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PurposeThis study aims to characterize the June 2020 COVID-19 outbreak at San Quentin California State Prison and to describe what made San Quentin so vulnerable to uncontrolled transmission.Design/methodology/approachSince its onset, the COVID-19 pandemic has exposed and exacerbated the profound health harms of carceral settings, such that nearly half of state prisons reported COVID-19 infection rates that were four or more times (and up to 15 times) the rate found in the state's general population. Thus, addressing the public health crises and inequities of carceral settings during a respiratory pandemic requires analyzing the myriad factors shaping them. In this study, we reported observations and findings from environmental risk assessments during visits to San Quentin California State Prison. We complemented our assessments with analyses of administrative data.FindingsFor future respiratory pathogens that cannot be prevented with effective vaccines, this study argues that outbreaks will no doubt occur again without robust implementation of additional levels of preparedness - improved ventilation, air filtration, decarceration with emergency evacuation planning - alongside addressing the vulnerabilities of carceral settings themselves.Originality/valueThis study addresses two critical aspects that are insufficiently covered in the literature: how to prepare processes to safely implement emergency epidemic measures when needed, such as potential evacuation, and how to address unique challenges throughout an evolving pandemic for each carceral setting.

Abstract Background The rate and magnitude of skeletal muscle wasting after severe spinal cord injury (SCI) exceeds most other disuse conditions. Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post‐SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes. Methods Four‐month‐old Sprague–Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1 week, 2 weeks, 1 month and 3 months post‐surgery (n = 6–7 per group per timepoint). RNA was extracted from muscles for bulk RNA‐sequencing analysis (n = 3–5 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age‐matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles. Results SCI produced immediate and persistent hindlimb paralysis, with Basso–Beattie–Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25–50% lower soleus mass and myofiber atrophy versus SHAM (P 50% higher ECM areas and hydroxyproline levels in SCI muscles (P

Abstract Background and aim Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium. Methods We included 1,081 birth parent–child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8–9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. Results The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant. Conclusions In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8–9 years, though some adverse associations were observed among girls.

Background Ambient fine particulate matter (PM2.5) exposure adversely impacts child airway health; however, research on prenatal PM2.5 exposure, and child lung function is limited. We investigated these associations in the ECHO-PATHWAYS Consortium, focusing on the role of exposure timing during different phases of fetal lung development.Methods We included 675 children in the CANDLE cohort born between 2007 and 2011 in Memphis, TN, USA. Prenatal exposure to ambient PM2.5 was estimated using a spatiotemporal model based on maternal residential history and averaged over established prenatal periods of lung development. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured by spirometry at age 8–9 years. We used linear regression and Bayesian Distributed Lag Interaction Models (BDLIM) to estimate associations between exposure and lung function z-scores, adjusting for maternal/child characteristics, prenatal/postnatal tobacco exposure, and birth year/season, and evaluating effect modification by child sex and allergic sensitization.Results The average ambient concentration of PM2.5 during pregnancy was 11.1 µg/m3 (standard deviation:1.0 µg/m3). In the adjusted linear regression and BDLIM models, adverse, but not statistically significant, associations were observed between exposure during the pseudoglandular (5–16 weeks of gestation) and saccular (24–36 weeks) phases of lung development and FEV1 and FVC. The strongest association was between a 2 μg/m3 higher concentration of PM2.5 during the saccular phase and FEV1 z-score (−0.176, 95% Confidence Interval [CI]: −0.361, 0.010). The FEV1/FVC ratio was not associated with PM2.5 in any exposure window. No effect modification by child sex or allergic sensitization was observed.Conclusions We did not find strong evidence of associations between prenatal ambient PM2.5 exposure and child lung function in a large, well-characterized study sample. However, there was a suggested adverse association between FEV1 and exposure during late pregnancy. The saccular phase of lung development might be an important window for exposure to PM2.5.

