Exposure to phthalates is common and difficult to avoid. However, intake of long-chain n-3 polyunsaturated fatty acids (n3PUFAs) may ameliorate negative effects on ovarian reserve by exposure to phthalates as both are involved in key processes of ovarian function. Among 139 women attending a fertility center in the Environment and Reproductive Health (EARTH) Study (2004-2017), we evaluated whether associations between urinary phthalate biomarkers and antral follicle count (AFC) were modified by tertiles of serum α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We used Poisson regression (for individual phthalate biomarkers) and quantile Q-computation (for mixtures) models adjusted for age, body mass index, prior smoking, number of urine samples and urinary specific gravity. We found that serum EPA + DHA levels modified the negative association of urinary phthalate biomarkers mixture with mean AFC (P for interaction = 0.23); sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) had the strongest effect modification (P interaction = 0.01). Specifically, phthalate biomarkers mixture and ∑DEHP were inversely related with AFC only among women in the low (P trend = 0.03 and < 0.001, respectively) and middle (P trend = 0.07 and 0.002) tertiles of serum EPA + DHA, but not among women in the high tertile (P trend = 0.56 and 0.93). No effect modifications were found by serum ALA. These findings suggest certain serum n3PUFAs may attenuate effects of phthalate exposure on ovarian reserve marker. Such interaction points toward select n3PUFAs as key modifiers of phthalate toxicity on ovarian health with potential implications for other women's reproductive health endpoints.

Onchocerca lupi is an emerging zoonotic parasite in the southwestern United States that typically involves a single site in the head and neck region and is not known to recur after treatment. Human infection with O. lupi is reported in seven cases in the endemic southwestern United States and others from the Old World. Most U.S. cases involved the head and neck, with several presenting with neuroinvasive cervical disease, which can lead to spinal cord injury and meningitis. Recurrent infection has not been described in humans after surgical intervention and/or anthelmintic therapy; however, one case required revision surgery to excise residual worm fragments and inflammation. We present a case of either relapse or reinfection with O. lupi at a separate anatomic location nearly 3 years after completing treatment.

Baylisascaris procyonis (raccoon roundworm), a parasite commonly found in raccoons (Procyon lotor), can cause severe disease in humans when it invades visceral organs or the ocular and central nervous systems. Without prompt treatment, B. procyonis infection can lead to serious complications and death. During September 2024, the Los Angeles County Department of Public Health was notified of two unrelated pediatric patients with neurologic signs and symptoms consistent with baylisascariasis, including behavioral change, lethargy, and gait instability. The first case occurred in an adolescent aged 14 years who had received a previous diagnosis of autism spectrum disorder and had a history of pica (i.e., ingestion of nonfood items); the second case occurred in a previously healthy child aged 15 months. Both were treated with albendazole and corticosteroids. The first patient returned to baseline neurologic status, but delays in diagnosis and treatment of the second patient resulted in severe neurologic sequelae. Epidemiologic investigations identified raccoon feces that had fallen from a rooftop latrine (i.e., a communal raccoon defecation site) as the possible source of exposure for the adolescent. No source of exposure was identified for the younger child. B. procyonis infection should be suspected and prompt treatment considered in patients with neurologic symptoms and cerebrospinal fluid or peripheral blood eosinophilia (>1,000 eosinophils/mL of blood), especially young children or persons with developmental disabilities or pica. In addition, the public should be aware of exposure prevention strategies, including preventing raccoon activity around properties, avoiding exposure to raccoon feces, and safely removing raccoon latrines.

