ABSTRACT
Ethnic minorities, such as Pasifika, residing in high-income countries were at higher risk of COVID-19 infection during the pandemic. To understand the experiences of Pasifika, including message dissemination and barriers to tailored public health messaging during the pandemic, a qualitative study was undertaken, underpinned by Laswell's Model of Communication and Bandura's social cognitive theory with data collected using Pasifika methods. Pasifika adults (n = 65) were recruited across Sydney from July 2020 to March 2022. Health care professionals (HCP) (n = 17) employed by four local health districts (LHDs) and Pasifika community-based organizations delivering multicultural COVID-19-related work within the study catchment, were also recruited. Five themes were constructed from the data of: (i) prevailing fear and uncertainty over COVID-19 infection and losing employment; (ii) limited knowledge of government perpetuating distrust in Government as a benevolent source of information; (iii) faith and trust as priorities for health decision-making; (iv) 'Coconut wireless'-the role of family, friends and community in disseminating public health messages through word of mouth; and (v) limited health literacy affecting compliance with public health orders. Community members identified important messages and resources had not been sufficiently distributed. Most HCPs understood the necessity of grassroots-level engagement but reported existing approaches were inadequate to navigate challenges. These findings highlight the need for public health promotion and communication strategies that consider both the social and cultural determinants of health. We propose a 7-point checklist as a cultural appropriateness lens to assist the development and rating of existing or new health promotion messaging and resources.
Subject(s)
COVID-19 , Ethnic and Racial Minorities , Adult , Humans , COVID-19/prevention & control , Australia , Communication , FearABSTRACT
OBJECTIVE: This study aimed to describe maternal characteristics and clinical outcomes of infants born to mothers with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests during pregnancy at an urban, safety-net hospital in Boston. STUDY DESIGN: We abstracted electronic chart data from 75 pregnant women with positive SARS-CoV-2 tests at any stage of gestation until 72 hours after birth who delivered consecutively between March 31 and August 6, 2020 at our center. We collected clinical data on maternal and infant characteristics, including testing, signs, and symptoms of coronavirus disease 2019 (COVID-19), delivery outcomes, newborn care practices (skin-to-skin care, location of care, and breastfeeding) and 30-day postdischarge infant emergency room visits and readmissions. We described categorical characteristics as percentages for this case series. RESULTS: Among 75 pregnant women, 47 (63%) were Hispanic, 10 (13%) had hypertension, 23 (30%) had prepregnancy obesity, and 57 (76%) had symptomatic SARS-CoV-2 infection. Regarding birth outcomes, 32 (41%) had cesarean delivery and 14 (19%) had preterm birth. Among 75 infants, 5 (7%) had positive SARS-CoV-2 polymerase chain reaction tests in the first week of life, all of whom were born to Hispanic mothers with symptomatic SARS-CoV-2 infection and had clinical courses consistent with gestational age. Six (8%) infants visited the emergency department within 30 days of discharge; one was admitted with a non-COVID-19 diagnosis. CONCLUSION: At our urban, safety-net hospital among pregnant women with positive SARS-CoV-2 tests, 41% had a cesarean delivery and 19% had a preterm birth. Seven percent of infants had one or more positive SARS-CoV-2 tests and all infants had clinical courses expected for gestational age. KEY POINTS: · Among 75 pregnant women with SARS-CoV-2 positive testing at our center, five infants (7%) had one or more SARS-CoV-2 positive tests in the first week of life.. · Infants with positive SARS-CoV-2 tests had clinical courses expected for gestational age..