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants originating from petrogenic and pyrogenic sources. PAH compounds can cross the placenta, and prenatal PAH exposure is linked to adverse infant and childhood health outcomes.ObjectiveIn this first human transcriptomic assessment of PAHs in the placenta, we examined associations between prenatal PAH exposure and placental gene expression to gain insight into mechanisms by which PAHs may disrupt placental function.MethodsThe ECHO PATHWAYS Consortium quantified prenatal PAH exposure and the placental transcriptome from 629 pregnant participants enrolled in the CANDLE study. Concentrations of 12 monohydroxy-PAH (OH-PAH) metabolites were measured in mid-pregnancy urine using high performance liquid chromatography tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate covariate-adjusted associations between maternal urinary OH-PAHs and placental gene expression. We performed sex-stratified analyses to evaluate whether associations varied by fetal sex. Selected PAH/gene expression analyses were validated by treating HTR-8/SVneo cells with phenanthrene, and quantifying expression via qPCR.ResultsUrinary concentrations of 6 OH-PAHs were associated with placental expression of 8 genes. Three biological pathways were associated with 4 OH-PAHs. Placental expression of SGF29 and TRIP13 as well as the vitamin digestion and absorption pathway were positively associated with multiple metabolites. HTR-8/SVneo cells treated with phenanthrene also exhibited 23 % increased TRIP13 expression compared to vehicle controls (p = 0.04). Fetal sex may modify the relationship between prenatal OH-PAHs and placental gene expression, as more associations were identified in females than males (45 vs 28 associations).DiscussionOur study highlights novel genes whose placental expression may be disrupted by OH-PAHs. Increased expression of DNA damage repair gene TRIP13 may represent a response to double-stranded DNA breaks. Increased expression of genes involved in vitamin digestion and metabolism may reflect dietary exposures or represent a compensatory mechanism to combat damage related to OH-PAH toxicity. Further work is needed to study the role of these genes in placental function and their links to perinatal outcomes and lifelong health.

BackgroundPrenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited.ObjectivesWe estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status.MethodsWe pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother-child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4-6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors.ResultsThe sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemale = 1.29 [95 % CI: 1.09, 1.52], RRmale = 0.95 [95 % CI: 0.79, 1.13]; pinteraction = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma.DiscussionThis analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects.

BackgroundPeople incarcerated in US prisons have been disproportionately harmed by the COVID-19 pandemic. That prisons are such efficient superspreading environments can be attributed to several known factors: small, communal facilities where people are confined for prolonged periods of time; poor ventilation; a lack of non-punitive areas for quarantine/medical isolation; and staggeringly high numbers of people experiencing incarceration, among others. While health organizations have issued guidance on preventing and mitigating COVID-19 infection in carceral settings, little is known about if, when, and how recommendations have been implemented. We examined factors contributing to containment of one of the first California prison COVID-19 outbreaks and remaining vulnerabilities using an adapted multi-level determinants framework to systematically assess infectious disease risk in carceral settings.MethodsCase study employing administrative data; observation; and informal discussions with: people incarcerated at the prison, staff, and county public health officials.ResultsOutbreak mitigation efforts were characterized by pre-planning (e.g., designation of ventilated, single-occupancy quarantine) and a quickly mobilized inter-institutional response that facilitated systematic, voluntary rapid testing. However, several systemic- and institutional-level vulnerabilities were unaddressed hindering efforts and posing significant risk for future outbreaks, including insufficient decarceration, continued inter-facility transfers, incomplete staff cohorting, and incompatibility between built environment features (e.g., dense living conditions) and public health recommendations.ConclusionsOur adapted framework facilitates systematically assessing prison-based infectious disease outbreaks and multi-level interventions. We find implementing some recommended public health strategies may have contributed to outbreak containment. However, even with a rapidly mobilized, inter-institutional response, failure to decarcerate created an overreliance on chance conditions. This left the facility vulnerable to future catastrophic outbreaks and may render standard public health strategies - including the introduction of effective vaccines - insufficient to prevent or contain those outbreaks.