BACKGROUND: Evidence on the association between maternal phenol exposure and inflammation during pregnancy is limited and inconsistent. OBJECTIVE: To evaluate associations between urinary phenol biomarkers and serum inflammatory cytokines across pregnancy, and to examine whether associations vary by trimesters. METHODS: We included 175 pregnant women from the Massachusetts General Hospital Fertility Center and participating in the Environment and Reproductive Health (EARTH) Study (2005-2017), with available data on urinary concentrations of eight phenol biomarkers and serum inflammatory biomarkers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Linear regression models were employed to assess the association between individual phenol biomarker concentrations and log-transformed inflammatory cytokine levels, while Bayesian Kernel Machine Regression (BKMR) models were utilized to evaluate phenol biomarker mixtures. Analyses were further stratified by the trimester of sample collection. RESULTS: Overall, detectable urinary ethylparaben was positively associated with serum hsCRP (β: 0.464; 95 % CI: 0.012, 0.917). In trimester-specific analyses, urinary butylparaben was positively associated with hsCRP (β: 0.533; 95 % CI: 0.006, 1.059) in the first trimester, but negatively associated with IL-6 (β: -0.613; 95 % CI: -1.062, -0.164) in the second trimester. Urinary bisphenol A was inversely associated with hsCRP (β: -0.428; 95 % CI: -0.731, -0.125) in the third trimester. CONCLUSIONS: Our findings suggest that exposure to certain phenols may disrupt inflammatory profiles in pregnancy, with effects varying by trimesters. These novel associations underscore the importance of exposure timing when assessing environmental risk factors for maternal and offspring health outcomes.

BACKGROUND: Few studies have evaluated the associations between phthalate exposures and maternal inflammation. OBJECTIVES: To examine cross-sectional associations of urinary phthalate metabolites, individually and as a mixture, with serum inflammatory biomarkers during pregnancy. METHODS: A total of 175 pregnant women enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 were included. Concentrations of 11 urinary phthalate metabolites and two serum inflammatory biomarkers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured. Urinary concentrations of phthalate metabolites were adjusted for specific gravity (SG) before analysis. Linear regression and Bayesian Kernel Machine Regression models were used to examine the associations for individual phthalates and their mixture, respectively. Stratified analyses by pre-pregnancy body mass index (BMI) were also conducted. RESULTS: No association for urinary phthalate metabolites, individually or as a mixture, was observed with serum CRP overall among pregnant women. Urinary mono-3-carboxypropyl phthalate and monocarboxyisooctyl phthalate were positively associated with serum IL-6 (β [95 % CI] per 1-SD increase in log-transformed, SG-adjusted concentrations: 0.09 [0.01, 0.16] and 0.09 [0.02, 0.17], respectively). Besides, urinary mono-isobutyl phthalate was positively associated with serum IL-6 among women with a pre-pregnancy BMI ≥25 kg/m(2) (β [95 % CI] per 1-SD increase: 0.15 [0.00, 0.30]), but not with lower BMI (-0.03 [-0.12, 0.07]). A suggestive positive association between phthalate mixture and serum IL-6 was observed in the high pre-pregnancy BMI group. CONCLUSIONS: Our findings suggest that women with a higher pre-pregnancy BMI may be more vulnerable to the effects of certain phthalates on maternal inflammation reflected by IL-6.

BACKGROUND: Phthalate exposures are ubiquitous and have been associated with pregnancy complications. Interaction between serum long-chain n-3 polyunsaturated fatty acids (n3PUFA) and phthalate biomarkers is biologically plausible because both can bind to human peroxisome proliferator-activated receptors (PPARs) which are involved in placenta development. However, evidence of this interaction in humans is lacking. OBJECTIVE: To evaluate whether serum n3PUFA modifies the associations of biomarkers of phthalate exposure on pregnancy outcomes. METHODS: Among 351 women undergoing in vitro fertilization in the Environment and Reproductive Health study (2004-2017), we evaluated the effect modification of eicosapentaenoic acid (EPA) and serum docosahexaenoic acid (DHA) on the association of pregnancy outcomes with the mixture of urinary concentrations of phthalate biomarkers by quantile g-computation. All models were adjusted for age, body mass index, prior smoking, infertility diagnosis, treatment year, and urinary specific gravity. RESULTS: Concentrations of the phthalate biomarkers mixture were associated with higher adjusted probabilities of pregnancy loss and lower estimated probabilities of live birth among women with serum EPA+DHA in the lowest tertile (< 2.66% of total fatty acids), but not among women with middle-to-high serum EPA+DHA (p interactions = 0.06 and 0.15, respectively). Among women in the lowest tertile of serum EPA+DHA, the adjusted probability [95% confidence interval (CI)] of pregnancy loss for women in the lowest and highest quartile of phthalates mixtures was 5% (2%, 16%) and 44% (23%, 85%), respectively (p trend = 0.01). The corresponding estimates were 14% (5%, 41%) and 11% (3%, 42%) among women with serum EPA+DHA in the highest tertile (⩾ 3.78% of total fatty acids) (p trend = 0.81). Similar trends were observed for live birth but not for implantation and clinical pregnancy. CONCLUSIONS: This study suggests adverse effects of phthalate exposure on pregnancy loss and live birth may be attenuated by intakes of n3PUFA. These results, if replicated, could inform clinical practice reducing the burden of infertility by phthalate exposure among the general population and improving pregnancy outcomes among subfertile couples.. https://doi.org/10.1289/EHP15942.

