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To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH.Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated.This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]).Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.

Background Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied. Aims To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology. Method The study included 163 children (53.4% girls), longitudinally tracked (ages 2–5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed. Results A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support. Conclusions Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.

Maternal postpartum depression (PPD) is a well-established risk factor for psychological problems in children; however, little is known about the sustained impact of persistent PPD patterns and severity on these problems in children.Data were obtained from mothers (N = 714) and children (N = 768) from the Hamamatsu Birth Cohort for Mothers and Children. Maternal depression was measured using the Edinburgh Postpartum Depression Scale at 2, 4, 10 weeks and 10 months postpartum. Children's internalizing and externalizing problems were assessed using the Strengths and Difficulties Questionnaire at 6 years and 8-9 years old. Mothers were divided into 4 groups based on the trajectory of their PPD persistence: "No PPD," "Transient PPD," "Worsening PPD" and "Persistent PPD." Linear regression analysis was used to examine the association of PPD persistence and severity with children's internalizing and externalizing problems."Persistent PPD" was significantly associated with children's internalizing problems at 6 years old (Coefficient [95%CI] = 2.74 [1.30-4.19], P .001), but no association was found at 8-9 years old. No associations were found between PPD severity and children's internalizing and externalizing problems in either age category."Persistent PPD" and "Worsening PPD" groups had a relatively small sample size. The mothers' depression statuses were not ascertained simultaneously with the children's behavioral assessments. There was no information regarding the mothers' treatment for PPD.PPD persistence negatively affected children's internalizing problems but was not long-lasting. Future studies are needed to identify protective factors against PPD persistence in children's psychological problems.

The current study investigated 304 children from a longitudinal project (the Stress in Pregnancy (SIP) Study) who were exposed and unexposed to Superstorm Sandy (“Sandy”) in utero. They were prospectively followed from 2 to 6 years of age and their clinical and adaptive behaviors were assessed annually. Using a hierarchical linear model, the study found that in utero Sandy exposure was associated with greater clinical (anxiety, depression, and somatization) and lower adaptive behaviors (social skills and functional communication) at age 2 years. However, the trajectories were notably different between the two groups. Anxiety increased more rapidly among the exposed than unexposed group at ages 2–4, and depression increased only among the exposed. In contrast, social skills and functional communication were lower in exposed compared to unexposed children at age 2, but quickly increased and exceeded the capacities of unexposed children by age 3. The findings confirm that prenatal Sandy exposure is not only associated with an increase in anxiety, depression, and somatization in offspring, but also with greater adaptive skills as the children got older. Our study demonstrates that while children who have experienced stress in utero demonstrate elevated suboptimal clinical behaviors related to affective disorders, they nevertheless have the potential to learn adaptive skills.

A small molecule-responsive self-cleaving ribozyme (aptazyme) embedded in the untranslated region of an mRNA functions as a riboswitch that allows chemical regulation of gene expression in mammalian cells. Aptazymes are engineered by fusing a self-cleaving ribozyme with an RNA aptamer that recognizes a small molecule so that the ribozyme is either activated or inhibited in the presence of the small molecule. However, the variety of aptamers, ribozymes, and aptazyme design strategies suitable for mammalian riboswitch applications is still limited. This work focuses on a new ribozyme scaffold for engineering aptazymes and riboswitches that function in mammalian cells. We investigated circularly permuted variants of the pistol ribozyme class (CPP) as a synthetic ribozyme scaffold for mammalian riboswitch applications. Through semirational design and high-throughput screening, we designed guanine and tetracycline activated riboswitches based on three distinct aptazyme architectures, resulting in riboswitches with ON/OFF ratios as high as 8.6. Our work adds CPP to the limited ribozyme scaffold toolbox for mammalian synthetic biology applications and highlights the opportunities in exploring ribozymes beyond natural motifs.

