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At least 91 records · Page 5

Plumbojarosite Remediation of Soil Affects Lead Speciation and Elemental Interactions in Soil and in Mice Tissues

Lead (Pb) contamination of soils is of global concern due to the devastating impacts of Pb exposure in children. Because early-life exposure to Pb has long-lasting health effects, reducing exposure in children is a critical public health goal that has intensified research on the conversion of soil Pb to low bioavailability phases. Recently, plumbojarosite (PLJ) conversion of highly available soil Pb was found to decrease Pb relative bioavailability (RBA <10%). However, there is sparse information concerning interactions between Pb and other elements when contaminated soil, pre- and post-remediation, is ingested and moves through the gastrointestinal tract (GIT). Addressing this may inform drivers of effective chemical remediation strategies. In this study, we utilize bulk and micro-focused Pb X-ray absorption spectroscopy to probe elemental interactions and Pb speciation in mouse diet, cecum, and feces samples following ingestion of contaminated soils pre- and post-PLJ treatment. RBA of treated soils was less than 1% with PLJ phases transiting the GIT with little absorption. In contrast, Pb associated with organics was predominantly found in the cecum. These results are consistent with transit of insoluble PLJ to feces following ingestion. The expanded understanding of Pb interactions during GIT transit complements our knowledge of elemental interactions with Pb that occur at higher levels of biological organization.

54 ENVIRONMENTAL SCIENCES↗

Timing based clustering of childhood BMI trajectories reveals differential maturational patterns; Study in the Northern Finland Birth Cohorts 1966 and 1986

Children’s biological age does not always correspond to their chronological age. In the case of BMI trajectories, this can appear as phase variation, which can be seen as shift, stretch, or shrinking between trajectories. With maturation thought of as a process moving towards the final state - adult BMI, we assessed whether children can be divided into latent groups reflecting similar maturational age of BMI. The groups were characterised by early factors and time-related features of the trajectories. We used data from two general population birth cohort studies, Northern Finland Birth Cohorts 1966 and 1986 (NFBC1966 and NFBC1986). Height (n = 6329) and weight (n = 6568) measurements were interpolated in 34 shared time points using B-splines, and BMI values were calculated between 3 months to 16 years. Pairwise phase distances of 2999 females and 3163 males were used as a similarity measure in k-medoids clustering. We identified three clusters of trajectories in females and males (Type 1: females, n = 1566, males, n = 1669; Type 2: females, n = 1028, males, n = 973; Type 3: females, n = 405, males, n = 521). Similar distinct timing patterns were identified in males and females. The clusters did not differ by sex, or early growth determinants studied. Trajectory cluster Type 1 reflected to the shape of what is typically illustrated as the childhood BMI trajectory in literature. However, the other two have not been identified previously. Type 2 pattern was more common in the NFBC1966 suggesting a generational shift in BMI maturational patterns.

60 APPLIED LIFE SCIENCES↗

ExpoKids: An R-based tool for characterizing aggregate chemical exposure during childhood

Background: Aggregate exposure, the combined exposures to a single chemical from all pathways, is a critical children’s health issue. Objective: The primary objective is to develop a tool to illustrate potential differences in aggregate exposure at various childhood lifestages and the adult lifestage. Methods: We developed ExpoKids (an R-based tool) using oral exposure estimates across lifestages generated by US EPA’s Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST). Results: ExpoKids is applied to illustrate aggregate oral exposure, for ten media, as average daily doses (ADD) and lifetime average daily doses (LADD) in five graphs organized across seven postnatal childhood lifestages and the adult lifestage. This data visualization tool conveys ExpoFIRST findings, from available exposure data, to highlight the relative contributions of media and lifestages to chemical exposure. To evaluate the effectiveness of ExpoKids, three chemical case examples (di[2-ethylhexyl] phthalate [DEHP], manganese, and endosulfan) were explored. Data available from the published literature and databases for each case example were used to explore research questions regarding media and lifestage contributions to aggregate exposure. Significance: These illustrative case examples demonstrate ExpoKids’ versatile application to explore a diverse set of children’s health risk assessment and management questions by visually depicting specific media and lifestage contributions to aggregate exposure.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Measured Indoor Nitrogen Oxides in Homes with a Child with Asthma and Gas or Induction Electric Cooking