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are ubiquitous chemicals with mechanisms of toxicity that include endocrine disruption. We examined associations of prenatal urinary PAH with spontaneous preterm birth (PTB) and gestational age (GA) at birth. We also assessed whether infant sex modifies the association of PAH exposure with spontaneous PTB and GA at birth.MethodsParticipants included 1,677 non-smoking women from three cohorts (CANDLE, TIDES, and GAPPS) in the ECHO PATHWAYS Consortium. Twelve monohydroxylated-PAHs were measured in second trimester maternal urine. Seven metabolites with >60% overall detection were included in analyses: 1-hydroxynaphthalene [1-OH-NAP], 2-hydroxynaphthalene [2-OH-NAP], 2-hydroxyphenanthrene [2-OH-PHEN], 3-hydroxyphenanthrene [3-OH-PHEN], 1/9-hydroxyphenanthrene [1/9-OH-PHEN], 2/3/9-hydroxyfluorene [2/3/9-OH-FLUO], and 1-hydroxypyrene [1-OH-PYR]. Logistic and linear regression models were fit for spontaneous PTB and GA among births ≥34 weeks, respectively, with log10-transformed OH-PAH concentrations as the exposure, adjusted for specific gravity and suspected confounders. Effect modification by infant sex was assessed using interaction terms and marginal estimates.ResultsPercent detection was highest for 2-OH-NAP (99.8%) and lowest for 1-OH-PYR (65.2%). Prevalence of spontaneous PTB was 5.5% (N = 92). Ten-fold higher 2-OH-NAP exposure was associated with 1.60-day (95% CI: -2.92, -0.28) earlier GA at birth. Remaining associations in the pooled population were null. Among females, we observed significant inverse associations between 1-OH-PYR and PTB (OR: 2.65 [95% CI: 1.39, 5.05]); and 2-OH-NAP with GA: -2.46 days [95% CI: -4.15, -0.77]). Among males, we observed an inverse association between 2/3/9-OH-FLUO and PTB (OR = 0.40 [95% CI: 0.17,0.98]). ORs for PTB were higher among females than males for 2-OH-PHEN (p = 0.02) and 1-OH-PYR (p = 0.02).DiscussionWe observed inverse associations of 2-OH-NAP exposure with GA and null associations of remaining OH-PAHs with GA and PTB. Females may be more susceptible to spontaneous PTB or shorter GA following prenatal exposure to some OH-PAHs. This study is the first to assess sex-specific OH-PAH toxicity in relation to spontaneous PTB and GA.

A multimorbidity-focused approach may reflect common etiologic mechanisms and lead to better targeting of etiologic agents for broadly impactful public health interventions. Our aim was to identify clusters of chronic obesity-related, neurodevelopmental, and respiratory outcomes in children, and to examine associations between cluster membership and widely prevalent chemical exposures to demonstrate our epidemiologic approach. Early to middle childhood outcome data collected 2011–2022 for 1092 children were harmonized across the ECHO-PATHWAYS consortium of 3 prospective pregnancy cohorts in six U.S. cities. 15 outcomes included age 4–9 BMI, cognitive and behavioral assessment scores, speech problems, and learning disabilities, asthma, wheeze, and rhinitis. To form generalizable clusters across study sites, we performed k-means clustering on scaled residuals of each variable regressed on study site. Outcomes and demographic variables were summarized between resulting clusters. Logistic weighted quantile sum regressions with permutation test p-values associated odds of cluster membership with a mixture of 15 prenatal urinary phthalate metabolites in full-sample and sex-stratified models. Three clusters emerged, including a healthier Cluster 1 (n = 734) with low morbidity across outcomes; Cluster 2 (n = 192) with low IQ and higher levels of all outcomes, especially 0.4–1.8-standard deviation higher mean neurobehavioral outcomes; and Cluster 3 (n = 179) with the highest asthma (92 %), wheeze (53 %), and rhinitis (57 %) frequencies. We observed a significant positive, male-specific stratified association (odds ratio = 1.6; p = 0.01) between a phthalate mixture with high weights for MEP and MHPP and odds of membership in Cluster 3 versus Cluster 1. These results identified subpopulations of children with co-occurring elevated levels of BMI, neurodevelopmental, and respiratory outcomes that may reflect shared etiologic pathways. The observed association between phthalates and respiratory outcome cluster membership could inform policy efforts towards children with respiratory disease. Similar cluster-based epidemiology may identify environmental factors that impact multi-outcome prevalence and efficiently direct public policy efforts.