Subject(s)
COVID-19 , Infant, Newborn, Diseases , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious , SARS-CoV-2/isolation & purification , Adult , Boston/epidemiology , COVID-19/epidemiology , COVID-19/therapy , COVID-19/transmission , Cesarean Section/statistics & numerical data , Female , Gestational Age , Hospitalization/statistics & numerical data , Humans , Infant Care/methods , Infant Care/statistics & numerical data , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical/prevention & control , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Pregnancy Outcome , Premature Birth/epidemiology , Safety-net Providers/statistics & numerical dataABSTRACT
Isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs, respectively) are plasticizers and flame retardants that are ubiquitous in indoor environments; however, no studies to date have characterized their metabolism. Using human liver subcellular S9 fractions, phase I and II in vitro metabolism of triphenyl phosphate (TPHP), 4-tert-butylphenyl diphenyl phosphate (4tBPDPP), 2-isopropylphenyl diphenyl phosphate (2IPPDPP), and 4-isopropylphenyl diphenyl phosphate (4IPPDPP) was investigated at 1 and 10 µM doses. Parent depletion and the formation of known or suspected metabolites (e.g., likely hydrolysis or hydroxylated products), including diphenyl phosphate (DPHP), hydroxyl-triphenyl phosphate (OH-TPHP), isopropylphenyl phenyl phosphate (ip-PPP), and tert-butylphenyl phenyl phosphate (tb-PPP), were monitored and quantified via GC/MS or LC-MS/MS. tb-PPP and its conjugates were identified as the major in vitro metabolites of 4tBPDPP and accounted for 71% and 49%, respectively, of the parent molecule that was metabolized during the incubation. While the mass balance between parents and metabolites was conserved for TPHP and 4tBPDPP, approximately 20% of the initial parent mass was unaccounted for after quantifying suspected metabolites of 2IPPDPP and 4IPPDPP that had authentic standards available. Two novel ITP metabolites, mono-isopropenylphenyl diphenyl phosphate and hydroxy-isopropylphenyl diphenyl phosphate, were tentatively identified by high-resolution mass spectrometry and screened for in recently collected human urine where mono-isopropenylphenyl diphenyl phosphate was detected in one of nine samples analyzed. This study provides insight into the biological fate of ITP and TBPP isomers in human tissues and is useful in identifying appropriate biomarkers of exposure to monitor, particularly in support of epidemiological studies.
Subject(s)
Environmental Pollutants/metabolism , Esters/metabolism , Flame Retardants/metabolism , Liver/metabolism , Organophosphates/metabolism , Plasticizers/metabolism , Subcellular Fractions/metabolism , Biotransformation , Child , Child, Preschool , Environmental Pollutants/urine , Esters/urine , Humans , Organophosphates/urineABSTRACT
Sites along the Elizabeth River are contaminated with polycyclic aromatic hydrocarbons (PAHs) from historical creosote production and other industrial processes. Previous studies have demonstrated that Atlantic killifish collected from sites throughout the Elizabeth River display resistance to the teratogenic effects of PAH-exposure in a manner commensurate with sediment PAH concentrations. The current study characterized various chemical pollutants in sediment and investigated the effects of aqueous sediment extracts from sites along the Elizabeth River to the cardiac development of Atlantic killifish embryos from fish collected from an uncontaminated reference site. Embryonic cardiac deformities were more prevalent after exposure to extracts from sites with high PAH loads. However, activation of cytochrome P4501A, a gene up-regulated by PAH-induction of the aryl hydrocarbon receptor and measured using an in ovo EROD assay, did not consistently increase with PAH concentrations. This work further characterizes sediments in the Elizabeth River, as well as provides insight into the evolutionary pressures at each ER site.
Subject(s)
Fundulidae/physiology , Geologic Sediments/chemistry , Polycyclic Aromatic Hydrocarbons/toxicity , Water Pollutants, Chemical/toxicity , Animals , Embryo, Nonmammalian/drug effects , Metals/toxicity , Polychlorinated Biphenyls/toxicity , Rivers , VirginiaABSTRACT
Although ecological flexibility has been well documented in fungi, it remains unclear how this flexibility can be exploited for pollutant degradation, especially in the Ascomycota phylum. In this work, we assess three mycostimulation amendments for their ability to induce degradation in Trichoderma harzanium, a model fungus previously isolated from a Superfund site contaminated with polycyclic aromatic hydrocarbons. The amendments used in the present study were selected based on the documented ecological roles of ascomycetes. Chitin was selected to simulate the parasitic ecological role while cellulose and wood were selected to mimic bulk soil and wood saprobic conditions, respectively. Each amendment was tested in liquid basal medium in 0.1 and 1% (w/v) suspensions. Both chitin and cellulose amendments were shown to promote anthracene degradation in T. harzanium with the 0.1% chitin amendment resulting in over 90% removal of anthracene. None of the targets monitored for gene expression were found to be upregulated suggesting alternate pathways may be used in T. harzanium. Overall, our data suggest that mycostimulation amendments can be improved by understanding the ecological roles of indigenous fungi. However, further research is needed to better estimate specific amendment requirements for a broader group of target fungi and follow up studies are needed to determine whether the trends observed herein translate to more realistic soil systems.