The Cooking Energy and Ventilation Impacts on Children's Asthma (CEVICA) study is a randomized control trial investigating the effects of replacing gas with induction electric ranges in the homes of children with asthma in California's San Joaquin Valley. Indoor air quality parameters and respiratory health indicators were measured over 2-week intensive at Baseline and after consecutive 3-month study phases, with half getting electric cooking at the start of Phase 1 and others in Phase 2. Indoor air measurements included time-integrated NO 2 and NO X by passive sampler and time-resolved NO 2 by electrochemical sensors. In the first 40 homes, data were collected during 61 intensives for gas cooking and 55 for induction. Cooking was identified using temperature sensors above the cooktop. Pollutant events were identified from sharp rises in concentrations Time integrated NOX species were lower with electric cooking, with mean differences of 14.2 ppb for NO 2 (95% CI: 9.6, 18.7; p < 0.001), 55.6 ppb for NO X (95% CI: 30.4, 80.9; p < 0.001), and 41.5 ppb for derived NO (95% CI: 19.7, 63.2; p < 0.001). A paired, within home analysis showed larger reductions in Group 2 (gas to induction) than Group 1 that remained electric across Phase 1 and Phase 2 for NO 2 (mean difference in As of 10.5 ppb; 95% CI: 5.6, 15.4; p < 0.001), NO X (32.3 ppb; 95% CI: 10.0, 54.5; p=0.007), and derived NO (21.8 ppb; 95% CI: 3.6, 40.0; p=0.022). Compared to electric cooking, gas had much higher rates of associated NO 2 events, and larger above-baseline NO 2 peaks. These preliminary results are consistent with prior findings that shifting to induction cooking can substantially lower indoor NO 2 compared with gas cooking.

Fang, Yi↗

Range Hood Use and Effectiveness in Reducing Indoor Air Pollution During Gas and Induction Cooking

The Cooking Energy and Ventilation Impacts on Children's Asthma (CEVICA) study measured cooking frequency, range hood use, indoor air quality and respiratory health indicators of children with asthma living in homes with gas stoves in California's San Joaquin Valley. The study installed electric induction stoves and repeated measurements over three 2-week intensive periods, at baseline and at the end of two consecutive 3-month study phases. Stove replacements occurred at the start of Phase 1 or Phase 2 by random assignment. There were 4184 cooking events identified by automated analysis of time-series data from temperature sensors mounted above the cooktops and 1038 related range hood usage events detected from data recorded by anemometers, smart plugs, or motor loggers. Analysis of 1-minute resolved PM2.5 and NO 2 data identified and quantified 2685 PM 2.5 events and 2606 NO 2 events. Range hood use was characterized as a binary variable (>3 min vs. <3 min use). Range hood use was more common during cooking events associated with particle emissions and longer cooking durations. PM 2.5 concentrations during events with range hood use were comparable to those without use, which could result from limited effectiveness or if range hoods were preferentially used during higher-emission cooking scenarios. In homes with gas cooking, integrated NO 2 concentrations were about 45 percent higher during cooking events with no range hood use compared to those range hood use. The lowest pollutant levels were observed when the range hood operated for more than half of the cooking duration. These findings show that operation of venting range hood during cooking can substantially reduce short-term indoor exposure NO 2 in homes with gas cooking.

