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1.
Nano Lett ; 24(23): 6844-6849, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38804726

RESUMO

Programmable photonic integrated circuits (PICs) are an increasingly important platform in optical science and engineering. However, current programmable PICs are mostly formed through subtractive fabrication techniques, which limits the reconfigurability of the device and makes prototyping costly and time-consuming. A rewritable PIC architecture can circumvent these drawbacks, where PICs are repeatedly written and erased on a single PIC canvas. We demonstrate such a rewritable PIC platform by selective laser writing a layer of wide-band-gap phase change material (PCM) Sb2S3 with a low-cost benchtop setup. We show arbitrary patterning with resolution up to 300 nm and write dielectric assisted waveguides with a low optical loss of 0.0172 dB/µm. We envision that using this inexpensive benchtop platform thousands of PIC designs can be written, tested, and erased on the same chip without the need for lithography/etching tools or a nanofabrication facility, thus reducing manufacturing cost and increasing accessibility.

2.
Environ Sci Technol ; 58(19): 8264-8277, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691655

RESUMO

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.


Assuntos
Fluorocarbonos , Lipídeos , Humanos , Feminino , Gravidez , Lipídeos/sangue , Fluorocarbonos/sangue , Saúde da Criança , Estudos de Coortes , Estudos Transversais , Adulto , Poluentes Ambientais/sangue , Exposição Ambiental , Exposição Materna , Criança
3.
Environ Res ; 250: 118434, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38346483

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. METHODS: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. RESULTS: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. IMPLICATIONS: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings.


Assuntos
Biomarcadores , Fluorocarbonos , Humanos , Feminino , Gravidez , Fluorocarbonos/sangue , Adulto , Biomarcadores/sangue , Adulto Jovem , Poluentes Ambientais/sangue , Inflamação/induzido quimicamente , Inflamação/sangue , Estudos Transversais , Exposição Materna/efeitos adversos
4.
Public Health Nurs ; 41(4): 704-708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745505

RESUMO

OBJECTIVE: Our goal is to examine gaps in self-carry, asthma emergency protocol, and stock inhaler policy knowledge in Illinois schools. DESIGN: A 30-item REDCap cross-sectional survey developed by a team of stakeholders was disseminated. Questions assessed policy knowledge, awareness, and practices regarding asthma emergency protocols, self-carry, and stock inhalers. SAMPLE: Participants were Illinois school nurses belonging to a governmental organization listserv. MEASUREMENTS: Analysis utilized Chi-square tests, descriptive statistics, and t-tests. RESULTS: Nurses reported 36% of students on average self-carried asthma medication. Thirty percent of nurses were not aware of their emergency asthma policy and only 60% reported having an emergency asthma protocol in their school(s). Fifty-four percent of nurses were aware of stock inhaler programming. Of the 10.3% who reported a stock inhaler program, a lower frequency reported calling 911 for asthma emergencies. Perceived school asthma prevalence varied from 0%-87%. CONCLUSIONS: Our survey demonstrates large variation in knowledge and implementation of school-based asthma health policy. This is likely due to variations in health policy education dissemination. Future efforts should focus on the dissemination and implementation of school-based asthma health policies to improve their more universal adoption and better support school-based asthma management.


Assuntos
Asma , Política de Saúde , Serviços de Enfermagem Escolar , Humanos , Asma/tratamento farmacológico , Asma/enfermagem , Illinois/epidemiologia , Estudos Transversais , Inquéritos e Questionários , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Masculino , Criança , Adulto , Serviços de Saúde Escolar/organização & administração , Nebulizadores e Vaporizadores
5.
Opt Lett ; 48(9): 2385-2388, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126279

RESUMO

Photonic integrated circuits (PICs) can drastically expand the capabilities of quantum and classical optical information science and engineering. PICs are commonly fabricated using selective material etching, a subtractive process. Thus, the chip's functionality cannot be substantially altered once fabricated. Here, we propose to exploit wide-bandgap non-volatile phase-change materials (PCMs) to create rewritable PICs. A PCM-based PIC can be written using a nanosecond pulsed laser without removing any material, akin to rewritable compact disks. The whole circuit can then be erased by heating, and a new circuit can be rewritten. We designed a dielectric-assisted PCM waveguide consisting of a thick dielectric layer on top of a thin layer of wide-bandgap PCMs Sb2S3 and Sb2Se3. The low-loss PCMs and our designed waveguides lead to negligible optical loss. Furthermore, we analyzed the spatiotemporal laser pulse shape to write the PICs. Our proposed platform will enable low-cost manufacturing and have a far-reaching impact on the rapid prototyping of PICs, validation of new designs, and photonic education.

6.
Am J Obstet Gynecol ; 228(5): 576.e1-576.e22, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36400174

RESUMO

BACKGROUND: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States. OBJECTIVE: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin. STUDY DESIGN: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models. RESULTS: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis. CONCLUSION: Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.


