The kidneys, heart and lungs are vital organ systems evaluated as part of acute or chronic toxicity assessments. New methodologies are being developed to predict these adverse effects based on in vitro and in silico approaches. This paper reviews the current state of the art in predicting these organ toxicities. It outlines the biological basis, processes and endpoints for kidney toxicity, pulmonary toxicity, respiratory irritation and sensitization as well as functional and structural cardiac toxicities. The review also covers current experimental approaches, including off-target panels from secondary pharmacology batteries. Current in silico approaches for prediction of these effects and mechanisms are described as well as obstacles to the use of in silico methods. Ultimately, a commonly accepted protocol for performing such assessment would be a valuable resource to expand the use of such approaches across different regulatory and industrial applications. However, a number of factors impede their widespread deployment including a lack of a comprehensive mechanistic understanding, limited in vitro testing approaches and limited in vivo databases suitable for modeling, a limited understanding of how to incorporate absorption, distribution, metabolism, and excretion (ADME) considerations into the overall process, a lack of in silico models designed to predict a safe dose and an accepted framework for organizing the key characteristics of these organ toxicants.

Background: Breastfeeding is recommended globally for most infants, especially during and after natural disasters when risk of adverse outcomes increases because of unsanitary conditions and lack of potable water. Materials and Methods: Using 2017-2019 data from Puerto Rico's Pregnancy Risk Assessment Monitoring System for 2,448 respondents with a recent live birth, we classified respondents into 4 hurricane exposure time periods based on infant birth month and year relative to when Hurricanes Irma and Maria occurred: (1) prehurricane; (2) acute hurricane; (3) posthurricane, early recovery; and (4) posthurricane, long-term recovery. We examined the association between maternity care practices during delivery hospitalization and exclusive breastfeeding at 3 months overall and stratified by time period. We also examined the associations between each maternity care practice and exclusive breastfeeding separately by time period. Results: Exclusive breastfeeding at 3 months was higher during the acute hurricane time period (adjusted prevalence ratio [aPR]: 1.43, 95% confidence interval: 1.09-1.87) than the prehurricane time period. Supportive maternity care practices were positively associated with exclusively breastfeeding, and practices that are risk factors for discontinuing breastfeeding were negatively associated with exclusive breastfeeding. Breastfeeding in the first hour (aPR range: 1.51-1.92) and rooming-in (aPR range: 1.50-2.58) were positively associated with exclusive breastfeeding across all time periods, except the prehurricane time period. Receipt of a gift pack with formula was negatively associated with exclusive breastfeeding (aPR range: 0.22-0.54) across all time periods. Conclusions: Maternity care practices during delivery hospitalization may influence breastfeeding behaviors and can improve breastfeeding during and after natural disasters. Strategies to maintain and improve these practices can be further supported during and after natural disasters.

BACKGROUND: Amalgam has been used for more than 150 years as a safe and reliable restorative material. The authors described the occurrence of amalgam and nonamalgam restorations in the United States in primary and permanent teeth across age groups and according to sociodemographic characteristics. METHODS: The authors used clinical examination data from the National Health and Nutrition Examination Survey 2015-2018 for participants 2 years and older (n = 17,040). The authors estimated the prevalence and mean number of amalgam and nonamalgam restorations in primary and permanent teeth according to age groups (2-5 years, 6-11 years, 12-15 years, 16-19 years, 20-39 years, 40-59 years, 60-79 years, and ≥ 80 years), race and ethnicity, federal poverty guideline, education, and pregnancy status. RESULTS: The prevalence of amalgam restorations ranged from 4% through 69%. Overall, amalgam restorations were more prevalent in children and adolescents from racial and ethnic minority groups and families at lower poverty levels and with lower education. The mean number of teeth with nonamalgam restorations was higher than those with amalgam restorations in primary teeth of children aged 6 through 11 years, permanent teeth of those 12 through 15 years and 20 through 39 years, and women aged 20 through 49 years, regardless of pregnancy status. The mean number of amalgam restorations was higher than that for nonamalgam restorations in older age groups. CONCLUSIONS: Nonamalgam restorations were the most common in the primary teeth of children older than 5 years and in the permanent teeth of adults younger than 40 years. Amalgam restorations were more common in older adults. Amalgam and nonamalgam restorations were equally common in children younger than 5 years. PRACTICAL IMPLICATIONS: The study findings suggest a shift from amalgam to alternative restorative materials in the United States.