Abstract Cell autonomous behaviors such as migration and orchestration of cell polarity programs are required for physiological tissue formation. Micropatterns are cell-adhesive shapes that confine cell(s) to a user defined geometry. This biophysical confinement allows researchers to standardize the cell shape, and in doing so, stereotype organelle and cytoskeletal systems that can have an arbitrary organization. Thus, micropatterning can be a powerful tool in interrogation of polarity programs by enforcing a homogenous cell shape and cytoskeletal organization. A major drawback of this approach is the equipment and reagent costs associated with fabrication. Here, we provide a characterization of a compound called Lipidure (2-Methacryloyloxy ethyl phosphorylcholine) that is up to 40X less expensive than other cell repulsive coating agents. We found that Lipidure is an effective cell-repulsive agent for photolithography-based micropattern fabrication. Our results demonstrate that Lipidure is sensitive to deep UV irradiation for photolithography masking, stable in both benchtop and aqueous environments, non-toxic in prolonged culture, and effective at constraining cell geometry for quantification of cytoskeletal systems.

BackgroundAnimal and epidemiological studies suggest that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may negatively impact toddler neurodevelopment.MethodsWe investigated this association in 835 mother-child pairs from CANDLE, a diverse pregnancy cohort in the mid-South region of the U.S. PAH metabolite concentrations were measured in mid-pregnancy maternal urine. Cognitive and Language composite scores at ages 2 and 3 years were derived from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3). Behavior Problem and Competence scores at age 2 were derived from the Brief Infant and Toddler Social Emotional Assessment (BITSEA). We used multivariate linear or Poisson regression to estimate associations with continuous scores and relative risks (RR) of neurodevelopment delay or behavior problems per 2-fold increase in PAH, adjusted for maternal health, nutrition, and socioeconomic status. Secondary analyses investigated associations with PAH mixture using Weighted Quantile Sum Regression (WQS) with a permutation test extension.Results1- hydroxypyrene was associated with elevated relative risk for Neurodevelopmental Delay at age 2 (RR = 1.20, 95% CI: 1.03,1.39). Contrary to hypotheses, 1-hydroxynaphthalene was associated with lower risk for Behavior Problems at age 2 (RR = 0.90, 95% CI: 0.83,0.98), and combined 1- and 9-hydroxyphenanthrene was associated with 0.52-point higher (95% CI: 0.11,0.93) Cognitive score at age 3. For PAH mixtures, a quintile increase in hydroxy-PAH mixture was associated with lower Language score at age 2 (βwqs = -1.59; 95% CI: -2.84, -0.34; ppermutation = 0.07) and higher Cognitive score at age 3 (βwqs = 0.96; 95% CI: 0.11, 1.82; ppermutation = 0.05). All other estimates were consistent with null associations.ConclusionIn this large southern U.S. population we observed some support for adverse associations between PAHs and neurodevelopment.

BackgroundPhthalates are commonly used endocrine-disrupting chemicals that are ubiquitous in the general population. Prenatal phthalate exposure may alter placental physiology and fetal development, leading to adverse perinatal and childhood health outcomes.ObjectiveWe examined associations between prenatal phthalate exposure in the second and third trimesters and the placental transcriptome at birth, including genes and long noncoding RNAs (lncRNAs), to gain insight into potential mechanisms of action during fetal development.MethodsThe ECHO PATHWAYs consortium quantified 21 urinary phthalate metabolites from 760 women enrolled in the CANDLE study (Shelby County, TN) using high-performance liquid chromatography-tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate separate associations between maternal urinary phthalate metabolite concentration during the second and third trimester and placental gene expression at birth, adjusted for confounding variables. Genes were considered differentially expressed at a Benjamini-Hochberg false discovery rate (FDR) p

Neurodivergence encompasses a spectrum of natural variations in neurological development, including autism, ADHD, and other expressions of cognitive diversity. Caregiver experiences while supporting their neurodivergent dependents critically influence the quality of life outcomes for neurodivergent dependents across life stages, including during the search for work. However, research on caregiver experiences during this stage remains scarce, especially within lesser studied developing contexts like Thailand. This study explored perspectives of Thai caregivers preparing neurodivergent dependents for employment through a focus group (n = 10) of pre-vocational training caregivers and interviews (n = 13) with post-training caregivers. Analysis revealed significant sociocultural factors introducing stigma that affected acceptance, diagnosis, interventions, and policy support. Both groups reported systemic barriers, doubts about future independence, and hopes to increase advocacy and inclusive attitudes. However, caregivers whose dependents had received the training showed marked shifts in their expectations for their dependents' success. Tailored vocational preparation helping dependents exhibit strengths may transform societal views on neurodiversity from deficiency to natural diversity and enable more meaningful, sustainable futures. These insights elucidate caregiver challenges and aspirations, which can better inform supportive research and interventions in Thailand and other non-Western locales.