Subject(s)
Ascomycota/metabolism , Biodegradation, Environmental , Carbon/metabolism , Polycyclic Aromatic Hydrocarbons/metabolism , Trichoderma/metabolism , Anthracenes/analysis , Anthracenes/metabolism , Ascomycota/enzymology , Ascomycota/genetics , Bioreactors , Chitin/metabolism , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Fungal , Soil Microbiology , Soil Pollutants , Trichoderma/enzymology , Trichoderma/geneticsABSTRACT
Traditional cooking using biomass is associated with ill health, local environmental degradation, and regional climate change. Clean stoves (liquefied petroleum gas (LPG), biogas, and electric) are heralded as a solution, but few studies have demonstrated their environmental health benefits in field settings. We analyzed the impact of mainly biogas (as well as electric and LPG) stove use on social, environmental, and health outcomes in two districts in Odisha, India, where the Indian government has promoted household biogas. We established a cross-sectional observational cohort of 105 households that use either traditional mud stoves or improved cookstoves (ICS). Our multidisciplinary team conducted surveys, environmental air sampling, fuel weighing, and health measurements. We examined associations between traditional or improved stove use and primary outcomes, stratifying households by proximity to major industrial plants. ICS use was associated with 91% reduced use of firewood (p < 0.01), substantial time savings for primary cooks, a 72% reduction in PM2.5, a 78% reduction in PAH levels, and significant reductions in water-soluble organic carbon and nitrogen (p < 0.01) in household air samples. ICS use was associated with reduced time in the hospital with acute respiratory infection and reduced diastolic blood pressure but not with other health measurements. We find many significant gains from promoting rural biogas stoves in a context in which traditional stove use persists, although pollution levels in ICS households still remained above WHO guidelines.
Subject(s)
Air Pollution, Indoor , Biofuels , Air Pollution , Climate Change , Cooking , Cross-Sectional Studies , Humans , IndiaABSTRACT
Flame retardant (FR) chemicals have often been added to polyurethane foam to meet required state and federal flammability standards. However, some FRs (e.g., PBDEs and TDCIPP) are associated with health hazards and are now restricted from use in some regions. In addition, California's residential furniture flammability standard (TB-117) has undergone significant amendments over the past few years, and TDCIPP has been added to California's Proposition 65 list. These events have likely led to shifts in the types of FRs used, and the products to which they are applied. To provide more information on the use of FRs in products containing polyurethane foam (PUF), we established a screening service for the general public. Participants residing in the US were allowed to submit up to 5 samples from their household for analysis, free of charge, and supplied information on the product category, labeling, and year and state of purchase. Between February 2014 and June 2016, we received 1141 PUF samples for analysis from various products including sofas, chairs, mattresses, car seats and pillows. Of these samples tested, 52% contained a FR at levels greater than 1% by weight. Tris(1,3-dichloroisopropyl)phosphate (TDCIPP) was the most common FR detected in PUF samples, and was the most common FR detected in all product categories. Analysis of the data by purchasing date suggests that the use of TDCIPP decreased in recent years, paralleled with an increase in the use of TCIPP and a nonhalogenated aryl phosphate mixture we call "TBPP." In addition, we observed significant decreases in FR applications in furniture products and child car seats, suggesting the use of additive FRs in PUF may be declining, perhaps as a reflection of recent changes to TB-117 and Proposition 65. More studies are needed to determine how these changes in FR use relate to changes in exposure among the general population.