OBJECTIVE: Exposure to natural disasters during and after pregnancy may increase adverse mental health outcomes. Hurricanes Irma and Maria struck Puerto Rico in September 2017. Our objectives were to understand hurricane-related experiences, maternal health concerns, and the impact of hurricane experiences on postpartum depressive symptoms (PDS). METHODS: We used data from the 2018 Pregnancy Risk Assessment Monitoring System to describe differences in maternal hurricane experiences among women who were pregnant during and after the 2017 hurricanes. We assessed maternal concerns and PDS. We estimated adjusted prevalence ratios (aPRs) and 95% CIs for the associations between hurricane experiences and PDS. RESULTS: The most frequently reported hurricane experiences were losing power for ≥1 week (97%) and feeling unsafe due to lack of order/security (70%). Almost 30% of women who were pregnant during the hurricanes reported missing prenatal care. PDS were reported by 13% of women. Most hurricane experiences were associated with an increased prevalence of PDS. Feeling unsafe (aPR = 2.4; 95% CI, 1.2-4.9) and having difficulty getting food (aPR = 2.1; 95% CI, 1.1-4.1) had the strongest associations. CONCLUSIONS: Most women who were pregnant during or after hurricanes Irma and Maria struck Puerto Rico reported negative hurricane experiences, and most experiences were associated with an increased prevalence of PDS. Understanding the experiences of pregnant women during and after disasters and identifying risks for adverse mental health outcomes after pregnancy are important to inform emergency preparedness and prenatal and postpartum care.

OBJECTIVE: To assess the receipt of health care services among live-born infants of women with and without evidence of Zika virus (ZIKV) infection while pregnant during the 2016-2017 ZIKV outbreak in Puerto Rico. METHODS: We used data from the Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response study telephone surveys to examine maternal reports of the receipt of health care services by infants born in Puerto Rico from August through December 2016 and November through December 2017. Evidence of ZIKV infection was ascertained from the infant's birth certificate or was self-reported in the survey. RESULTS: Fourteen percent of women in 2016 and 9% in 2017 had evidence of ZIKV infection during pregnancy. Most infants of women with evidence of ZIKV received the recommended health care services in 2016 and 2017, respectively, including a hearing test (91% vs. 92%), developmental assessment (90% vs. 92%), and an eye exam (74% vs. 70%); fewer received a head scan (45% vs. 36%) and evaluation for physical therapy (17% vs. 10%). From 2016 to 2017, the proportion of infants having a personal doctor increased for all infants; for infants of women without evidence of ZIKV infection, receiving hearing, developmental, and eye assessments increased. CONCLUSION: Most infants of women with evidence of ZIKV infection during pregnancy received the recommended hearing and developmental assessments during the ZIKV outbreak. Experiences with increasing service capacity during the ZIKV outbreak can be evaluated to inform the response to future emergencies that affect maternal and child health.

Guatemala has held dog rabies mass vaccination campaigns countrywide since 1984, yet the virus remains endemic. To eliminate dog-mediated human rabies, dog vaccination coverage must reach at least 70%. The Guatemala rabies program uses a 5:1 human:dog ratio (HDR) to estimate the vaccination coverage; however, this method may not accurately reflect the heterogeneity of dog ownership practices in Guatemalan communities. We conducted 16 field-based dog population estimates in urban, semi-urban and rural areas of Guatemala to determine HDR and evaluate the standard 5:1. Our study-derived HDR estimates varied from 1.7-11.4:1 (average 4.0:1), being higher in densely populated sites and lowest in rural communities. The community-to-community heterogeneity observed in dog populations could explain the persistence of rabies in certain communities. To date, this is the most extensive dog-population evaluation conducted in Guatemala, and can be used to inform future rabies vaccination campaigns needed to meet the global 2030 rabies elimination targets.

The Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response study, implemented in Puerto Rico during the Zika virus outbreak (2016-2017) and after Hurricanes Irma and María (2017-2018), collected pregnancy-related data using postpartum hospital-based surveys and telephone follow-up surveys. Response rates of 75% or more were observed across five study surveys. The study informed programs, increased the Puerto Rico Department of Health's capacity to conduct maternal‒infant health surveillance, and demonstrated the effectiveness of this methodology for collecting data during public health emergencies. (Am J Public Health. 2022;112(4):574-578. https://doi.org/10.2105/AJPH.2021.306687).