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4–6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother–child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.

Background: Consuming ultra-processed foods may increase exposure to phthalates, a group of endocrine disruptors prevalent in food contact materials. Objectives: Investigate associations between ultra-processed food intake and urinary phthalates during pregnancy, and evaluate whether ultra-processed foods mediate socioeconomic disparities in phthalate exposures. Methods: In a socioeconomically diverse sample of 1031 pregnant women from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study in the urban South, the Block Food Frequency Questionnaire was administered and urinary phthalate metabolites were measured in the second trimester. Linear regressions modeled associations between phthalates and overall ultra-processed food consumption, individual ultra-processed foods, and exploratory factor analysis dietary patterns. Causal mediation analyses examined whether ultra-processed food intake mediates relationships between socioeconomic disparities and phthalate exposures. Results: Ultra-processed foods constituted 9.8–59.0 % (mean = 38.6 %) of participants’ diets. 10 % higher dietary proportion of ultra-processed foods was associated with 13.1 % (95 %CI: 3.4 %–22.9 %) higher molar sum concentrations of di(2-ethylhexyl) phthalate metabolites (ΣDEHP). 10 % higher consumption of minimally-processed foods was associated with lower ΣDEHP (10.8 %: 3.4 %–22.9 %). Ultra- and minimally-processed food consumption were not associated with non-DEHP metabolites. Standard deviation higher consumptions of hamburger/cheeseburger, French fries, soda, and cake were associated with 10.5 % (4.2 %-17.1 %), 9.2 % (2.6 %-16.2 %), 7.4 % (1.4 %-13.6 %), and 6.0 % (0.0 %-12.4 %), respectively, higher ΣDEHP. Exploratory factor analysis corroborated positive associations of processed food with ΣDEHP, and uncovered a healthy dietary pattern associated with lower urinary ΣDEHP, mono(2-ethyl-5-hydroxyhexyl) (MEHHP), mono(2-ethyl-5-carboxypentyl) (MECPP), mono(2-carboxymethylhexyl) (MCMHP), and mono-isononyl (MINP) phthalates. Significant indirect effects indicated that lower income and education levels were associated with 1.9 % (0.2 %-4.2 %) and 1.4 % (0.1 %-3.3 %) higher ΣDEHP, respectively, mediated via increased ultra-processed food consumption. Conclusions: Consumption of ultra-processed foods may increase exposure to phthalates. Policies to reduce dietary phthalate exposures from food packaging and processing are needed, as socioeconomic barriers can preclude dietary recommendations as a sole means to reduce phthalate exposures.

Purpose: This case report highlights scleral perforation as a complication of diode laser transscleral cyclophotocoagulation in the treatment of refractory primary open-angle glaucoma, as well as the management of this complication. Observations: A 78-year-old woman with primary open-angle glaucoma refractory to medication had transscleral cyclophotocoagulation performed in her left eye. During the procedure, it was noted that conjunctival burns and scleral perforation had occurred, at which point the procedure was aborted. Limited peritomy and patch graft with split-thickness donor cornea was done in the area of the scleral thinning and perforation. The patient had a good outcome with an intraocular pressure of 8 mm Hg, appropriate integration of the patch graft, and no significant conjunctival inflammation at the 2-month post-operative visit. Conclusions and importance: This patient, without any known risk factors for scleral thinning or necrosis, experienced conjunctival burn as well as scleral perforation during transscleral cyclophotocoagulation, underscoring this possible complication of the procedure. Additionally, split-thickness donor cornea was used to patch graft the area of scleral thinning and perforation, which is a method of managing this complication that had not been previously reported.