Fang, Yi↗

Measured indoor PM2.5, black carbon, and oxidative potential before and after replacing gas with induction cooking in asthmatic households

Cooking is a major source of fine particulate matter (PM) in homes and evidence to date is inconclusive about the impact of cooking fuel on measures of residential PM exposure. The Cooking Energy and Ventilation Impacts on Children's Asthma (CEVICA) study measured cooking frequency, range hood use, indoor air quality (IAQ) and respiratory health indicators of children with asthma living in homes with gas stoves in California's San Joaquin Valley. Intensive measurements occurred over three 2-week intensive periods: at baseline and at the end of two consecutive 3-month study phases. Participants were randomly assigned to have their gas stoves replaced with electric induction at the start of Phase 1 or Phase 2. As part of the IAQ assessment, we collected particulate matter on Teflon filters using ultrasonic personal air samplers (UPAS). The filters were analyzed to quantify time-integrated PM 2.5 mass concentration, black carbon (BC) oxidative potential (OP). OP was measured using the SLF-OH assay, an acellular chemical assay that quantifies production of OH radicals in simulated lung fluid (SLF). Across all comparisons, PM 2.5 mass tended to be higher during gas cooking than induction electric cooking, although only one transition (Baseline to Phase 1) was statistically discernible at p<0.05. BC and mass-normalized OP showed no measurable differences across stove types or across phases. These preliminary findings suggest that stove fuel alone may not be the dominant determinant of indoor PM 2.5 concentrations in this sample, as previous studies have reported that indoor PM 2.5 during cooking can also be influenced by factors such as cooking practices, food and oil type, kitchen ventilation, and outdoor infiltration.

Lin, Zhuoying↗

A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.

60 APPLIED LIFE SCIENCES↗

Structure-Based Design and Antigenic Validation of Respiratory Syncytial Virus G Immunogens

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of children, the elderly, and immunocompromised individuals. Currently, there are no FDA-approved RSV vaccines. The RSV G glycoprotein is used for viral attachment to host cells and impairment of host immunity by interacting with the human chemokine receptor CX3CR1. Antibodies that disrupt this interaction are protective against infection and disease. Nevertheless, development of an RSV G vaccine antigen has been hindered by its low immunogenicity and safety concerns. A previous study described three engineered RSV G proteins containing single-point mutations that induce higher levels of IgG antibodies and have improved safety profiles compared to wild-type RSV G. However, it is unclear if the mutations affect RSV G protein folding and display of its conformational epitopes. In this study, we show that the RSV G S177Q protein retains high-affinity binding to protective human and mouse monoclonal antibodies and has equal reactivity as wild-type RSV G protein to human reference immunoglobulin to RSV. Additionally, we determined the high-resolution crystal structure of RSV G S177Q protein in complex with the anti-RSV G antibody 3G12, further validating its antigenic structure. These studies show for the first time that an engineered RSV G protein with increased immunogenicity and safety retains conformational epitopes to high-affinity protective antibodies, supporting its further development as an RSV vaccine immunogen. Respiratory syncytial virus (RSV) causes severe lower respiratory diseases of children, the elderly, and immunocompromised populations. There currently are no FDA-approved RSV vaccines. Most vaccine development efforts have focused on the RSV F protein, and the field has generally overlooked the receptor-binding antigen RSV G due to its poor immunogenicity and safety concerns. However, single-point mutant RSV G proteins have been previously identified that have increased immunogenicity and safety. In this study, we investigate the antibody reactivities of three known RSV G mutant proteins. We show that one mutant RSV G protein retains high-affinity binding to protective monoclonal antibodies, is equally recognized by anti-RSV antibodies in human sera, and forms the same three-dimensional structure as the wild-type RSV G protein. Our study validates the structure-guided design of the RSV G protein as an RSV vaccine antigen.

59 BASIC BIOLOGICAL SCIENCES↗

Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data

Abstract Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children’s longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010–2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed ( N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days ( smoke-day ) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1–12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13–24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

Dhingra, Radhika↗

The progeria research foundation 10 th international scientific workshop; researching possibilities, ExTENding lives – webinar version scientific summary