Workers in electronics waste and lamp recycling facilities are at risk of exposure to elemental mercury through inhalation of mercury vapor and mercury-containing dust. Employers at an electronics waste and lamp recycling facility in Ohio that crushes mercury-containing lamps expressed concerns about mercury exposure from work processes and requested a health hazard evaluation by CDC's National Institute for Occupational Safety and Health (NIOSH). In April 2023, NIOSH conducted a multidisciplinary investigation to assess elemental and inorganic mercury exposures, including epidemiologic, environmental, and ventilation assessments. Results indicated that mercury vapor was detected throughout the facility, with six of 14 workers having elevated urine mercury levels. These workers had a median job tenure of 8 months; four did not speak English, and five reported symptoms consistent with mercury toxicity, such as metallic or bitter taste, difficulty thinking, and changes in personality. Recommendations included improving the ventilation system, changing work practices to reduce mercury exposure, and providing training and communication tailored to the worker. As the electronic waste recycling industry continues to grow, it is important for employers to evaluate mercury exposure and safeguard employees using a hierarchy of controls. Health departments should consider monitoring occupational mercury exposure in recycling facilities, and clinicians should be aware of the potential for mercury toxicity among workers in these settings.

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

OBJECTIVE: Pet ownership among people experiencing homelessness (PEH) is common, but access to shelter, veterinary care, and flea-preventative products for PEH who own pets in the US is not well described. We sought to evaluate current knowledge of fleas and flea-borne diseases and characterize practices around pets and service animals among staff at homeless shelters and outreach organizations. METHODS: In-person surveys were administered to staff at homeless shelters and on outreach teams in 7 states from August 2022 to April 2023 to evaluate knowledge, attitudes, and practices and to assess homeless shelter/organizational characteristics. RESULTS: Surveys were administered to 333 staff members at 60 homeless shelters and among 29 outreach teams. Seventy-eight percent of homeless shelters allowed pets or service animals. Only 2% of homeless shelters and 7% of outreach teams provided veterinary care; 15% of homeless shelters and 7% of outreach teams provided flea preventatives. Nearly three-quarters of surveyed homeless shelter staff responded that no steps were taken to treat fleas at their shelters. CONCLUSIONS: Veterinary care and availability of flea-preventative products are limited in homeless shelter and outreach organizations serving people experiencing homelessness. CLINICAL RELEVANCE: Pets of PEH might be at an increased risk of flea infestation and flea-borne diseases because of limited access to veterinary care and preventatives. Improving knowledge and access to flea prevention, screening, and treatment are critical to ensure PEH and their pets can consistently access homeless shelters or outreach services, and to prevent flea-borne disease transmission.