More than 19% of third-graders in Georgia had untreated dental caries (tooth decay) in 2016–2017 (1). The national average among children of similar age (6–9 y) was 15.5% in 2013–2016 (2). Untreated tooth decay can cause pain and infection and impair eating, speaking, and learning. Among children it can lead to missed school days and lower academic performance (3). The most recent US data indicated that 34 million school hours were missed in 2007 as a result of acute unplanned dental care needs (4). | | Dental sealants (5), topical fluoride (6), and restorative care are effective in preventing tooth decay. Most caries-prevention programs are implemented at the local level. The prevalence of untreated tooth decay, however, varies by geographic area — ranging from 8.2% to 32% among third-graders across 29 states during 2013–2016 (1). By county, modeled estimates among children aged 6 to 9 years nationwide ranged from 4.9% to 65.2% (7). Thus, having local data on the risk of untreated tooth decay and dental workforce capacity is critical to effectively target dental safety-net programs for children at highest risk of untreated tooth decay. | | We developed a data visualization tool that maps county-level need for caries prevention and treatment programs and the distribution of dental safety-net programs in Georgia. This tool can be used by public health decision makers to 1) assess how well dental safety-net programs are currently allocated and 2) plan and target future programs.

Decreased use of health care services (1), increased exposure to occupational hazards, and higher rates of substance use (2) might contribute to men's poorer health outcomes when compared with such outcomes for women (3). During the transition to fatherhood, paternal health and involvement during pregnancy might have an impact on maternal and infant outcomes (4-6). To assess men's health-related behaviors and participation in fatherhood-related activities surrounding pregnancy, the Puerto Rico Department of Health and CDC analyzed data from the paternal survey of the Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response (PRAMS-ZPER)* study. Fewer than one half (48.3%) of men attended a health care visit for themselves in the 12 months before their newborn's birth. However, most fathers attended one or more prenatal care visits (87.2%), were present at the birth (83.1%), and helped prepare for the newborn's arrival (e.g., by preparing the home [92.4%] or purchasing supplies [93.9%]). These findings suggest that opportunities are available for public health messaging directed toward fathers during the perinatal period to increase attention to their own health and health behaviors, and to emphasize the role they can play in supporting their families' overall health and well-being.

We examined pregnant women's use of personal protective measures to prevent mosquito bites during the 2016-2017 Zika outbreak in Puerto Rico. Healthcare provider counseling on recommended measures was associated with increased use of insect repellent among pregnant women but not with wearing protective clothing.

We examined condom use throughout pregnancy during the Zika outbreak in Puerto Rico during 2016. Overall, <25% of women reported consistent condom use during pregnancy. However, healthcare provider counseling was associated with a 3-fold increase in consistent use, reinforcing the value of provider counseling in Zika prevention efforts.

This study examined the effect of demographic factors on Social Communication Questionnaire (SCQ) scores in children aged 30-68 months. Diagnoses of ASD were made after a gold standard evaluation that included the Autism Diagnostic Observation Schedule (ADOS), and the Autism Diagnostic Interview Revised (ADI-R). The relationship of demographic variables to SCQ scores was compared in two source populations: (a) children recruited from clinical and educational sources serving children who have ASD or other developmental disorders (CE) and (b) children recruited from birth certificates to represent the general population (BC). The impact of the demographic variables-child sex, child age, maternal language, maternal ethnicity, maternal education, maternal race, and household income-on total SCQ score were studied to examine their impact on the SCQ's performance. Demographic factors predicting the SCQ total score were used to generate ROCs. Factors that had a significant influence on SCQ performance were identified by examining the area under the ROCs. Optimal SCQ cut-points were generated for significant factors using the Youden's Index. Overall male sex, lower household income, lower maternal education and Black race predicted higher SCQ scores. In this sample, the most common optimum value for the SCQ cut-point across the different sociodemographic groups was 11. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Screeners are used to help identify children who are more likely to have ASD than their peers. Ideally screeners should be accurate for different groups of children and families. This study examined how well the Social Communication Questionnaire (SCQ) predicts ASD. We found that male sex, lower household income, lower maternal education and Black race were associated with higher SCQ scores. In this study an SCQ cut-point of 11 worked best across the different sociodemographic groups in our sample.