Subject(s)
Flame Retardants , Interior Design and Furnishings , Dust , Halogenated Diphenyl Ethers , Housing , HumansABSTRACT
Thyroid hormones are critical regulators of normal development and physiological functioning in all vertebrates. Radioimmunoassay (RIA) approaches have been the method of choice for measuring circulating levels of thyroid hormones in vertebrates. While sensitive, RIA-based approaches only allow for a single analyte measurement per assay, can lack concordance across platforms and laboratories, and can be prone to analytical interferences especially when used with fish plasma. Ongoing advances in liquid chromatography tandem mass spectrometry (LC/MS/MS) have led to substantial decreases in detection limits for thyroid hormones and other biomolecules in complex matrices, including human plasma. Despite these advances, current analytical approaches do not allow for the measurement of native thyroid hormone in teleost fish plasma by mass spectrometry and continue to rely on immunoassay. In this study, we developed a new method that allows for the rapid extraction and simultaneous measurement of total T4 (TT4) and total T3 (TT3) in low volumes (50 µL) of fish plasma by LC/MS/MS. Methods were optimized initially in plasma from rainbow trout (Oncorhynchus mykiss) and applied to plasma from other teleost fishes, including fathead minnows (Pimephales promelas), mummichogs (Fundulus heteroclitus), sockeye salmon (Oncorhynchus nerka), and coho salmon (Oncorhynchus kisutch). Validation of method performance with T4- and T3-spiked rainbow trout plasma at 2 and 4 ng/mL produced mean recoveries ranging from 82 to 95 % and 97 to 105 %, respectively. Recovery of (13)C12-T4 internal standard in plasma extractions was: 99 ± 1.8 % in rainbow trout, 85 ± 11 % in fathead minnow, 73 ± 5.0 % in mummichog, 73 ± 1.7 % in sockeye salmon, and 80 ± 8.4 % in coho salmon. While absolute levels of thyroid hormones measured in identical plasma samples by LC/MS/MS and RIA varied depending on the assay used, T4/T3 ratios were generally consistent across both techniques. Less variability was measured among samples subjected to LC/MS/MS suggesting a more precise estimate of thyroid hormone homeostasis in the species targeted. Overall, a sensitive and reproducible method was established that takes advantage of LC/MS/MS techniques to rapidly measure TT4 and TT3 with negligible interferences in low volumes of plasma across a variety of teleost fishes.
Subject(s)
Blood Chemical Analysis/methods , Chromatography, Liquid , Fishes , Spectrometry, Mass, Electrospray Ionization , Thyroid Hormones/blood , Animals , Limit of Detection , Molecular Structure , Time Factors , TroutABSTRACT
BACKGROUND: People are exposed to a variety of chemicals each day as a result of their personal care product (PCP) use. OBJECTIVE: This study was designed to determine if silicone wristbands provide a quantitative estimate of internal dose for phenols commonly associated with PCPs, with a focus on triclosan and four parabens: methyl-, ethyl-, propyl-, and butylparaben. Uptake of these compounds into wristbands and correlations with internal dose were assessed. METHODS: Ten adults from central North Carolina wore five silicone wristbands, with one wristband removed each day for 5 days. Each participant provided a 24 h urine sample and a random spot urine sample each day, in which paraben and triclosan metabolites were evaluated. RESULTS: All parabens and triclosan were detected frequently in wristbands and, except for butylparaben, in urine samples. Wristband and spot urine concentrations of parabens and triclosan were both compared to a measurement of internal dose (i.e., the total metabolite mass excreted over 5 days as a measurement of internal dose). IMPACT STATEMENT: The two most hydrophobic compounds investigated, butylparaben and triclosan, displayed significant linear uptake in wristbands over 5 days, whereas concentrations of methyl- and ethylparaben displayed a steady state concentration. In general, wristbands and spot urine samples were similarly correlated to internal dose for frequently detected parabens and triclosan. However, wristbands have additional advantages including higher detection rates and reduced participant burden that may make them more suitable tools for assessing exposure to PCPs.
Subject(s)
Environmental Exposure , Parabens , Silicones , Triclosan , Humans , Parabens/analysis , Triclosan/urine , Adult , Female , Male , Environmental Exposure/analysis , North Carolina , Middle Aged , Biological Monitoring/methods , Environmental Monitoring/methods , Wrist , Young Adult , CosmeticsABSTRACT
Due to differences in chemical properties and half-lives, best practices for exposure assessment may differ for legacy versus novel brominated flame retardants (BFRs). Our objective was to identify the environment matrix that best predicted biomarkers of children's BFR exposures. Paired samples were collected from children aged 3-6 years and their homes, including dust, a small piece of polyurethane foam from the furniture, and a handwipe and wristband from each child. Biological samples collected included serum, which was analyzed for 11 polybrominated diphenyl ethers (PBDEs), and urine, which was analyzed for tetrabromobenzoic acid (TBBA), a metabolite of 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). Significant positive correlations were typically observed between BFRs measured in dust, handwipes and wristbands, though wristbands and handwipes tended to be more strongly correlated with one another than with dust. PBDEs, EH-TBB and BEH-TEBP were detected in 30% of the sofa foam samples, suggesting that the foam was treated with PentaBDE or Firemaster® 550/600 (FM 550/600). PBDEs were detected in all serum samples and TBBA was detected in 43% of urine samples. Statistically significant positive correlations were observed between the environmental samples and serum for PBDEs. Urinary TBBA was 6.86 and 6.58 times more likely to be detected among children in the highest tertile of EH-TBB exposure for handwipes and wristbands, respectively (95 % CI: 2.61, 18.06 and 1.43, 30.05 with p < 0.001 and 0.02, respectively). The presence of either PentaBDE or FM 550/600 in furniture was also associated with significantly higher levels of these chemicals in dust, handwipes and serum (for PBDEs) and more frequent detection of TBBA in urine (p = 0.13). Our results suggest that children are exposed to a range of BFRs in the home, some of which likely originate from residential furniture, and that silicone wristbands are a practical tool for evaluating external exposure to both legacy and novel BFRs.