Progeria is an ultra-rare (prevalence 1 in 20 million), fatal, pediatric autosomal dominant premature aging disease caused by a mutation in the LMNA gene. This mutation results in accumulation of a high level of an aberrant form of the nuclear membrane protein, Lamin A. This aberrant protein, termed progerin, accumulates in many tissues and is responsible for the diverse array of disease phenotypes. Children die predominantly from premature atherosclerotic cardiovascular disease. The Progeria Research Foundation’s 10th International Scientific Workshop took place via webinar on November 2 and 3, 2020. Participants from 30 countries joined in this new, virtual meeting format. Patient family presentations led the program, followed by updates on Progeria’s first-ever application for FDA drug approval as well as initial results from the only current Progeria clinical trial. This was followed by presentations of unpublished preclinical data on drugs in development targeting the disease-causing DNA mutation, the aberrant mRNA, progerin protein, and its downstream effector proteins. Tying bench to bedside, clinicians presented new discoveries on the natural history of disease to inform future clinical trial development and new Progeria aortic valve replacement procedures. The program engaged the Progeria research community as a single unit with a common goal – to treat and cure children with Progeria worldwide.

60 APPLIED LIFE SCIENCES↗

Timing based clustering in the Northern Finland Birth Cohorts 1966 and 1986 suggests two new patterns for childhood BMI curve [Poster]

Childhood body mass index (BMI) is a widely used measure of adiposity in children (<18 years of age). Children grow with individual tempo and individuals of the same age, or of the same BMI, might be in different phases in their individual growth curves. Variability between different childhood BMI curves can be separated in two components: phase variability (x-axis; time) and amplitude variability (y-axis; BMI). Phase variability can be thought of arising from differences in maturational age between individuals. This is related to the timing of peaks and valleys in a child’s BMI curve.

59 BASIC BIOLOGICAL SCIENCES↗

Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia

Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored. Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children ( n = 44, aged <48 mos) with either mild malarial anemia (M l MA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb <6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT 2 Profiler PCR Array containing a set of 84 human ubiquitination genes. Results: In children with SMA, 10 genes were down-regulated ( BRCC3 , FBXO3 , MARCH5 , RFWD2 , SMURF2 , UBA6 , UBE2A , UBE2D1 , UBE2L3 , UBR1 ), and five genes were up-regulated ( MDM2 , PARK2 , STUB1 , UBE2E3 , UBE2M ). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes. Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.

60 APPLIED LIFE SCIENCES↗

Toddler home math environment: Triangulating multi-method assessments in a U.S. Sample

Introduction Current research has documented the home math environment (HME) of preschoolers and kindergarteners. Very few studies, however, have explored the number and spatial activities in which parents engage with children during their toddler years. Methods This study examined the HME of 157 toddlers using several methodologies, including surveys, time diaries, and observations of math talk. Further, it examined correlations within and across data sources to identify areas of convergence and triangulation, and correlated HME measures with measures of toddlers’ number and spatial skills. Results Findings showed that, in general, uses of different types of math activities, including both number and spatial, were intercorrelated within method. Across methods, there was high intercorrelation between the frequency of math activities reported on parent surveys and the diversity of types of math activities endorsed in time diary interviews. Parent math talk gleaned from semi-structured interviews functioned as a separate aspect of the HME; different types of math talk shared few intercorrelations with engagement in math activities as reported in either surveys or time diaries. Finally, several HME measures positively correlated with toddlers’ math skills. Discussion Given extant research demonstrating that both math activities and math talk predict children’s math skills, our results stress the need for multimethod studies that differentiate among these HME opportunities.

Miller, Portia↗

The Eco-Bio-Social Factors That Modulate Aedes aegypti Abundance in South Texas Border Communities

Aedes aegypti control requires dedicated resources that are usually scarce, limiting the reach and sustainability of vector control programs. This generates a need to focus on areas at risk of disease transmission and also understand the factors that might modulate local mosquito abundance. We evaluated the eco-bio-social factors that modulate indoor and outdoor relative abundance of female Ae. aegypti in communities of South Texas. We conducted housing quality and Knowledge Attitudes and Practices surveys in households that were part of a weekly mosquito surveillance program in November of 2017 and 2018. Our results showed widespread knowledge of mosquitoes and Zika virus by our participants. However, less than 35% considered them as serious problems in this region. The presence of window-mounted air conditioning units increased the risk of female mosquito relative abundance indoors. An increase in outdoor relative abundance was associated with larger properties and a higher number of children between 6 to 17 years of age. Interestingly, we observed that an increasing number of children <5 years of age modulated both indoor and outdoor relative abundance, with a 52% increase indoors and 30% decrease outdoors. The low perception of mosquito and disease risk highlights engagement needs for vector-borne disease prevention in this region. The identified risk factors can help guide public health officials in their efforts to reduce human and vector contact.