BACKGROUND: Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. METHODS: In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004 and 2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n = 179), paternal preconception (n = 121), and maternal pregnancy (n = 177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. RESULTS: The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (β(maternal_precon) = -1.6, 95% CI -2.7; -0.4; β(paternal_precon) = -2.9, 95% CI -4.6; -1.2) for each log(e) increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. CONCLUSIONS: Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

Phthalates are ubiquitous pollutants in the environment; however, the mechanisms of phthalate-associated reproductive disorders in men are not fully understood. The aim of this study is to investigate associations between urinary phthalate metabolite concentrations and sperm DNA methylation. The study was conducted on 697 men from three prospective pregnancy cohorts: Longitudinal Investigation of Fertility and the Environment (LIFE) Study, Sperm Environmental Epigenetics and Development Study (SEEDS), and Environment and Reproductive Health (EARTH) Study. Eighteen phthalate and two phthalate alternative metabolites were quantified by mass spectrometry in preconception urinary samples and sperm DNA methylation was measured via Illumina EPIC Array (v1). Regional methylation analyses were conducted to identify cohort-specific loci associated with urinary phthalate metabolites. Models were adjusted for age, body mass index (BMI), race, smoking status, urinary creatinine/specific gravity, and analytical batch for phthalate measurements. The cohort-specific results were meta-analyzed using METAL. Participants had an average age of 30 years, most (79.6 %) of whom had BMI>25 kg/m(2) and were non-smokers (90.1 %). A total of 7,979 differentially methylated regions (DMRs; 7,979 LIFE-specific DMRs, 72 SEEDS-specific DMRs, and 23 EARTH-specific DMRs) were associated with urinary MBzP, MiBP, MMP, MCNP, MCPP, MBP, and MCOCH. Meta-analysis identified fewer DMRs than cohort-specific models: 946 DMRs were associated with MBzP, 27 DMRs associated with MiBP, and 1 DMR associated with MEHP. The majority of cohort-specific and meta-analysis-derived DMRs displayed a positive association with phthalate metabolite concentrations and were enriched in genes associated with spermatogenesis, response to hormones and their metabolism, embryonic organ development and developmental growth. In conclusion, several preconception urinary phthalate metabolites were associated with increased DNA methylation patterns in sperm. These findings provide an epigenetic pathway by which environmental phthalate exposures can impact couples' reproductive outcomes.

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings.

OBJECTIVE: To evaluate the association between urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health (EARTH) Study seeking fertility treatment at Massachusetts General Hospital in Boston, Massachusetts. DESIGN: Prospective cohort study. METHODS: Women from the EARTH cohort contributed spot urine samples before assessment of OR outcomes. Antral follicle count (AFC) and day-3 follicle stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of specific gravity (SG)-adjusted urinary benzophenone-3 concentrations with AFC and FSH, respectively, with adjustment for age and physical activity. In secondary analyses, models were stratified by age. Sensitivity analyses assessed for confounding by season by restricting to women with exposure and outcome measured in the same season and stratifying by summer vs. non-summer months and for confounding by sunscreen use by restricting to women who filled out product questionnaires and adjusting for and stratifying by average sunscreen use score. RESULTS: The study included 142 women (mean age ± SD, 36.1 ± 4.6; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC and 57 women with benzophenone-3 and FSH measurements. Most women were white (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10) with 37% contributing 2 or more samples. Benzophenone-3 was detected in 98% of samples. Geometric mean (GM) SG-corrected urinary benzophenone-3 concentration was 85.9 μ g/L (geometric standard deviation 6.2). There were no associations of benzophenone-3 with AFC and day-3 FSH in the full cohort. In stratified models, a 1-unit increase in log GM benzophenone-3 was associated with AFC 0.91 (95% CI, 0.86, 0.97) times lower among women ≤35 years old and was associated with FSH 0.73 (95% CI, 0.12, 1.34) IU/L higher among women >35 years old. Effect estimates from models stratified by season and sunscreen use were null. CONCLUSION: In main models, urinary benzophenone-3 was not associated with OR. However, younger may be vulnerable to potential effects of benzophenone-3 on AFC. Further research is warranted.

