC26A4 but did present colocalization with SLC12A3 (present in both DCT1 and DCT2), and AQP2 in principal cells. Gb3 localization tended to coincide with the segment in which the downregulated genes were present. Thus, the LPS/Stx2-induced kidney injury model represents damage to DCT2/CNT and principal cells in the CCD, based on molecular, biological, and physiological findings.

Robot-Assisted Training as Self-Training for Upper-Limb Hemiplegia in Chronic Stroke: A Randomized Controlled Trial.

BACKGROUND: This study aimed to examine whether robotic self-training improved upper-extremity function versus conventional self-training in mild-to-moderate hemiplegic chronic stroke patients. METHODS: Study design was a multi-center, prospective, randomized, parallel-group study comparing three therapist-guided interventions (1-hour sessions, 3×/wk, 10 weeks). We identified 161 prospective patients with chronic, poststroke, upper-limb hemiplegia treated at participating rehabilitation centers. Patients were enrolled between November 29, 2016, and November 12, 2018 in Japan. A blinded web-based allocation system was used to randomly assign 129 qualifying patients into 3 groups: (1) conventional self-training plus conventional therapy (control, N=42); (2) robotic self-training (ReoGo-J) plus conventional therapy (robotic therapy [RT], N=44); or (3) robotic self-training plus constraint-induced movement therapy (N=43). PRIMARY OUTCOME: Fugl-Meyer Assessment for upper-extremity. SECONDARY OUTCOMES: Motor Activity Log-14 amount of use and quality of movement; Fugl-Meyer Assessment shoulder/elbow/forearm, wrist, finger, and coordination scores; Action Research Arm Test Score; Motricity Index; Modified Ashworth Scale; shoulder, elbow, forearm, wrist, and finger range of motion; and Stroke Impact Scale (the assessors were blinded). Safety outcomes were adverse events. RESULTS: Safety was assessed in 127 patients. An intention-to-treat full analysis set (N=121), and a per-protocol set (N=115) of patients who attended 80% of sessions were assessed. One severe adverse event was recorded, unrelated to the robotic device. No significant differences in Fugl-Meyer Assessment for upper-extremity scores were observed between groups (RT versus control: -1.04 [95% CI, -2.79 to 0.71], P=0.40; RT versus movement therapy: -0.33 [95% CI, -2.02 to 1.36], P=0.90). The RT in the per-protocol set improved significantly in the Fugl-Meyer Assessment for upper-extremity shoulder/elbow/forearm score (RT versus control: -1.46 [95% CI, -2.63 to -0.29]; P=0.037). CONCLUSIONS: Robotic self-training did not improve upper-limb function versus usual self-training, but may be effective combined with conventional therapy in some populations (per-protocol set). REGISTRATION: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000022509.

Gene trapping reveals a new transcriptionally active genome element: The chromosome-specific clustered trap region.

Nearly half of the human genome consists of repetitive sequences such as long interspersed nuclear elements. The relationship between these repeating sequences and diseases has remained unclear. Gene trapping is a useful technique for disrupting a gene and expressing a reporter gene by using the promoter activity of the gene. The analysis of trapped genes revealed a new genome element-the chromosome-specific clustered trap (CSCT) region. For any examined sequence within this region, an equivalent was found using the BLAT of the University of California, Santa Cruz (UCSC) Genome Browser. CSCT13 mapped to chromosome 13 and contained only three genes. To elucidate its in vivo function, the whole CSCT13 region (1.6 Mbp) was deleted using the CRISPR/Cas9 system in mouse embryonic stem cells, and subsequently, a CSCT13 knockout mouse line was established. The rate of homozygotes was significantly lower than expected according to Mendel's laws. In addition, the number of offspring obtained by mating homozygotes was significantly smaller than that obtained by crossing controls. Furthermore, CSCT13 might have an effect on meiotic homologous recombination. This study identifies a transcriptionally active CSCT with an important role in mouse development.

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.

Maternal folic acid supplement use/dietary folate intake from preconception to early pregnancy and neurodevelopment in 2-year-old offspring: the Japan Environment and Children's Study.

We evaluated the association between maternal prenatal folic acid supplementation/dietary folate intake and motor and cognitive development in 2-year-old offspring using data from the Japan Environment and Children's Study database. Neurodevelopment of 2-year-old offspring were evaluated using the Kyoto Scale of Psychological Development 2001. In total, data of 3839 offspring were analysed. For folic acid supplementation, a multiple regression analysis showed that offspring of mothers who started using folic acid supplements before conception had a significantly lower developmental quotient (DQ) in the postural-motor DQ area than offspring of mothers who did not use them at any time throughout their pregnancy (partial regression coefficient (B) -2·596, 95 % CI -4·738, -0·455). Regarding daily dietary folate intake from preconception to early pregnancy, a multiple regression analysis showed that the group with ≥ 200 µg had a significantly higher DQ in the language-social area than the group with <200 µg. The DQ was higher in the ≥ 400 µg group (B 2·532, 95 % CI 0·201, 4·863) than the 200 to <400 µg group (B 1·437, 95 % CI 0·215, 2·660). In conclusion, our study showed that maternal adequate dietary folate intake from preconception to early pregnancy has a beneficial association with verbal cognition development in 2-year-old offspring. On the other hand, mothers who started using folic acid supplements before conception had an inverse association with motor development in 2-year-old offspring. There were no details on the amount of folic acid in the supplements used and frequency of use. Therefore, further studies are required.

Diagnostic reference value of antibody levels measured using enzyme immunoassay for subacute sclerosing panencephalitis.

High measles-specific antibody titers in the cerebrospinal fluid (CSF) have important diagnostic significance for subacute sclerosing panencephalitis (SSPE), a progressive neurological disorder caused by measles virus variants. However, the diagnostic reference value of antibody levels and the usefulness of the CSF/serum ratio measured using enzyme immunoassays (EIAs) for SSPE diagnosis remain unclear. To facilitate SSPE diagnosis using EIAs, measles immunoglobulin G (IgG) titers in the CSF and serum of patients with and without SSPE were measured and their CSF/serum antibody ratios evaluated. Serum and CSF antibody levels were compared among three patients with SSPE (59 paired samples), 37 non-SSPE patients, and 2618 patients of unknown backgrounds. Of the 59 paired samples from three patients with SSPE, 56 paired samples (94.9%) showed CSF measles IgG levels ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, whereas non-SSPE cases showed CSF measles IgG levels <0.1 IU/mL and a CSF/serum ratio <0.03. Of the 2618 CSF samples with unknown backgrounds, 951 showed measurable IgG levels with EIA, with a CSF/serum ratio peak of 0.005-0.02, with a 90th percentile of 0.05. Assuming the SSPE criteria as CSF measles IgG ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, only 20 samples (0.8%) with unknown backgrounds were categorized as having SSPE. Conversely, assuming the non-SSPE criteria as CSF measles IgG <0.1 IU/mL and a CSF/serum ratio <0.03, 2403 samples (92%) with unknown backgrounds were categorized as not having SSPE. In conclusion, high CSF/serum ratios (≥0.05) and high measles CSF IgG levels (≥0.5 IU/mL) may be useful for diagnosing SSPE.