54 ENVIRONMENTAL SCIENCES↗

Gender Gaps in Mode Usage, Vehicle Ownership, and Spatial Mobility When Entering Parenthood: A Life Course Perspective

Entry into parenthood is a major disruptive event to travel behavior, and gender gaps in mobility choices are often widened during parenthood. The exact timing of gender gap formation and their long-term effects on different subpopulations are less studied in the literature. Leveraging a longitudinal dataset from the 2018 WholeTraveler Study, this paper examines the effects of parenthood on a diverse set of short- to long-term outcomes related to the three hierarchical domains of mobility biography: mode choice, vehicle ownership, spatial mobility, and career decisions. The progress of the effects is evaluated over a sequential set of parenting stages and differentiated across three subpopulations. We find that individuals classified as “Have-it-alls”, who start their careers, partner up, and have children concurrently and early, significantly increase their car uses two years prior to childbirth (“nesting period”), and they then relocate to less transit-accessible areas and consequently reduce their reliance on public transportation while they have children in the household. In contrast, individuals categorized as “Couples”, who start careers and partnerships early but delay parenthood, and “Singles”, who postpone partnership and parenthood, have less pronounced changes in travel behavior throughout the parenting stages. The cohort-level effects are found to be driven primarily by women, whose career development is on average more negatively impacted by parenting events than men, regardless of their life course trajectory. Early career decisions made by women upon entering parenthood contribute to gender gaps in mid- to longer-term mobility decisions, signifying the importance of early intervention.

Yang, Hung-Chia (ORCID:0000000161439904)↗

Activity Time-Use Patterns and Experienced Satisfaction: Travel Behavioral Dynamics from the 2010–2013 American Time-Use Survey Data

Central to the theory of activity-based approaches is the role of time-use and its impacts on various decision processes related to individual activity-travel patterns, thereby determining ones’ daily well-being. This research aims at quantifying and investigating the underlying correlation of time-use and happiness using the repeated cross-section data from the 2010-2013 American Time Use Survey Well-Being module. The survey specifically records reported levels of activity satisfaction as measured through – happiness, meaningfulness, tiredness, sadness and stress experienced from activity participation. Using these scores, we first construct a composite degree of activity satisfaction that a person experiences using latent class cluster analysis. A series of regression models are then estimated to jointly analyze episodic duration and satisfaction separately for each of years from 2010-2013, by controlling for socioeconomics, household lifecycle stages (29-groups based on age, gender, marital status and presence of children), activity characteristics and global life and health assessment measures. Overall, model estimation results reveal a strong negative correlation between episodic duration and happiness from individual activity engagement patterns. This correlation pattern is temporally stable for the years 2010-2013, with minor variations. Results also suggest that household lifecycle stage has a major impact on activity time-use and satisfaction behavior. Further, single parent and younger couples (25 years to 45 years) with children are more likely to engage in longer and less happy episodes due to family commitments. The model findings also show a strong correlation between health conditions and activity happiness.

Ravulaparthy, Srinath↗

Salivary and Dental Complications in Childhood Cancer Survivors Treated With Radiation Therapy to the Head and Neck: A Pediatric Normal Tissue Effects in the Clinic (PENTEC) Comprehensive Review

Radiation therapy (RT) to the head and neck (H&N) region is critical in the management of various pediatric malignancies; however, it may result in late toxicity. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on salivary dysfunction and dental abnormalities in survivors who received RT to the H&N region as children.

62 RADIOLOGY AND NUCLEAR MEDICINE↗