Growing evidence shows an association between in utero exposure to natural disasters and child behavioral problems, but we still know little about the development of specific psychopathology in preschool-aged children.Preschool children (n = 163, mean age = 3.19, 85.5% racial and ethnic minorities) and their parents (n = 151) were evaluated annually at ages 2-5 to assess the emergence of psychopathology using the Preschool Age Psychopathological Assessment (PAPA), a parent-report structured diagnostic interview developed for preschool-age children. Sixty-six (40.5%) children were exposed to Sandy Storm (SS) in utero and 97 (59.5%) were not. Survival analysis evaluated patterns of onset and estimated cumulative risks of psychopathology among exposed and unexposed children, in total and by sex. Analyses were controlled for the severity of objective and subjective SS-related stress, concurrent family stress, and demographic and psychosocial confounders, such as maternal age, race, SES, maternal substance use, and normative prenatal stress.Exposure to SS in utero was associated with a substantial increase in depressive disorders (Hazard Ratio (HR) = 16.9, p = .030), anxiety disorders (HR = 5.1, p .0001), and attention-deficit/disruptive behavioral disorders (HR = 3.4, p = .02). Diagnostic rates were elevated for generalized anxiety disorder (GAD; HR = 8.5, p = .004), attention-deficit/hyperactivity disorder (ADHD; HR = 5.5, p = .01), oppositional-defiant disorder (ODD; HR = 3.8, p = .05), and separation-anxiety disorder (SAD; HR = 3.5, p = .001). Males had distinctively elevated risks for attention-deficit/disruptive behavioral disorders (HR = 7.8, p = .02), including ADHD, CD, and ODD, whereas females had elevated risks for anxiety disorders (HR = 10.0, p .0001), phobia (HR = 2.8, p = .02) and depressive disorders (HR = 30.0, p = .03), including SAD, GAD, and dysthymia.The findings demonstrate that in utero exposure to a major weather-related disaster (SS) was associated with increased risk for psychopathology in children and provided evidence of distinct psychopathological outcomes as a function of sex. More attention is needed to understand specific parent, child, and environmental factors which account for this increased risk, and to develop mitigation strategies.

【要旨】超高齢社会に対応するための制度改革が頻回に行われ，制度設計にアドボケーターとして看護職の関わりが求められていることから，看護基礎教育において政策の基本を体系的に学ぶことが必要と考え，政策教育プログラム開発に関する研究を行った。 1 年目の研究では看護に関連した政策に現に取り組んでいる 政策企画者等を対象に面接調査を行い，政策教育において獲得すべきコンピテンシー77 項目を抽出し，これを日本公共政策学会の参照基準をもとに 8 つのカテゴリーに分類した。この結果を参照基準と比較すると，参照基準の「政策の働きに関する基本的理解」などの項目は少なかったが，「政策問題を主体的に考える力」の項目は非常に豊富であった。このことは対象者が政策の実践者であったことが影響しており，また，看護教育に対して政策決定に関する“知識”に力点を置くよりも，看護現場の課題を解決するための能力獲得に期待がされていることが明らかとなった。, With frequent revisions in the medical-care system in response to the aging society, nurses are required to be involved in system design as advocators. This suggests the necessity for nursing students to systematically learn the basics of policy studies in basic nursing education. Given this background, we conducted research into the development of a nursing education program related to policy studies. In the first year of the research, we conducted an interview survey with policy planners who worked on policies related to nursing. From the interview data, we extracted 77 items of competencies to be acquired through the education program, and classified the items into 8 categories based on the academic standards of the Public Policy Studies Association, Japan (PPSAJ). Comparing the results in this study with the items of the academic standards, there were fewer items related to the “Basic understanding of the functions of policy” than those in the standards, but there were many items related to the “Competencies to think independently about policy issues”. These results may be because the participants in the interviews were policy practitioners. The findings suggest that it is important for nursing education to place more emphasis on competencies needed to solve problems in nursing settings than on knowledge about policy making.