BACKGROUND AND AIMS: Louse-borne Bartonella quintana infection and flea-borne murine typhus are two potentially serious vector-borne diseases that have led to periodic outbreaks among people experiencing homelessness in the United States. Little is known about louse- and flea-borne disease awareness and prevention among staff who provide services to the population. We surveyed staff in seven US states to identify gaps in knowledge and prevention practices for these diseases. METHODS AND RESULTS: Surveys were administered to 333 staff at 89 homeless shelters and outreach teams in California, Colorado, Georgia, Maryland, Minnesota, New York and Washington from August 2022 to April 2023. Most participants (>68%) agreed that body lice and fleas are a problem for people experiencing homelessness. About half were aware that diseases could be transmitted by these vectors; however, most could not accurately identify which diseases. Less than a quarter of staff could describe an appropriate protocol for managing body lice or fleas. Misconceptions included that clients must isolate or be denied services until they are medically cleared. CONCLUSIONS: Our findings reveal significant knowledge gaps among staff who provide services to people experiencing homelessness in the prevention and control of louse- and flea-borne diseases. This demonstrates an urgent need for staff training to both reduce disease and prevent unnecessary restrictions on services and housing.

BACKGROUND: Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors. METHODS: We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores. RESULTS: This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (β(')s= 0.11 [95% CI: 0.01, 0.20]-0.21 [95% CI: 0.10, 0.31] per log(e) unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores. CONCLUSIONS: In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children.

BACKGROUND: Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6-13 years and their parents. We estimated covariate-adjusted associations of log(e) -transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g-computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 and Behavior Rating Inventory of Executive Function T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non-Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T-scores (propyl paraben β = 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β = 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben β = 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β = 1.6; 95% confidence interval: -0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T-scores respectively. Higher paternal preconception ( β = 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( β = 1.1 95% confidence interval: -0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T-scores in children, but the paraben mixtures was not. CONCLUSION: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors.

BACKGROUND: Epidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-log(e) unit increase; 95 % CI: -0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: -1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: -2.1, -0.4). CONCLUSION: In this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores.

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.

When new pathogens emerge, numerous questions arise about their future spread, some of which can be addressed with probabilistic forecasts. The many uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among model structures and assumptions, however. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance of a suite of 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about the role of human mobility in driving transmission, spatiotemporal variation in transmission potential, and the number of times the virus was introduced. All models used the same core transmission model and the same iterative data assimilation algorithm to generate forecasts. By assessing forecast performance through time using logarithmic scoring with ensemble weighting, we found that which model assumptions had the most ensemble weight changed through time. In particular, spatially coupled models had higher ensemble weights in the early and late phases of the epidemic, whereas non-spatial models had higher ensemble weights at the peak of the epidemic. We compared forecast performance of the equally-weighted ensemble model to each individual model and identified a trade-off whereby certain individual models outperformed the ensemble model early in the epidemic but the ensemble model outperformed all individual models on average. On balance, our results suggest that suites of models that span uncertainty across alternative assumptions are necessary to obtain robust forecasts in the context of emerging infectious diseases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementRJO acknowledges support from an Eck Institute for Global Health Fellowship, GLOBES grant, Arthur J. Schmitt Fellowship, and the UNICEF Office of Innovation. MUGK is supported by The Branco Weiss Fellowship - Society in Science, administered by the ETH Zurich and acknowledges funding from the Oxford Martin School and the European Union Horizon 2020 project MOOD (\#874850). SCH is supported by the Wellcome Trust (220414/Z/20/Z).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:No IRB approvals were necessary.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe mobile phone data set used in this study is proprietary and subject to strict privacy regulations. The access to this data set was granted after reaching a non-disclosure agreement with the proprietor, who anonymized and aggregated the original data before giving access to the authors. The mobile phone is available on request after negotiation of a non-disclosure agreement with the company. The contact person is Enrique Frias-Martinez (efm{at}tid.es). Epidemiological, meteorological, and demographic data are available from Siraj et al.2018 and additionally available on https://github.com/roidtman/eid_ensemble_forecasting. https://www.github.com/roidtman/eid_ensemble_forecasting

Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004-2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = -0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts.

