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Objectives: There is growing evidence of ongoing, in utero neurological damage in fetuses with myelomeningocele (MMC). Phospholipase A2 (PLA2) has known neurotoxic properties and is predominantly present in its secretory isoform (sPLA2) in meconium, the passage of which is increased in MMC fetuses. The objective of this study was to determine if amniotic fluid (AF) levels of PLA2 are elevated in a rat model of MMC.Methods: Timed pregnant Sprague-Dawley rats were gavage fed 60 mg/kg/bodyweight retinoic acid (RA) in olive oil at embryonic day 10 (E10). Amniocentesis was performed at multiple gestational time points on MMC fetuses, RA-exposed fetuses without MMC and control fetuses. AF PLA2 levels were analyzed by a fluorescent enzyme activity assay. PLA2 isoforms were determined by measuring activity in the presence of specific inhibitors.Results: There was no difference in AF PLA2 activity between groups on E15. PLA2 activity was significantly increased in MMC fetuses on E17, E19 and E21 (p < 0.001). Secretory PLA2 primarily accounted for the overall greater activity.Conclusions: PLA2 levels are elevated in the AF of fetal rats with MMC and may contribute to ongoing neural injury. This pathway may be a useful drug target to limit ongoing damage and better preserve neurologic function. [ABSTRACT FROM AUTHOR]

Background: Psychosocial stress is a cardiovascular risk factor; however, little is known about whether prenatal psychosocial stressors influence postpartum cardiovascular health. We aimed to examine the associations of multiple measures of prenatal psychosocial stress on maternal blood pressure (BP) in the first 4 years after birth., Methods: Among 225 MADRES cohort (Maternal and Developmental Risks From Environmental and Social Stressors) participants, we examined associations of average prenatal Perceived Stress Scale (PSS), Center for Epidemiological Studies Depression (CES-D) scores, and second-trimester neighborhood social cohesion scores on systolic and diastolic BP collected at annual postpartum study visits (1-4 years) using linear mixed-effects models, adjusted for covariates., Results: Higher prenatal PSS and CES-D scores were associated with greater diastolic BP at 1 year postpartum (0.24 [95% CI, 0.01-0.46] and 0.24 [95% CI, 0.08-0.40] mm Hg per 1-unit higher PSS and CES-D, respectively) and greater systolic BP (0.25 [95% CI, 0.02-0.48] mm Hg per 1-unit higher CES-D). Overall associations of PSS and CES-D with BP were attenuated over the 4-year postpartum period ( P <0.05). Stratified analyses suggested larger associations of PSS and CES-D among US-born participants and participants with normotensive pregnancies. While neighborhood social cohesion was not associated with postpartum BP overall, higher neighborhood social cohesion scores were associated with lower BP at 1 year postpartum among participants with normotensive pregnancies and lower systolic BP among foreign-born Hispanic participants., Conclusions: Higher prenatal perceived stress and depressive symptoms were associated with greater 1-year postpartum BP, whereas neighborhood cohesion was associated with lower 1-year postpartum BP. These results suggest prenatal psychosocial factors may impact cardiovascular health within the first year after birth.

Background: A key driver that leads to age-associated decline and chronic disease is mitochondrial dysfunction. Our previous work revealed strong community interest in the concept of mitochondrial fitness, which led to the development of a video-based science communication intervention to prompt behavior change in adults aged 50 years and older., Objective: This study aimed to conduct formative and summative evaluations of MitoFit, an instructional, biologically based communication intervention aimed at improving physical activity in older adults aged 50 years and older., Methods: In the phase-1 formative evaluation, community-dwelling older adults (N=101) rated the acceptability, appropriateness, and helpfulness of our MitoFit video series, titled "How to Slow Down Aging Through Mitochondrial Fitness." In the phase-2 summative evaluation, a subgroup of phase-1 participants (n=19) participated in a 1-month MitoFit intervention prototype to evaluate the intervention and data collection feasibility., Results: In phase 1, participants (mean age 67.8, SD 8.9 y; 75/100, 75% female) rated the MitoFit videos as acceptable (≥4 out of 5 on a Likert-scale survey; from 97/101, 96% to 100/101, 99%), appropriate (101/101, 100%), and helpful (from 95/101, 94% to 100/101, 99%) to support adaptation and continued work on our novel approach. Previous knowledge of mitochondria ranged from 52% (50/97; What are mitochondria?) to 80% (78/97; What are the primary functions of mitochondria?). In phase 2, participants (mean age 71.4, SD 7.9 y; 13/19, 72% female) scored better than the national average (50) on the Patient-Reported Outcomes Measurement Information System-19 for physical function (57), social activities (55.5), depression (41), fatigue (48.6), and sleep disturbance (49.6) but worse for anxiety (55.3) and pain interference (52.4). Additionally, 95% (18/19) of participants demonstrated MitoFit competencies within 2 attempts (obtaining pulse: 19/19, 100%; calculating maximum and zone 2 heart rate: 18/19, 95%; and demonstration of exercises: 19/19, 100%). At 1 month after instruction, 68% (13/19) had completed a self-initiated daily walking/exercise plan and submitted a daily activity log. A walking pulse was documented by 85% (11/13) of participants. The time needed to walk 1 mile ranged from 17.4 to 27.1 minutes. The number of miles walked in 1 month was documented by 62% (8/13) of participants and ranged from 10 miles to 31 miles. The number of days of strength training ranged from 2 to 31 days/month. Intervention feasibility scores ranged from 89% (17/19; seems easy to follow) to 95% (18/19; seems implementable, possible, and doable). Overall, 79% (15/19) stated an intention to continue the MitoFit intervention. Furthermore, 4 weeks after delivery of the prototype intervention, the percentage of participants doing aerobic activity for regular moderate activity increased from 35% (6/17) to 59% (10/17; P=.03)., Conclusions: MitoFit was enthusiastically embraced and is a cost-effective, scalable, and potentially efficacious intervention to advance with community-dwelling older adults., (©Cathy A Maxwell, Brandon Grubbs, Mary S Dietrich, Jeffrey T Boon, John Dunavan, Kelly J Knickerbocker, Maulik R Patel. Originally published in JMIR Formative Research (https://formative.jmir.org), 13.12.2024.)