ImportanceWhether the association between higher screen time in infancy and later suboptimal neurodevelopment can be mitigated by frequency of outdoor play is unknown.ObjectiveTo investigate whether higher screen time at age 2 years is associated with neurodevelopmental outcomes at age 4 years and whether this association is mediated by frequency of outdoor play at age 2 years 8 months.Design, Setting, and ParticipantsParticipants were a subsample of the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study, N = 1258). Children were born between December 2007 and March 2012 and followed up from 1 year 6 months to 4 years. The analysis was conducted from April 2021 to June 2022.ExposuresScreen time longer than 1 hour a day at age 2 years was coded as higher screen time.Main Outcomes and MeasuresStandardized scores for communication, daily living skills, and socialization domains of the Vineland Adaptive Behavior Scale, second edition, at age 4 years were used (mean [SD], 100 [15]). The mediating factor was frequency of outdoor play at age 2 years 8 months, with 6 or 7 days per week coded as frequent outdoor play.ResultsOf 885 participants, 445 children (50%) were female; mean (SD) screen time per day was 2.6 (2.0) hours. Causal mediation analyses revealed that higher screen time at age 2 years was associated with lower scores in communication at age 4 years (nonstandardized coefficient b = −2.32; 95% CI, −4.03 to −0.60), but the association was not mediated by frequency of outdoor play. Higher screen time was also associated with lower scores in daily living skills (b = −1.76; 95% CI, −3.21 to −0.31); 18% of this association was mediated by frequency of outdoor play. Frequency of outdoor play was associated with socialization (b = 2.73; 95% CI, 1.06 to 4.39), whereas higher screen time was not (b = −1.34; 95% CI, −3.05 to 0.36).Conclusions and RelevanceHigher screen time at age 2 years was directly associated with poorer communication at age 4 years. It was also associated with daily living skills, but frequency of outdoor play at age 2 years 8 months alleviated it, suggesting outdoor play mitigated the association between higher screen time and suboptimal neurodevelopment. Future research should specify the nature of the associations and intervention measures, enabling targeted interventions that reduce the potential risk in screen time.

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold P = 0.002) and inattention domain (e.g., P-value threshold P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

Purpose To evaluate the usefulness of the retinal sensitivity in branch retinal vein occlusion (BVO) with macular edema (ME) following the anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) measurements were carried out in 20 patients with BVO with ME, at baseline and 1 month after the anti-VEGF treatment. The relationships among BCVA, mean retinal sensitivity (MS), macular volume (MV), central retinal thickness (CRT), integrity of ellipsoid zone (EZ), mean retinal sensitivity in the most affected quadrant (qMS), and macular volume in the most affected quadrant (qMV) were investigated. In addition, the relationships among the change in BCVA at 1 month (ΔBCVA1m), mean sensitivity in the most affected quadrant at 1 month (ΔqMS1m), MV in the most affected quadrant at 1 month (ΔqMV1m), and CRT at 1 month (ΔCRT1m) were analyzed. The optimal model for BCVA at 3 months after the treatment (BCVA3m) was identified. Results There was not a significant difference in BCVA (paired Wilcoxon test, p = 0.058) between at baseline and after the treatment, but there were significant differences in MS, MV, CRT, qMS, and qMV (p Conclusion Retinal sensitivity was related to retinal structure, whereas this was not the case with BCVA. In addition, retinal sensitivity was useful to predict BCVA after anti-VEGF therapy.

Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory.A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits.Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time.GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

Little is known about the trajectory patterns and sex differences in adaptive behaviors in the general population. We examined the trajectory classes of adaptive behaviors using a representative sample and examined whether the class structure and trajectory patterns differed between females and males. We further explored sex differences in neurodevelopmental traits in each latent class. Participants (n = 994) were children in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study)—a prospective birth cohort study. Adaptive behaviors in each domain of communication, daily living skills, and socialization were evaluated at five time points when participants were 2.7, 3.5, 4.5, 6, and 9 years old using the Vineland Adaptive Behavior Scales–Second Edition. Parallel process multigroup latent class growth analysis extracted sex-specific trajectory classes. Neurodevelopmental traits of children at age 9, autistic traits, attention deficit hyperactivity disorder (ADHD) traits, and cognitive ability were examined for females and males in each identified class. A 4-class model demonstrated the best fit. Moreover, a 4-class model that allowed for differences in class probabilities and means of growth parameters between females and males provided a better fit than a model assuming no sex differences. In the communication domain, females scored higher than their male counterparts in all four classes. In the daily living skills and socialization domains, the two higher adaptive classes (Class 1: females, 18.6%; males, 17.8%; Class 2: females, 48.8%; males, 49.8%) had similar trajectories for males and females, whereas in the two lower adaptive behavior classes (Class 3: females, 27.5%; males, 29.4%; Class 4: females, 5.1%; males, 3.0%), females had higher adaptive scores than their male counterparts. In Class 4, females were more likely to have autistic and ADHD traits exceeding the cutoffs, while males were more likely to have below-average IQ. Different trajectories in females and males suggest that adaptive skills may require adjustment based on the sex of the child, when standardizing scores, in order to achieve better early detection of skill impairment.

IntroductionAccumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet.MethodsThis study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8–9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB).ResultsUmbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081–1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206–2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000–1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant.DiscussionThe present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children’s risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (β = − 0.34; p = 0.01), with a marginally significant interaction with the child’s age (β = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (β = − 0.26, 95% CI − 0.51, 0; p = 0.05), with a significant interaction with the child’s age (β = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls.

While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Here, we assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in utero environment reflected in the placental transcriptome. Children (∼3 to 6 y) were assessed for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing. Hair hormone analysis revealed increased cortisol levels in mCB children. In addition, mCB was associated with greater anxiety, aggression, and hyperactivity. Children with mCB also showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone. In the placenta, there was reduced expression of many genes involved in immune system function including type I interferon, neutrophil, and cytokine-signaling pathways. Finally, several of these mCB-linked immune genes organized into coexpression networks that correlated with child anxiety and hyperactivity. Overall, our findings reveal a relationship between mCB and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood.

Maternal psychosocial stress during pregnancy (MPSP) is a known contributor to maladaptive neurobehavioral development of the offspring; however, the underlying molecular mechanisms linking MPSP with childhood outcome remain largely unknown. Transcriptome-wide gene expression data were generated using RNA-seq from placenta samples collected in a multi-ethnic urban birth cohort in New York City (n = 129). Weighted gene co-expression network analysis (WGCNA) was used to characterize placental co-expression modules, which were then evaluated for their associations with MPSP and infant temperament. WGCNA revealed 16 gene coexpression modules. One module, enriched for regulation of chromosome organization/gene expression, was positively associated with MPSP and negatively associated with Regulatory Capacity (REG), a component of infant temperament. Two other modules, enriched for cotranslational protein targeting and cell cycle regulation, respectively, displayed negative associations with MPSP and positive associations with REG. A module enriched with oxidative phosphorylation/mitochondrial translation was positively associated with REG. These findings support the notion that the placenta provides a functional in utero link between MPSP and infant temperament, possibly through transcriptional regulation of placental gene expression.

Background: This study investigated COVID-19 related psychological distress among expectant and new mothers, with and without infection, in metropolitan New York. It also examined the trajectories of participants' distress during pregnancy and postpartum, and the moderating effect of socioeconomic status (SES). Methods: An online survey was conducted April through June 2020 among expectant and new mothers with infants (Results: We found elevated anxiety and depression among infected compared to uninfected women. Similarly, infected, compared to uninfected women, had elevated risk for suicidal thoughts (quite often, AOR=3.97, sometimes AOR=13.2), and for substance use [alcohol (AOR=3.30); tobacco (AOR=4.54); cannabis (AOR=7.01); heroin (AOR=7.09); cocaine (AOR=10.05)]. Differences in trajectories of distress across pregnancy between the two groups were significant. Among infected women, distress was consistently high throughout. Among uninfected women, it started low and intensified toward the end of pregnancy. SES further moderated the impact of infection on distress. During earlier trimesters, infected/low SES women had greatest, and uninfected/high SES women had lowest, levels of distress. Their trajectories converged nearing childbirth.Conclusions: New and expectant mothers, especially those infected, have suffered substantial psychological distress due to the pandemic. Moreover, SES moderated the trajectory of distress. Infected women who also had low SES experienced the highest distress levels among all groups. Mitigating strategies are imperative to alleviate this distress.