Endocrine disrupting chemicals (EDCs) can adversely affect human health and are ubiquitously found in everyday products. We examined temporal trends in urinary concentrations of EDCs and their replacements. Urinary concentrations of 11 environmental phenols, 15 phthalate metabolites, phthalate replacements such as two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) metabolites, and triclocarban were quantified using isotope-dilution tandem mass spectrometry. This prospective ecological study included 996 male and 819 female patients who were predominantly White/Caucasian (83 %) with an average age of 35 years and a BMI of 25.5 kg/m(2) seeking fertility treatment in Boston, MA, USA. Patients provided a total of 6483 urine samples (median = 2, range = 1-30 samples per patient) between 2000 and 2017. Over the study period, we observed significant decreases (% per year) in urinary concentrations of traditional phenols, parabens, and phthalates such as bisphenol A (β: -6.3, 95 % CI: -7.2, -5.4), benzophenone-3 (β: -6.5, 95 % CI: -1.1, -18.9), parabens ((β range:-5.4 to -14.2), triclosan (β: -18.8, 95 % CI: -24, -13.6), dichlorophenols (2.4-dichlorophenol β: -6.6, 95 % CI: -8.8, -4.3); 2,5-dichlorophenol β: -13.6, 95 % CI: -17, -10.3), di(2-ethylhexyl) phthalate metabolites (β range: -11.9 to -22.0), and other phthalate metabolites including mono-ethyl, mono-n-butyl, and mono-methyl phthalate (β range: -0.3 to -11.5). In contrast, we found significant increases in urinary concentrations of environmental phenol replacements including bisphenol S (β: 3.9, 95 % CI: 2.7, 7.6) and bisphenol F (β: 6, 95 % CI: 1.8, 10.3), DINCH metabolites (cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester [MHiNCH] β: 20, 95 % CI: 17.8, 22.2; monocarboxyisooctyl phthalate [MCOCH] β: 16.2, 95 % CI: 14, 18.4), and newer phthalate replacements such as mono-3-carboxypropyl phthalate, monobenzyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate and di-isobutyl phthalate metabolites (β range = 5.3 to 45.1), over time. Urinary MHBP concentrations remained stable over the study period. While the majority of biomarkers measured declined over time, concentrations of several increased, particularly replacement chemicals that are studied.

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009-2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography-tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols-both individually and as a mixture-and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT(3) (mean difference for a 1 log unit increase in concentration: -0.088; 95% CI [-0.151, -0.025]) and TT(3) (-0.066; 95% CI [-0.112, -0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT(3) concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: -0.19, 95% CI [-0.35, -0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.

Tecovirimat (also known as TPOXX or ST-246) is a drug available for the treatment of mpox through the Centers for Disease Control and Prevention’s Expanded Access Investigational New Drug “compassionate use” protocol (https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.html). In Los Angeles County, a fatal case of mpox with tecovirimat resistance was previously reported (1). Epidemiologic surveillance in Los Angeles County has since identified additional cases of severe mpox that did not improve after multiple rounds of tecovirimat treatment, including one involving a person who succumbed to infection (Table 1). Consistent with reports describing severe manifestations of mpox within the current global outbreak (1, 2), the identified cases involved host immunodeficiency due to advanced HIV infection.

On August 1, 2018, the Democratic Republic of the Congo Ministry of Health (DRC MoH) declared the tenth outbreak of Ebola virus disease (Ebola) in DRC, in the North Kivu province in eastern DRC on the border with Uganda, 8 days after another Ebola outbreak was declared over in northwest Équateur province. During mid- to late-July 2018, a cluster of 26 cases of acute hemorrhagic fever, including 20 deaths, was reported in North Kivu province.* Blood specimens from six patients hospitalized in the Mabalako health zone and sent to the Institut National de Recherche Biomédicale (National Biomedical Research Institute) in Kinshasa tested positive for Ebola virus. Genetic sequencing confirmed that the outbreaks in North Kivu and Équateur provinces were unrelated. From North Kivu province, the outbreak spread north to Ituri province, and south to South Kivu province (1). On July 17, 2019, the World Health Organization designated the North Kivu and Ituri outbreak a public health emergency of international concern, based on the geographic spread of the disease to Goma, the capital of North Kivu province, and to Uganda and the challenges to implementing prevention and control measures specific to this region (2). This report describes the outbreak in the North Kivu and Ituri provinces. As of November 17, 2019, a total of 3,296 Ebola cases and 2,196 (67%) deaths were reported, making this the second largest documented outbreak after the 2014-2016 epidemic in West Africa, which resulted in 28,600 cases and 11,325 deaths.(†) Since August 2018, DRC MoH has been collaborating with partners, including the World Health Organization, the United Nations Children's Fund, the United Nations Office for the Coordination of Humanitarian Affairs, the International Organization of Migration, The Alliance for International Medical Action (ALIMA), Médecins Sans Frontières, DRC Red Cross National Society, and CDC, to control the outbreak. Enhanced communication and effective community engagement, timing of interventions during periods of relative stability, and intensive training of local residents to manage response activities with periodic supervision by national and international personnel are needed to end the outbreak.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,(†) predominantly among cisgender men(§) who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox(¶) (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