Background: Ambient air pollution during pregnancy has been linked with postpartum depression up to 12 months, but few studies have investigated its impact on persistent depression beyond 12 months postpartum. This study aimed to evaluate prenatal ambient air pollution exposure and the risk of persistent depression over 3 years after childbirth and to identify windows of susceptibility., Methods: This study included 361 predominantly low-income Hispanic/Latina participants with full-term pregnancies in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. We estimated daily residential PM 2.5 , PM 10 , NO 2 , and O 3 concentrations throughout 37 gestational weeks using inverse-distance squared spatial interpolation from monitoring data and calculated weekly averaged levels. Depression was assessed by the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale at 12, 24, and 36 months postpartum, with persistent postpartum depression defined as a CES-D score ≥16 at any of these timepoints. We performed robust Poisson log-linear distributed lag models (DLM) via generalized estimating equations (GEE) to estimate the adjusted risk ratio (RR)., Results: Depression was observed in 17.8 %, 17.5 %, and 13.4 % of participants at 12, 24, and 36 months, respectively. We found one IQR increase (3.9 ppb) in prenatal exposure to NO 2 during the identified sensitive window of gestational weeks 13-29 was associated with a cumulative risk ratio of 3.86 (95 % CI: 3.24, 4.59) for persistent depression 1-3 years postpartum. We also found one IQR increase (7.4 μg/m 3 ) in prenatal exposure to PM 10 during gestation weeks 12-28 was associated a cumulative risk ratio of 3.88 (95 % CI: 3.04, 4.96) for persistent depression. No clear sensitive windows were identified for PM 2.5 or O 3 ., Conclusions: Mid-pregnancy PM 10 and NO 2 exposures were associated with nearly 4-fold increased risks of persistent depression after pregnancy, which has critical implications for prevention of perinatal mental health outcomes., Competing Interests: Declaration of competing interest We declare no actual or potential competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy., Methods: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR)., Results: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP., Conclusions: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Personal exposure to fine particulate matter (PM 2.5 ) is impacted by different sources each with different chemical composition. Determining these sources is important for reducing personal exposure and its health risks especially during pregnancy., Objective: Identify main sources and their contributions to the personal PM 2.5 exposure in 213 women in the 3rd trimester of pregnancy in Los Angeles, CA., Methods: We measured 48-hr integrated personal PM 2.5 exposure and analyzed filters for PM 2.5 mass, elemental composition, and optical carbon fractions. We used the EPA Positive Matrix Factorization (PMF) model to resolve and quantify the major sources of personal PM 2.5 exposure. We then investigated bivariate relationships between sources, time-activity patterns, and environmental exposures in activity spaces and residential neighborhoods to further understand sources., Results: Mean personal PM 2.5 mass concentration was 22.3 (SD = 16.6) μg/m 3 . Twenty-five species and PM 2.5 mass were used in PMF with a final R 2 of 0.48. We identified six sources (with major species in profiles and % contribution to PM 2.5 mass) as follows: secondhand smoking (SHS) (brown carbon, environmental tobacco smoke; 65.3%), fuel oil (nickel, vanadium; 11.7%), crustal (aluminum, calcium, silicon; 11.5%), fresh sea salt (sodium, chlorine; 4.7%), aged sea salt (sodium, magnesium, sulfur; 4.3%), and traffic (black carbon, zinc; 2.6%). SHS was significantly greater in apartments compared to houses. Crustal source was correlated with more occupants in the household. Aged sea salt increased with temperature and outdoor ozone, while fresh sea salt was highest on days with westerly winds from the Pacific Ocean. Traffic was positively correlated with ambient NO 2 and traffic-related NO x at residence. Overall, 76.8% of personal PM 2.5 mass came from indoor or personal compared to outdoor sources., Impact: We conducted source apportionment of personal PM 2.5 samples in pregnancy in Los Angeles, CA. Among identified sources, secondhand smoking contributed the most to the personal exposure. In addition, traffic, crustal, fuel oil, fresh and aged sea salt sources were also identified as main sources. Traffic sources contained markers of combustion and non-exhaust wear emissions. Crustal source was correlated with more occupants in the household. Aged sea salt source increased with temperature and outdoor ozone and fresh sea salt source was highest on days with westerly winds from the Pacific Ocean., (© 2024. The Author(s).)