BackgroundFindings from epidemiological studies of prenatal phthalate exposure and child cognitive development are inconsistent. Methods for evaluating mixtures of phthalates, such as weighted quantile sum (WQS) regression, have rarely been applied. We developed a new extension of the WQS method to improve specificity of full-sample analyses and applied it to estimate associations between prenatal phthalate mixtures and cognitive and language outcomes in a diverse pregnancy cohort.MethodsWe measured 22 phthalate metabolites in third trimester urine from mother-child dyads who completed early childhood visits in the Conditions Affecting Neurodevelopment and Learning in Early childhood (CANDLE) study. Language and cognitive ability were assessed using the Bayley Scales of Infant Development (age 3) and the Stanford Binet-5 (age 4-6), respectively. We used multivariable WQS regression to identify phthalate mixtures that were negatively and positively associated with language score and full-scale IQ, in separate models, adjusted for maternal IQ, race, marital status, smoking, BMI, socioeconomic status (SES), child age, sex, and breastfeeding. We evaluated effect modification by sex and SES. If full sample 95% WQS confidence intervals (which are known to be anti-conservative) excluded the null, we calculated a p-value using a permutation test (ppermutation). The performance of this new approach to WQS regression was evaluated in simulated data. We compared the power and type I error rate of WQS regression conducted within datasets split into training and validation samples (WQSSplit) and in the full sample (WQSNosplit) to WQS regression with a permutation test (WQSpermutation). Individual metabolite associations were explored in secondary analyses.ResultsThe analytic sample (N = 1015) was 62.1% Black/31.5% White, and the majority of mothers had a high school education or less (56.7%) at enrollment. Associations between phthalate mixtures and primary outcomes (language score and full-scale IQ) in the full sample were null. Individual metabolites were not associated with IQ, and only one metabolite (mono-benzyl phthalate, MBzP) was associated with Bayley language score (β = -0.68, 95% CI: -1.37, 0.00). In analyses stratified by sex or SES, mixtures were positively and negatively associated with outcomes, but the precision of full-sample WQS regression results were not supported by permutation tests, with one exception. In the lowest SES category, a phthalate mixture dominated by mono-methyl phthalate (MMP) and mono-carboxy-isooctyl phthalate (MCOP) was associated with higher language scores (βlow SES = 2.41, full-sample 95%CI: 0.58, 4.24; ppermutation = 0.04). Performance testing in simulated data showed that WQSpermutation had improved power over WQSSplit (90% versus 56%) and a lower type I error rate than WQSNosplit (7% versus 47%).ConclusionsIn the largest study of these relationships to date, we observed predominantly null associations between mixtures of prenatal phthalates and both language and IQ. Our novel extension of WQS regression improved sensitivity to detect true associations by obviating the need to split the data into training and test sets and should be considered for future analyses of exposure mixtures.

BackgroundPrenatal exposure to multiple phthalates is ubiquitous, and yet few studies have evaluated these exposures as a mixture in relation to child autistic traits and behavioral problems.ObjectivesTo assess cumulative associations between prenatal phthalate mixtures and child behaviors, including effect modification by exposure timing and child sex.MethodsAnalyses included 501 mother/child pairs from the multicenter pregnancy cohort The Infant Development and Environment Study (TIDES). Nine maternal urinary phthalate metabolites were measured in early and late pregnancy, and behavior was assessed at ages 4-5 years using composite T scores for the Behavioral Assessment System for Children (BASC-2), which measures several dimensions of child behavior, and the Social Responsiveness Scale (SRS-2), which measures social impairment consistent with autistic traits. We utilized weighted quantile sum (WQS) regressions to examine pregnancy period-specific associations between phthalate mixtures and behavioral outcomes. Full-sample 95% WQS confidence intervals are known to be anti-conservative, so we calculated a confirmatory p-value using a permutation test. Effect modification by sex was examined with stratified analyses.ResultsA one-quintile increase in the early pregnancy phthalate mixture was associated with increased SRS-2 total score (coefficient = 1.0, confirmatory p = 0.01) and worse adaptive skills (coefficient = -1.0, confirmatory p = 0.06) in both sexes. In sex-stratified analyses, the early pregnancy phthalate mixture was associated with increased SRS-2 total score in boys (coefficient = 1.2, confirmatory p = 0.04) and girls (coefficient = 1.0, confirmatory p = 0.10) and worse BASC-2 adaptive skills score in girls (coefficient = -1.5, confirmatory p = 0.06), while the late pregnancy phthalate mixture was associated with increased BASC-2 externalizing score in boys (coefficient = 1.3, confirmatory p = 0.03).ConclusionOur results suggest cumulative adverse associations between prenatal phthalate mixtures and multiple facets of childhood behavior.

Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.