Since May 2022, when the multinational mpox (formerly known as monkeypox) clade IIb virus outbreak was first reported, more than 30,000 cases have been identified in the United States.1 In one study involving more than 1900 patients with mpox, more than 35% of the patients also had human immunodeficiency virus (HIV) infection.2 | | We report a death due to mpox in a patient in the United States. A 33-year-old man with HIV infection (CD4+ T-cell count, <35 per cubic millimeter) and recently treated syphilis became infected with mpox virus (MPXV) (clade IIb). He received two courses of oral tecovirimat (from Aug. 6 through Aug. 20, 2022, and from Aug. 21 through Sept. 4, 2022) and died on hospital day 27.

Risk for transmission of monkeypox virus (MPXV) (clade IIb) to healthcare workers (HCWs) is low. Although many cases have been reported among HCW, only a few have been occupationally acquired. We report a case of non-needle stick MPXV transmission to an HCW in the United States.

OBJECTIVE: Epidemiologic data for mixed connective tissue disease (MCTD) are limited. Leveraging data from the Manhattan Lupus Surveillance Program (MLSP), a racially/ethnically diverse population-based registry of cases with SLE and related diseases including MCTD, we provide estimates of the prevalence and incidence of MCTD. METHODS: MLSP cases were identified from rheumatologists, hospitals, and population databases using a variety of ICD-9 codes. MCTD was defined as one of the following: 1) fulfillment of our modified Alarcon-Segovia and Kahn criteria which required a positive RNP antibody and the presence of synovitis, myositis, and Raynaud's phenomenon, 2) a diagnosis of MCTD and no other diagnosis of another connective tissue disease (CTD), and 3) a diagnosis of MCTD regardless of another CTD diagnosis. RESULTS: Overall, 258 (7.7%) of cases met a definition of MCTD. Using our modified Alarcon-Segovia and Kahn criteria for MCTD, the age-adjusted prevalence was 1.28 (95%CI 0.72-2.09) per 100 000. Using our definition of a diagnosis of MCTD and no other diagnosis of another CTD yielded an age-adjusted prevalence and incidence of MCTD of 2.98 (95%CI 2.10-4.11) per 100 000 and 0.39 (95%CI 0.22-0.64) per 100 000, respectively. The age-adjusted prevalence and incidence were highest using a diagnosis of MCTD regardless of other CTD diagnoses and were 16.22 (95%CI 14.00-18.43) per 100 000 and 1.90 (95%CI 1.49-2.39) per 100 000 respectively. CONCLUSIONS: The MLSP provided estimates for prevalence and incidence of MCTD in a diverse population. The variation in estimates using different case definitions is reflective of the challenge of defining MCTD in epidemiologic studies.

In August 2022, the Los Angeles County Department of Public Health initiated an investigation into human monkeypox virus (MPXV) cases with unusual results from a multiplex laboratory-developed test used by Quest Diagnostics, which is based on the CDC nonvariola Orthopoxvirus (NVO) (1) and MPXV clade II (MPXV-WA) (2) real-time PCR assays. These specimens returned NVO–positive and either MPXV-WA–negative or positive results with high Ct values, which differ from the strong dual-positive results typically associated with the current outbreak. Since these patients met the case definition for probable human MPXV infection, (3) these discordant results were presumed to be due to a mutation affecting the performance of the MPXV-WA assay.