The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range of sugars, ions, and amino acids, are highly susceptible to damage, leading to pathologies necessitating dialysis and kidney transplants. While human pluripotent stem cell-derived kidney organoids are used for modeling renal development, disease, and injury, the formation of proximal nephron cells in these 3D structures is incomplete. Here, we describe how to drive the development of proximal tubule precursors in kidney organoids by following a blueprint of in vivo human nephrogenesis. Transient manipulation of the PI3K signaling pathway activates Notch signaling in the early nephron and drives nephrons toward a proximal precursor state. These "proximal-biased" (PB) organoid nephrons proceed to generate proximal nephron precursor cells. Single-cell transcriptional analyses across the organoid nephron differentiation, comparing control and PB types, confirm the requirement of transient Notch signaling for proximal development. Indicative of functional maturity, PB organoids demonstrate dextran and albumin uptake, akin to in vivo proximal tubules. Moreover, PB organoids are highly sensitive to nephrotoxic agents, display an injury response, and drive expression of HAVCR1 / KIM1 , an early proximal-specific marker of kidney injury. Injured PB organoids show evidence of collapsed tubules, DNA damage, and upregulate the injury-response marker SOX9 . The PB organoid model therefore has functional relevance and potential for modeling mechanisms underpinning nephron injury. These advances improve the use of iPSC-derived kidney organoids as tools to understand developmental nephrology, model disease, test novel therapeutics, and for understanding human renal physiology.

Background: Ambient air pollution has been linked to postpartum depression. However, few studies have investigated the effects of traffic-related NO x on postpartum depression and whether any pregnancy-related factors might increase susceptibility., Objectives: To evaluate the association between traffic-related NO x and postpartum depressive and anxiety symptoms, and effect modification by pregnancy-related hypertension., Methods: This study included 453 predominantly low-income Hispanic/Latina women in the MADRES cohort. Daily traffic-related NO x concentrations by road class were estimated using the California LINE-source dispersion model (CALINE4) at participants' residential locations and averaged across pregnancy. Postpartum depressive and anxiety symptoms were evaluated by a validated questionnaire (Postpartum Distress Measure, PDM) at 1, 3, 6 and 12 months postpartum. Multivariate linear regressions were performed to estimate the associations at each timepoint. Interaction terms were added to the linear models to assess effect modification by hypertensive disorders of pregnancy (HDPs). Repeated measurement analyses were conducted by using mixed effect models., Results: We found prenatal traffic-related NO x was associated with increased PDM scores. Specifically, mothers exposed to an IQR (0.22 ppb) increase in NO x from major roads had 3.78% (95% CI: 0.53-7.14%) and 5.27% (95% CI: 0.33-10.45%) significantly higher 3-month and 12-month PDM scores, respectively. Similarly, in repeated measurement analyses, higher NO x from major roads was associated with 3.06% (95% CI: 0.43-5.76%) significantly higher PDM scores across the first year postpartum. Effect modification by HDPs was observed: higher freeway/highway and total NO x among mothers with HDPs were associated with significantly higher PDM scores at 12 months postpartum compared to those without HDPs., Impact: This study shows that prenatal traffic-related air pollution was associated with postpartum depressive and anxiety symptoms. The study also found novel evidence of greater susceptibility among women with HDPs, which advances the understanding of the relationships between air pollution, maternal cardiometabolic health during pregnancy and postpartum mental health. Our study has potential implications for clinical intervention to mitigate the effects of traffic-related pollution on postpartum mental health disorders. The findings can also offer valuable insights into urban planning strategies concerning the implementation of emission control measures and the creation of green spaces., (© 2024. The Author(s).)