Tsuyoshi Murata

Background: The optimal timing for introducing complementary foods remains under debate. Although guidelines generally recommend introducing solids around 4–6 months of age, evidence linking timing to later food allergy remains inconsistent. We evaluated associations between age at food introduction, caregiver‐reported food‐related allergic symptoms, and allergen‐specific immunoglobulin E (IgE) levels up to 6 years of age. Methods: Using data from the Japan Environment and Children's Study (JECS; 2011–2014), a nationwide birth cohort, we analyzed caregiver‐reported food‐related allergic symptoms in 63,693 children and allergen‐specific IgE levels in a subcohort of 2964 children. Logistic regression assessed associations between timing of food introduction and reported symptoms, and multiple regression evaluated associations with IgE titers. Results: Introduction of certain foods at ≥13 months was associated with higher odds of caregiver‐reported food‐related allergic symptoms, particularly for egg and wheat (egg: aOR 5.69; wheat: aOR 26.69). Some associations were also observed for soy, fish and rice, although estimates were unstable in small subgroups. Children not introduced to egg or milk by 12–13 months had higher egg white– and cow's milk–specific IgE levels at 2, 4, and 6 years. No significant associations were observed for fruit, shellfish, buckwheat, or peanuts. Conclusions: Delayed introduction of selected foods beyond 12–13 months was associated with higher odds of caregiver‐reported food‐related allergic symptoms and, for measured allergens, elevated IgE levels. Given the observational design and questionnaire‐based outcomes, findings should be interpreted cautiously. image

The delta opioid receptor (DOR) is a promising target for treating pain, anxiety, and depression, yet no DOR-based drugs have reached the clinic. Here, we examine how ligands with varying therapeutic properties modulate DOR function. While full agonists rapidly internalize the receptor, partial agonists show a slower rate of internalization, and antagonists increase cell-surface DOR levels. High-resolution structures of ligand-bound DOR-G _i1 complexes, including those with antagonists engaged, reveal key interactions that account for DOR ligand selectivity, potency, and efficacy. Single-molecule fluorescence resonance energy transfer studies show that DOR dynamically samples three distinct states (active, obligate preactive, and inactive), and transition rates are tuned by both ligand efficacy and G protein coupling. The endogenous agonist, met-enkephalin, not only stabilizes the active-state conformation but also catalyzes transitions between the active and inactive states. These results reveal how ligand-specific interactions and receptor dynamics can govern pharmacological profiles and provide a framework for developing DOR-targeted therapeutics.

No consensus has been established for the optimal pre-pregnancy body mass index (BMI) required to reduce the incidence of hypertensive disorders of pregnan

Labor dystocia occurs in 21% of deliveries, increasing the risk of adverse maternal and neonatal outcomes. Pregnant women with obesity have an increased prevalence of labor dystocia due to reduced myometrial contractility. Similarly, in a mouse model, diet-induced obesity (DIO) led to reduced uterine contractility and dystocia, although the underlying mechanisms are not fully understood. Here, we focused on the KATP channel, which links metabolic changes to cellular excitability. KATP channels are activated by a decrease in intracellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio, resulting in cell membrane hyperpolarization and cytoprotection. We show that myometrial smooth muscle cells (MSMCs) isolated from DIO mice had lower mean KATP currents than MSMCs from control-diet (CON) mice. KATP channel blockade by glibenclamide significantly reduced the ex vivo frequency of contractility in uterine tissue from CON mice but not in tissue from DIO mice, suggesting reduced KATP channel activity in DIO mice. Expression of the KATP subunits Kir6.1 and Sur2 was similar between uterine tissues from CON and DIO mice. Analysis of metabolomics data revealed that uterine tissue from DIO mice had a higher ATP/ADP ratio and lower quantities of several phosphatidylinositols than tissue from CON mice. Finally, MSMCs from DIO mice had fewer caveolae and less colocalization of Kir6.1 and caveolin 1 than MSMCs from CON mice. Our results suggest that reduced myometrial KATP channel activity contributes to dampened uterine contractility in obese pregnant mice.

Purpose The association between maternal physique and prevalence of lactational mastitis (LM) in a large study population has not been reported. In this study, we aimed to evaluate the association between pre-pregnancy body mass index (BMI) and LM prevalence. Methods We analyzed data collected from participants enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study conducted between 2011 and 2014. Data from women with singleton births at and after 22 weeks of gestation were analyzed. LM occurrence was identified from medical record transcripts obtained 1-month post-childbirth. Based on the pre-pregnancy BMI, participants were categorized into Group 1 (< 18.5 kg/m²), Group 2 (18.5–24.9 kg/m²), and Group 3 (≥ 25.0 kg/m²). Excluding participants who were not breastfeeding, multivariable logistic regression models were used to evaluate the odds ratios (ORs) for LM in women who were breastfeeding in each BMI category. Group 2 was designated as the reference group. Maternal demographic and socio-economic characteristics were used as confounding factors. Results We analyzed 83,170 participants. The adjusted OR for LM in Group 3 was 0.752 (95% confidence interval, 0.606–0.932). The adjusted OR for LM in Group 1 was not significantly changed. Conclusions High pre-pregnancy BMI was associated with decreased LM prevalence compared with that in the reference group. The maternal preconception physique may be associated with LM prevalence.

Objectives This study aimed to evaluate the association between atopic dermatitis in pregnant women and preterm births, accounting for maternal ritodrine hydrochloride administration status. Methods Data of 83,796 women with singleton pregnancies at and after 22 weeks of gestation (enrolled between 2011 and 2014) were analyzed. These data were obtained from the Japan Environment and Children’s Study. Atopic dermatitis was defined based on self-reported questionnaire responses obtained during the first trimester. The primary outcome measures were preterm births before 37, 32, and 28 weeks of gestation. Using a multivariable logistic regression model, odds ratios for preterm births in pregnant women with atopic dermatitis were calculated, with women without atopic dermatitis included in the reference group. This analysis considered confounding factors and maternal ritodrine hydrochloride administration. Results Among pregnant women with atopic dermatitis, the adjusted odds ratios (95% confidence intervals) for preterm births before 37, 32, and 28 weeks of gestation were 0.89 (0.81–0.98), 0.98 (0.74–1.30), and 0.88 (0.50–1.55), respectively. This trend remained consistent after excluding participants who received ritodrine hydrochloride. Conclusions for practice Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation, even after accounting for the effects of maternal ritodrine hydrochloride administration.