Subject(s)
Environmental Exposure , Flame Retardants , Halogenated Diphenyl Ethers , Flame Retardants/analysis , Humans , Halogenated Diphenyl Ethers/blood , Child , Child, Preschool , Environmental Exposure/statistics & numerical data , Environmental Exposure/analysis , Female , Male , Dust/analysis , Environmental Pollutants/urine , Environmental Pollutants/blood , Environmental Monitoring , Housing , Air Pollution, Indoor/statistics & numerical data , Air Pollution, Indoor/analysisABSTRACT
Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries Superfund Site (Elizabeth River, Portsmouth, VA, USA) are resistant to the acute toxicity and cardiac teratogenesis caused by high levels of polycyclic aromatic hydrocarbons (PAHs) from creosote. The resistance is linked to down regulation of the aryl hydrocarbon receptor (AHR) pathway. We investigated the association between CYP1 activity, as a marker of potential AHR pathway suppression, and contaminant resistance in killifish subpopulations from sites throughout the estuary that varied significantly in PAH contamination level. Adult killifish and sediments were collected from seven sites across approximately 13.7 km in river length within the estuary and from a nearby reference site. Sediment PAH levels were determined using gas chromatography mass spectrometry. Embryos obtained via manual spawning were exposed to individual AHR agonists and PAH mixtures 24 h post fertilization (hpf); CYP1 activity was determined by in ovo ethoxyresorufin-o-deethylase (EROD) at 96 hpf, and cardiac deformity severity was scored at 144 hpf. The total PAH levels measured among the sites varied from approximately 200 to 125,000 ng/g dry sediment. Overall, the resistance to teratogenesis was strongest in the subpopulations from sites in or closest to the major PAH contamination sites, but even embryos from less-contaminated sites within the Elizabeth River demonstrated at least partial resistance to many challenges. Surprisingly, all of the subpopulations tested were highly resistant to PCB-126 (3,3',4,4',5-pentachlorobiphenyl). However, the degree of CYP1 activity response varied significantly among subpopulations and did not always correlate strongly with resistance to teratogenesis; some subpopulations resisted the cardiac teratogenesis caused by the challenges at doses that still elicited strong EROD induction. Our results suggest that there is variation in the adaptive phenotype exhibited by laboratory-spawned embryos from killifish subpopulations throughout the estuary. Furthermore, the results show that contaminants have affected killifish subpopulations throughout the estuary, even in sites with lower levels of PAHs.