Background: Noncommunicable disease (NCD) risk factors increase the risk of adverse reproductive health outcomes and are becoming increasingly common in Brazil. Methods: We analyzed VIGITEL 2011 telephone survey data for 13,745 Brazilian women aged 18-44 years in a probabilistic sample from 26 Brazilian state capitals and the Federal District. We examined associations between NCD risk factors (fruit and vegetable intake, leisure time physical activity, alcohol consumption, smoking status, BMI and hypertension status) and race, education, and insurance using chi-square tests and multivariable logistic regression models, estimating the average marginal effects to produce adjusted relative risk ratios (aRRs). Analyses were conducted using SAS 9.3 survey procedures and weighted to reflect population estimates. Results: Women with less than a college education were more likely to report physical inactivity (adjusted relative risk (aRR) and 95% confidence interval = 1.1 (1.1-1.2)), smoking (aRR = 1.7 (1.3-2.2)), and self-reported diagnoses of hypertension (aRR = 2.0 (1.6-2.5)) compared to women with a college education or greater. Similarly, women without health insurance were more likely to report physical inactivity (aRR = 1.1 (1.1-1.2)), smoking (aRR = 1.4 (1.1-1.8)), and self-reported diagnoses of hypertension aRR = 1.4 (1.1-1.7)) compared to women with health insurance. Less variation was found by race and NCD risk factors. Conclusion: Targeted public health strategies and policies are needed to increase healthcare access and decrease educational and racial disparities in NCD risk factors among women of reproductive age in Brazil. © 2016.Published by Elsevier Inc.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes. Increasing evidence links Zika virus infection during pregnancy to adverse pregnancy and birth outcomes, including pregnancy loss, intrauterine growth restriction, eye defects, congenital brain abnormalities, and other fetal abnormalities (1,2). The virus has also been determined to be sexually transmitted.* Because of the potential risks associated with Zika virus infection during pregnancy, CDC has recommended that health care providers discuss prevention of unintended pregnancy with women and couples who reside in areas of active Zika virus transmission and do not want to become pregnant.dagger However, limitations in access to contraception in some of these areas might affect the ability to prevent an unintended pregnancy. As of March 16, 2016, the highest number of Zika virus disease cases in the United States and U.S. territories were reported from Puerto Rico. section sign The number of cases will likely rise with increasing mosquito activity in affected areas, resulting in increased risk for transmission to pregnant women. High rates of unintended and adolescent pregnancies in Puerto Rico suggest that, in the context of this outbreak, access to contraception might need to be improved (3,4). CDC estimates that 138,000 women of reproductive age (aged 15-44 years) in Puerto Rico do not desire pregnancy and are not using one of the most effective or moderately effective contraceptive methods, paragraph sign,** and therefore might experience an unintended pregnancy. CDC and other federal and local partners are seeking to expand access to contraception for these persons. Such efforts have the potential to increase contraceptive access and use, reduce unintended pregnancies, and lead to fewer adverse pregnancy and birth outcomes associated with Zika virus infection during pregnancy. The assessment of challenges and resources related to contraceptive access in Puerto Rico might be a useful model for other areas with active transmission of Zika virus.

BACKGROUND: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. OBJECTIVE: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. METHODS: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. RESULTS: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. CONCLUSIONS: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.

The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.

The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome.

Cryptosporidiosis is a parasitic disease caused by Cryptosporidium spp. In immunocompetent individuals, it usually causes an acute and self-limited diarrhea; in infants, infection with Cryptosporidium spp. can cause malnutrition and growth retardation, and declined cognitive ability. In this study, we described for the first time the distribution of C. parvum and C. hominis subtypes in 12 children in Mexico by sequence characterization of the 60-kDa glycoprotein (GP60) gene of Cryptosporidium. Altogether, 7 subtypes belonging to 4 subtype families of C. hominis (Ia, Ib, Id and Ie) and 1 subtype family of C. parvum (IIa) were detected, including IaA14R3, IaA15R3, IbA10G2, IdA17, IeA11G3T3, IIaA15G2R1 and IIaA16G1R1. The frequency of the subtype families and subtypes in the samples analyzed in this study differed from what was observed in other countries.

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.

OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression. METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods. RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83-1.51) for prenatal exposure, 0.88 (0.62-1.26) for exposure from birth to 1 month, 0.60 (0.36-0.99) for exposure from birth to 7 months, and 0.60 (0.32-0.97) for exposure from birth to 20 months. CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemken, Ethiopia, a highland region where only few cases had been reported before. We analyzed records of VL patients treated from May 25, 2005 to December 13, 2007 by the only VL treatment center in the area, maintained by Medecins Sans Frontieres-Ethiopia, Operational Center Barcelona-Athens. The median age was 18 years; 77.6% were male. The overall case fatality rate was 4%, but adults 45 years or older were five times as likely to die as 5-29 year olds. Other factors associated with increased mortality included HIV infection, edema, severe malnutrition, pneumonia, tuberculosis, and vomiting. The VL epidemic expanded rapidly over a several-year period, culminating in an epidemic peak in the last third of 2005, spread over two districts, and transformed into a sustained endemic situation by 2007.