Assuntos
Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Criança , Estados Unidos/epidemiologia , Nascimento Prematuro/epidemiologia , Dinoprosta/urina , Estresse Oxidativo , Biomarcadores/metabolismo , Avaliação de Resultados em Cuidados de Saúde
7.
Pediatr Res ; 93(5): 1285-1293, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34916626

RESUMO

BACKGROUND: This study examined the relationship between prenatal maternal stress (PREMS) and non-nutritive suck (NNS) and tested its robustness across 2 demographically diverse populations. METHODS: The study involved 2 prospective birth cohorts participating in the national Environmental influences on Child Health Outcomes (ECHO) Program: Illinois Kids Development Study (IKIDS) and ECHO Puerto Rico (ECHO-PROTECT). PREMS was measured during late pregnancy via the 10-item Perceived Stress Scale (PSS-10). NNS was sampled from 1- to 8-week-olds using a custom pacifier for ~5 min. RESULTS: Overall, 237 mother-infant dyads completed this study. Despite several significant differences, including race/ethnicity, income, education, and PREMS levels, significant PREMS-NNS associations were found in the 2 cohorts. In adjusted linear regression models, higher PREMS, measured through PSS-10 total scores, related to fewer but longer NNS bursts per minute. CONCLUSIONS: A significant association was observed between PREMS and NNS across two diverse cohorts. This finding is important as it may enable the earlier detection of exposure-related deficits and, as a result, earlier intervention, which potentially can optimize outcomes. More research is needed to understand how NNS affects children's neurofunction and development. IMPACT: In this double-cohort study, we found that higher maternal perceived stress assessed in late pregnancy was significantly associated with fewer but longer sucking bursts in 1- to 8-week-old infants. This is the first study investigating the association between prenatal maternal stress (PREMS) and infant non-nutritive suck (NNS), an early indicator of central nervous system integrity. Non-nutritive suck is a potential marker of increased prenatal stress in diverse populations. Non-nutritive suck can potentially serve as an early indicator of exposure-related neuropsychological deficits allowing for earlier interventions and thus better prognoses.


Assuntos
Mães , Comportamento de Sucção , Feminino , Criança , Humanos , Lactente , Gravidez , Estudos de Coortes , Estudos Prospectivos , Comportamento de Sucção/fisiologia , Chupetas
8.
Pediatr Res ; 94(6): 2085-2091, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37479746

RESUMO

BACKGROUND: We aimed to understand the association between maternal stress in the first year of life and childhood body mass index (BMI) from 2 to 4 years of age in a large, prospective United States-based consortium of cohorts. METHODS: We used data from the Environmental influences on Child Health Outcomes program. The main exposure was maternal stress in the first year of life measured with the Perceived Stress Scale (PSS). The main outcome was the first childhood BMI percentile after age 2 until age 4 years. We used an adjusted linear mixed effects model to examine associations between BMI and PSS quartile. RESULTS: The mean BMI percentile in children was 59.8 (SD 30) measured at 3.0 years (SD 1) on average. In both crude models and models adjusted for maternal BMI, age, race, ethnicity, infant birthweight, and health insurance status, no linear associations were observed between maternal stress and child BMI. CONCLUSIONS: Among 1694 maternal-infant dyads, we found no statistically significant relationships between maternal perceived stress in the first year of life and child BMI after 2 through 4 years. IMPACT: Although existing literature suggests relationships between parental stress and childhood BMI, we found no linear associations between maternal stress in the first year of life and childhood BMI at 2-4 years of age among participants in ECHO cohorts. Higher maternal stress was significantly associated with Hispanic ethnicity, Black race, and public health insurance. Our analysis of a large, nationally representative sample challenges assumptions that maternal stress in the first year of life, as measured by a widely used scale, is associated with offspring BMI.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Lactente , Humanos , Criança , Pré-Escolar , Estados Unidos/epidemiologia , Índice de Massa Corporal , Estudos Prospectivos , Fatores de Risco , Peso ao Nascer
9.
Environ Res ; 219: 115057, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36529335

RESUMO

BACKGROUND: Previous studies have indicated that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), when used as an alternative to per- and polyfluoroalkyl substances (PFASs), result in kidney toxicity. However, their co-exposure with heavy metals, has not yet been described. OBJECTIVES: To explore the joint effects of Cl-PFESAs and heavy metal exposure on renal health in Chinese adults, and identify specific pollutants driving the associations. METHODS: Our sample consists of 1312 adults from a cross-sectional survey of general communities in Guangzhou, China. We measured Cl-PFESAs, legacy PFASs (perfluorooctanoic acid [PFOA] and perfluorooctane sulfonated [PFOS]), and heavy metals (arsenic, cadmium, and lead). The relationship between single pollutant and glomerular filtration rate (eGFR) and the odds ratio (OR) of chronic kidney disease (CKD) was studied using Generalized additive models (GAMs). Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint effects of Cl-PFESAs and heavy metals. Additionally, we conducted a sex-specific analysis to determine the modification effect of this variable. RESULTS: In single pollutant models, CI-PFESAs, PFOA, PFOS and arsenic were negatively associated with eGFR. Additionally, PFOA and heavy metals were positively correlated with the OR of CKD. For example, the estimated change with 95% confidence intervals (CI) of eGFR at from the highest quantile of 6:2 Cl-PFESA versus the lowest quantile was -5.65 ng/mL (95% CI: -8.21, -3.10). Sex played a role in modifying the association between 8:2 Cl-PFESA, PFOS and eGFR. In BKMR models, pollutant mixtures had a negative joint association with eGFR and a positive joint effect on CKD, especially in women. Arsenic appeared to be the primary contributing pollutant. CONCLUSION: We provide epidemiological evidence that Cl-PFESAs independently and jointly with heavy metals impaired kidney health. More population-based human and animal studies are needed to confirm our results.