Subject(s)
Cytochrome P-450 CYP1A1/metabolism , Fundulidae/physiology , Polychlorinated Biphenyls/toxicity , Polycyclic Aromatic Hydrocarbons/toxicity , Teratogens/toxicity , Water Pollutants, Chemical/toxicity , Abnormalities, Drug-Induced/enzymology , Adaptation, Physiological , Animals , Embryo, Nonmammalian/abnormalities , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/enzymology , Embryonic Development/drug effects , Fundulidae/abnormalities , Geologic Sediments/analysis , Heart Defects, Congenital/chemically induced , Heart Defects, Congenital/enzymology , Polycyclic Aromatic Hydrocarbons/analysis , Receptors, Aryl Hydrocarbon/metabolism , Teratogens/analysis , Virginia , Water Pollutants, Chemical/analysisABSTRACT
With the phase-out of polybrominated diphenyl ether (PBDE) flame retardants, the use of new and alternate flame retardants has been increasing. 2,2-bis(chloromethyl)propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate, known as V6, is a flame retardant applied to polyurethane foam commonly found in furniture and automobile foam. However, to the authors' knowledge, no research has been conducted on V6 levels in the environment. The intention of this study was to measure the concentration of V6 in foam collected from baby products where it was recently detected and measure levels in dust samples collected from homes and automobiles in the Boston, MA area. To accomplish this, a pure V6 commercial standard was purchased from a Chinese manufacturer and purified (>98%). An analytical method to measure V6 in dust samples using liquid chromatography tandem mass spectrometry (LC/MS-MS) was developed. Extraction was conducted using accelerated solvent extraction (ASE) and extracts were purified using an ENVI-Florisil SPE column (500 mg, 3 mL). V6 was measured in foam samples collected from baby products with a concentration ranging from 24,500,000 to 59,500,000 ng/g of foam (n = 12, average ± sd: 46,500,000 ± 12,000,000 ng/g; i.e., on average, 4.6% of the foam mass was V6). V6 was also detected in 19 of 20 car dust samples and 14 of 20 house dust samples analyzed. The concentration of V6 in the house dust ranged from <5 ng/g to 1110 ng/g with a median of 12.5 ng/g, and <5 ng/g to 6160 ng/g in the car dust with a median of 103.0 ng/g. Concentrations in car dust were significantly higher than in the house dust potentially indicating higher use of V6 in automobiles compared to products found in the home. Furthermore, tris (2-chloroethyl) phosphate (TCEP), a known carcinogen, was found in the V6 commercial mixture (14% by weight) as an impurity and was consistently detected with V6 in the foam samples analyzed. A significant correlation was also observed between V6 and TCEP in the dust samples suggesting that the use of V6 is a significant source of TCEP in the indoor environment.
Subject(s)
Dust/analysis , Flame Retardants/analysis , Motor Vehicles , Residence Characteristics , Chromatography, Liquid , Tandem Mass SpectrometryABSTRACT
The potential for polycyclic aromatic hydrocarbons (PAHs) to have adverse effects that persist across generations is an emerging concern for human and wildlife health. This study evaluated the role of mitochondria, which are maternally inherited, in the cross-generational toxicity of benzo(a)pyrene (BaP), a model PAH and known mitochondrial toxicant. Mature female zebrafish (F0) were fed diets containing 0, 12.5, 125, or 1250 µg BaP/g at a feed rate of 1% body weight twice/day for 21 days. These females were bred with unexposed males, and the embryos (F1) were collected for subsequent analyses. Maternally-exposed embryos exhibited altered mitochondrial function and metabolic partitioning (i.e. the portion of respiration attributable to different cellular processes), as evidenced by in vivo oxygen consumption rates (OCRs). F1 embryos had lower basal and mitochondrial respiration and ATP turnover-mediated OCR, and increased proton leak and reserve capacity. Reductions in mitochondrial DNA (mtDNA) copy number, increases in mtDNA damage, and alterations in biomarkers of oxidative stress were also found in maternally-exposed embryos. Notably, the mitochondrial effects in offspring occurred largely in the absence of effects in maternal ovaries, suggesting that PAH-induced mitochondrial dysfunction may manifest in subsequent generations. Maternally-exposed larvae also displayed swimming hypoactivity. The lowest observed effect level (LOEL) for maternal BaP exposure causing mitochondrial effects in offspring was 12.5 µg BaP/g diet (nominally equivalent to 250 ng BaP/g fish). It was concluded that maternal BaP exposure can cause significant mitochondrial impairments in offspring.