Abstract Background Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in LMICs. Methods We searched Web of Science and PubMed for papers published between January 1, 2010, and December 31, 2021, that included components of both implementation science and economic evaluation. Studies from LMICs were prioritized for review, but papers from high-income countries were included if their methodology/findings were relevant to LMIC settings. Results Six thousand nine hundred eighty-six studies were screened, of which 55 were included in full-text review and 23 selected for inclusion and data extraction. Most papers were theoretical, though some focused on a single disease or disease subset, including: mental health (n = 5), HIV (n = 3), tuberculosis (n = 3), and diabetes (n = 2). Manuscripts included a mix of methodology papers, empirical studies, and other (e.g., narrative) reviews. Authorship of the included literature was skewed toward high-income settings, with 22 of the 23 papers featuring first and senior authors from high-income countries. Of nine empirical studies included, no consistent implementation cost outcomes were measured, and only four could be mapped to an existing costing or implementation framework. There was also substantial heterogeneity across studies in how implementation costs were defined, and the methods used to collect them. Conclusion A sparse but growing literature explores the intersection of implementation science and economic evaluation. Key needs include more research in LMICs, greater consensus on the definition of implementation costs, standardized methods to collect such costs, and identifying outcomes of greatest relevance. Addressing these gaps will result in stronger links between implementation science and economic evaluation and will create more robust and accurate estimates of intervention costs. Trial registration The protocol for this manuscript was published on the Open Science Framework. It is available at: https://osf.io/ms5fa/ (DOI: 10.17605/OSF.IO/32EPJ).

Emotionally arousing experiences are better remembered than neutral ones, highlighting that memory consolidation differentially promotes retention of experiences depending on their survival value. This paper reviews evidence indicating that the basolateral amygdala (BLA) mediates the facilitating influence of emotions on memory through multiple mechanisms. Emotionally arousing events, in part by triggering the release of stress hormones, cause a long-lasting enhancement in the firing rate and synchrony of BLA neurons. BLA oscillations, particularly gamma, play an important role in synchronizing the activity of BLA neurons. In addition, BLA synapses are endowed with a unique property, an elevated post-synaptic expression of NMDA receptors. As a result, the synchronized gamma-related recruitment of BLA neurons facilitates synaptic plasticity at other inputs converging on the same target neurons. Given that emotional experiences are spontaneously remembered during wake and sleep, and that REM sleep is favorable to the consolidation of emotional memories, we propose a synthesis for the various lines of evidence mentioned above: gamma-related synchronized firing of BLA cells potentiates synapses between cortical neurons that were recruited during an emotional experience, either by tagging these cells for subsequent reactivation or by enhancing the effects of reactivation itself.

Abstract Background People incarcerated in US prisons have been disproportionately harmed by the COVID-19 pandemic. That prisons are such efficient superspreading environments can be attributed to several known factors: small, communal facilities where people are confined for prolonged periods of time; poor ventilation; a lack of non-punitive areas for quarantine/medical isolation; and staggeringly high numbers of people experiencing incarceration, among others. While health organizations have issued guidance on preventing and mitigating COVID-19 infection in carceral settings, little is known about if, when, and how recommendations have been implemented. We examined factors contributing to containment of one of the first California prison COVID-19 outbreaks and remaining vulnerabilities using an adapted multi-level determinants framework to systematically assess infectious disease risk in carceral settings. Methods Case study employing administrative data; observation; and informal discussions with: people incarcerated at the prison, staff, and county public health officials. Results Outbreak mitigation efforts were characterized by pre-planning (e.g., designation of ventilated, single-occupancy quarantine) and a quickly mobilized inter-institutional response that facilitated systematic, voluntary rapid testing. However, several systemic- and institutional-level vulnerabilities were unaddressed hindering efforts and posing significant risk for future outbreaks, including insufficient decarceration, continued inter-facility transfers, incomplete staff cohorting, and incompatibility between built environment features (e.g., dense living conditions) and public health recommendations. Conclusions Our adapted framework facilitates systematically assessing prison-based infectious disease outbreaks and multi-level interventions. We find implementing some recommended public health strategies may have contributed to outbreak containment. However, even with a rapidly mobilized, inter-institutional response, failure to decarcerate created an overreliance on chance conditions. This left the facility vulnerable to future catastrophic outbreaks and may render standard public health strategies - including the introduction of effective vaccines - insufficient to prevent or contain those outbreaks.