This chapter describes a screening strategy to engineer synthetic riboswitches that can chemically regulate gene expression in mammalian cells. Riboswitch libraries are constructed by randomizing the key nucleotides that couple the molecular recognition function of an aptamer with the self-cleavage activity of a ribozyme. The allosteric ribozyme (aptazyme) candidates are cloned in the 3' untranslated region (UTR) of a reporter gene mRNA. The plasmid-encoded riboswitch candidates are transfected into a mammalian cell line to screen for the desired riboswitch function. Furthermore, multiple aptazymes can be cloned into the 3' UTR of a desired gene to obtain a logic gate response to multiple chemical signals. This screening strategy complements other methods to engineer robust mammalian riboswitches to control gene expression.

To investigate retinal sensitivity in eyes with angioid streaks (AS). This study was a retrospective observational case series. A total of 13 eyes from 9 patients with AS underwent ophthalmologic examination, including fundus autofluorescence (FAF), spectral domain optical tomography (SD-OCT), and microperimetry. Retinal pigment epithelium (RPE) atrophy was assessed using FAF. Outer retinal atrophy, more specifically, disruption of the ellipsoid zone, was evaluated using SD-OCT images. The association between retinal sensitivity, RPE atrophy or outer retinal atrophy, and patient demographic characteristics or ophthalmologic findings were investigated. The mean area of outer retinal atrophy was 14.5 ± 12.9 mm2, significantly larger than the mean area of RPE atrophy (9.0 ± 9.0 mm2; P = 0.0028). The average retinal sensitivity in the area of RPE atrophy was 2.4 ± 5.6 dB, that in the area of outer retinal atrophy outside RPE atrophy was 14.6 ± 7.5 dB, and that in the area without any atrophy was 25.6 ± 5.1 dB. Reticular pseudodrusen (RPD) was observed in 5 eyes. Eyes with RPD showed a greater extent of both outer retinal atrophy and RPE atrophy than those without RPD and a greater decrease in mean retinal sensitivity. In eyes with AS, especially in those with RPD, large areas of outer retinal atrophy and RPE atrophy were observed, and the retinal sensitivity in the areas was correspondingly decreased.

Many non-coding and regulatory RNA elements have evolved to exploit transient or metastable structures that emerge during transcription to control complex folding pathways or to encode dynamic functions. However, efforts to engineer synthetic RNA devices have mostly focused on the thermodynamically stable structures. Consequently, significant challenges and opportunities exist in engineering functional RNAs that explicitly take advantage of cotranscriptionally generated transient or metastable structures. In this work, we designed a short RNA sequence that adopts a robust metastable structure when transcribed by an RNA polymerase. Although the metastable structure persists for hours at low temperature, it refolds almost completely into the thermodynamically stable structure upon heat denaturation followed by cooling. The synthetic RNA was also equipped with the Broccoli aptamer so that it can bind its ligand and become fluorescent only in the thermodynamically stable structure. We further demonstrated that the relaxation to the thermodynamically stable and fluorescent structure can be catalyzed by a short trigger RNA in a sequence-specific manner. Finally, the RNA architecture was redesigned to sense and respond to microRNA sequences. In summary, we designed RNA nanomachines that can detect an RNA sequence, amplify signal and produce an optical output, all encoded in a single RNA transcript, self-powered by a metastable structure.

Little is known about whether a mother’s psychological state during pregnancy influences her offspring’s microbiome. This study examined whether maternal anxiety, depression, and stress during pregnancy is associated with the diversity of meconium microbiome, the first internal discharge, in 75 newborns from an existing birth cohort study. The meconium microbiome was profiled using multi-barcode16S rRNA sequencing at V3-V4 hyper-variable region followed by taxonomic assignment to the green gene 16S references at 97% similarity and diversity analysis at the genus level. Results showed that the meconium contained diversified microbiota, and greater pregnancy-related anxiety was significantly associated with a less diverse meconium microbiota community (p-value=0.001). At the specific taxa level, greater pregnancy-related anxiety was correlated with a lower level of the Enterococcaceae family (p-value=2e-4, Spearman rho=−0.43). These findings support a significant role of prenatal maternal mood in the early life bacteria colonization of their offspring.