ABSTRACT
BACKGROUND: We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1. METHODS: Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK, and HIV RNA were assessed through week 24. RESULTS: Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, were enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. The doravirine geometric mean (GM) AUC 0-∞ was 34.8 µMâhour, and the GM C 24 was 514 nM after a single dose, with a predicted steady-state GM C 24,ss,pred of 690 nM. Cohort 2 enrolled adolescents weighing ≥45 kg. Plasma concentrations of doravirine, tenofovir, and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI: [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL. CONCLUSIONS: Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well-tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV Seropositivity , HIV-1 , Adult , Humans , Adolescent , Child , Lamivudine/adverse effects , Lamivudine/pharmacokinetics , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , HIV Infections/drug therapy , Tenofovir/therapeutic use , Anti-Retroviral Agents/therapeutic use , Pyridones/therapeutic use , HIV Seropositivity/drug therapy , RNA, Viral , Tablets , Emtricitabine/therapeutic useABSTRACT
Firefighters are occupationally exposed to an array of hazardous chemicals, and these exposures have been linked to the higher rates of some cancer in firefighters. However, additional research that characterizes firefighters' exposure is needed to fully elucidate the impacts on health risks. In this pilot study, we used silicone wristbands to quantify off-duty and on-duty chemical exposures experienced by 20 firefighters in Durham, North Carolina. By using each firefighter's off-duty wristband to represent individual baseline exposures, we assessed occupation-related exposures (i.e. on-duty exposures). We also investigated the influence of responding to a fire event while on-duty. In total, 134 chemicals were quantified using both GC-MS and LC-MS/MS targeted methods. Seventy-one chemicals were detected in at least 50% of all silicone wristbands, including 7 PFAS, which to our knowledge, have not been reported in wristbands previously. Of these, phthalates were generally measured at the highest concentrations, followed by brominated flame retardants (BFRs) and organophosphate esters (OPEs). PFAS were measured at lower concentrations overall, but firefighter PFOS exposures while on-duty and responding to fires were 2.5 times higher than off-duty exposures. Exposure to polycyclic aromatic hydrocarbons (PAH), BFRs, and some OPEs were occupationally associated, with firefighters experiencing 0.5 to 8.5 times higher exposure while on-duty as compared to off-duty. PAH exposures were also higher for firefighters who respond to a fire than those who did not while on-duty. Additional research with a larger population of firefighters that builds upon this pilot investigation may further pinpoint exposure sources that may contribute to firefighters' risk for cancer, such as those from firefighter gear or directly from fires. This research demonstrates the utility of using silicone wristbands to quantify occupational exposure in firefighters and the ability to disentangle exposures that may be specific to fire events as opposed to other sources that firefighters might experience.
Subject(s)
Air Pollutants, Occupational , Firefighters , Fires , Flame Retardants , Fluorocarbons , Neoplasms , Occupational Exposure , Polycyclic Aromatic Hydrocarbons , Air Pollutants, Occupational/analysis , Chromatography, Liquid , Flame Retardants/analysis , Humans , Occupational Exposure/analysis , Organophosphates , Pilot Projects , Polycyclic Aromatic Hydrocarbons/analysis , Silicones , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Advances in medical treatments in recent years have contributed to an overall decline in HIV-related opportunistic infections and deaths in youth; however, mortality and morbidity rates in perinatally and nonperinatally infected adolescents and young adults (AYA) living with HIV remain relatively high today. OBJECTIVE: The goal of this project was to assess the use, utility, and cost-effectiveness of PlusCare, a digital app for HIV case management in AYA living with HIV. The app supports routine case management tasks, such as scheduling follow-up visits, sharing documents for review and signature, laboratory test results, and between-visit communications (eg, encouraging messages). METHODS: We conducted a single-group mixed methods pre-post study with HIV case management programs in 2 large urban hospitals in the Boston metro area. Case management staff (case managers [CMs], N=20) and AYA living with HIV participants (N=45) took part in the study with access to PlusCare for up to 15 and 12 months, respectively. RESULTS: The CMs and AYA living with HIV reported mean System Usability Scale scores of 51 (SD 7.9) and 63 (SD 10.6), respectively. Although marginally significant, total charges billed at 1 of the 2 sites compared with the 12 months before app use (including emergency, inpatient, and outpatient charges) decreased by 41% (P=.046). We also observed slight increases in AYA living with HIV self-reported self-efficacy in chronic disease management and quality of life (Health-Related Quality of Life-4) from baseline to the 12-month follow-up (P=.02 and P=.03, respectively) and increased self-efficacy from the 6- to 12-month follow-up (P=.02). There was no significant change in HIV viral suppression, appointment adherence, or medication adherence in this small-sample pilot study. CONCLUSIONS: Although perceived usability was low, qualitative feedback from CMs and use patterns suggested that direct messaging and timely, remote, and secure sharing of laboratory results and documents (including electronic signatures) between CMs and AYA living with HIV can be particularly useful and have potential value in supporting care coordination and promoting patient self-efficacy and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03758066; https://clinicaltrials.gov/ct2/show/NCT03758066.
ABSTRACT
With the phase-out of PentaBDE in 2004, alternative flame retardants are being used in polyurethane foam to meet flammability standards. However, insufficient information is available on the identity of the flame retardants currently in use. Baby products containing polyurethane foam must meet California state furniture flammability standards, which likely affects the use of flame retardants in baby products throughout the U.S. However, it is unclear which products contain flame retardants and at what concentrations. In this study we surveyed baby products containing polyurethane foam to investigate how often flame retardants were used in these products. Information on when the products were purchased and whether they contained a label indicating that the product meets requirements for a California flammability standard were recorded. When possible, we identified the flame retardants being used and their concentrations in the foam. Foam samples collected from 101 commonly used baby products were analyzed. Eighty samples contained an identifiable flame retardant additive, and all but one of these was either chlorinated or brominated. The most common flame retardant detected was tris(1,3-dichloroisopropyl) phosphate (TDCPP; detection frequency 36%), followed by components typically found in the Firemaster550 commercial mixture (detection frequency 17%). Five samples contained PBDE congeners commonly associated with PentaBDE, suggesting products with PentaBDE are still in-use. Two chlorinated organophosphate flame retardants (OPFRs) not previously documented in the environment were also identified, one of which is commercially sold as V6 (detection frequency 15%) and contains tris(2-chloroethyl) phosphate (TCEP) as an impurity. As an addition to this study, we used a portable X-ray fluorescence (XRF) analyzer to estimate the bromine and chlorine content of the foam and investigate whether XRF is a useful method for predicting the presence of halogenated flame retardant additives in these products. A significant correlation was observed for bromine; however, there was no significant relationship observed for chlorine. To the authors knowledge, this is the first study to report on flame retardants in baby products. In addition, we have identified two chlorinated OPFRs not previously documented in the environment or in consumer products. Based on exposure estimates conducted by the Consumer Product Safety Commission (CPSC), we predict that infants may receive greater exposure to TDCPP from these products compared to the average child or adult from upholstered furniture, all of which are higher than acceptable daily intake levels of TDCPP set by the CPSC. Future studies are therefore warranted to specifically measure infants exposure to these flame retardants from intimate contact with these products and to determine if there are any associated health concerns.
Subject(s)
Environmental Monitoring/methods , Flame Retardants/analysis , Infant Equipment , Polyurethanes/chemistry , Bromine/analysis , Chlorine/analysis , Environmental Health , Gas Chromatography-Mass Spectrometry , Humans , Infant , Polybrominated Biphenyls/chemistry , Spectrometry, X-Ray EmissionABSTRACT
Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention.
Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Anti-HIV Agents/therapeutic use , Child , Emergency Service, Hospital , HIV , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Post-Exposure ProphylaxisABSTRACT
In this study, we sought to expand our previous research on associations between bioactivities in dust and associated organic contaminants. Dust samples were collected from central NC homes (n = 188), solvent extracted, and split into two fractions, one for analysis using three different bioassays (nuclear receptor activation/inhibition and adipocyte development) and one for mass spectrometry (targeted measurement of 124 organic contaminants, including flame retardants, polychlorinated biphenyls, perfluoroalkyl substances, pesticides, phthalates, and polycyclic aromatic hydrocarbons). Approximately 80% of dust extracts exhibited significant adipogenic activity at concentrations that are comparable to estimated exposure for children and adults (e.g. ~20 µg/well dust) via either triglyceride accumulation (65%) and/or pre-adipocyte proliferation (50%). Approximately 76% of samples antagonized thyroid receptor beta (TRß), and 21% activated peroxisome proliferator activated receptor gamma (PPARγ). Triglyceride accumulation was significantly correlated with TRß antagonism. Sixty-five contaminants were detected in at least 75% of samples; of these, 26 were correlated with adipogenic activity and ten with TRß antagonism. Regression models were used to evaluate associations of individual contaminants with adipogenic and TRß bioactivities, and many individual contaminants were significantly associated. An exploratory g-computation model was used to evaluate the effect of mixtures. Contaminant mixtures were positively associated with triglyceride accumulation, and the magnitude of effect was larger than for any individually measured chemical. For each quartile increase in mixture exposure, triglyceride accumulation increased by 212% (RR = 3.12 and 95% confidence interval: 1.58, 6.17). These results suggest that complex mixtures of chemicals present in house dust may induce adipogenic activity in vitro at environmental concentrations and warrants further research.
Subject(s)
Air Pollution, Indoor , Flame Retardants , PPAR gamma , Thyroid Hormone Receptors beta , Adult , Air Pollution, Indoor/analysis , Child , Dust , Flame Retardants/analysis , Flame Retardants/toxicity , Humans , PPAR gamma/metabolism , Plant Extracts , Thyroid Hormone Receptors beta/metabolismABSTRACT
OBJECTIVE: The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS). METHODS: We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020. RESULTS: Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two. CONCLUSION: Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.