Assuntos
Ácidos Alcanossulfônicos , Arsênio , Poluentes Ambientais , Fluorocarbonos , Insuficiência Renal Crônica , Adulto , Animais , Feminino , Humanos , Ácidos Alcanossulfônicos/análise , Arsênio/toxicidade , Arsênio/análise , Estudos Transversais , Teorema de Bayes , Ácidos Sulfônicos/análise , Éteres , Éter , China/epidemiologia , Alcanossulfonatos/análise , Poluentes Ambientais/toxicidade , Poluentes Ambientais/análise , Fluorocarbonos/toxicidade , Fluorocarbonos/análise , Cádmio/análise , Rim
10.
Environ Sci Technol ; 56(10): 6152-6161, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35380809

RESUMO

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Alcanossulfonatos , Animais , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Éter , Éteres , Fluorocarbonos/análise , Glândula Tireoide , Hormônios Tireóideos , Tireotropina
11.
Environ Res ; 212(Pt A): 113173, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35351450

RESUMO

Participants in biomonitoring studies who receive personal exposure reports seek information to reduce exposures. Many chemical exposures are driven by systems-level policies rather than individual actions; therefore, change requires engagement in collective action. Participants' perceptions of collective action and use of report-back to support engagement remain unclear. We conducted virtual focus groups during summer 2020 in a diverse group of peripartum people from cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program (N = 18). We assessed baseline exposure and collective action experience, and report-back preferences. Participants were motivated to protect the health of their families and communities despite significant time and cognitive burdens. They requested time-conscious tactics and accessible information to enable action to reduce individual and collective exposures. Participant input informed the design of digital report-back in the cohorts. This study highlights opportunities to shift responsibility from individuals to policymakers to reduce chemical exposures at the systems level.


Assuntos
Exposição Ambiental , Monitoramento Ambiental , Criança , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Grupos Focais , Humanos , Período Periparto
12.
Proc Natl Acad Sci U S A ; 115(36): E8460-E8468, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30127006

RESUMO

A variety of innate immune responses and functions are dependent on time of day, and many inflammatory conditions are associated with dysfunctional molecular clocks within immune cells. However, the functional importance of these innate immune clocks has yet to be fully characterized. NRF2 plays a critical role in the innate immune system, limiting inflammation via reactive oxygen species (ROS) suppression and direct repression of the proinflammatory cytokines, IL-1ß and IL-6. Here we reveal that the core molecular clock protein, BMAL1, controls the mRNA expression of Nrf2 via direct E-box binding to its promoter to regulate its activity. Deletion of Bmal1 decreased the response of NRF2 to LPS challenge, resulting in a blunted antioxidant response and reduced synthesis of glutathione. ROS accumulation was increased in Bmal1-/- macrophages, facilitating accumulation of the hypoxic response protein, HIF-1α. Increased ROS and HIF-1α levels, as well as decreased activity of NRF2 in cells lacking BMAL1, resulted in increased production of the proinflammatory cytokine, IL-1ß. The excessive prooxidant and proinflammatory phenotype of Bmal1-/- macrophages was rescued by genetic and pharmacological activation of NRF2, or through addition of antioxidants. Our findings uncover a clear role for the molecular clock in regulating NRF2 in innate immune cells to control the inflammatory response. These findings provide insights into the pathology of inflammatory conditions, in which the molecular clock, oxidative stress, and IL-1ß are known to play a role.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fatores de Transcrição ARNTL/genética , Animais , Células HEK293 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Interleucina-1beta/genética , Lipopolissacarídeos/toxicidade , Macrófagos/patologia , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo
13.
J Public Health Manag Pract ; 27(6): 567-576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33252372

RESUMO

CONTEXT: Millions of US homes receive water from private wells, which are not required to be tested for lead (Pb). An approach to prioritizing high-risk homes for water lead level (WLL) testing may help focus outreach and screening efforts, while reducing the testing of homes at low risk. OBJECTIVE: To (1) characterize distribution of WLLs and corrosivity in tap water of homes with private residential wells, and (2) develop and evaluate a screening strategy for predicting Pb detection within a home. DESIGN: Cross-sectional. SETTING: Three Illinois counties: Kane (northern), Peoria (central), and Jackson (southern). PARTICIPANTS: 151 private well users from 3 Illinois counties. INTERVENTION: Water samples were analyzed for WLL and corrosivity. MAIN OUTCOME MEASURES: (1) WLL and corrosivity, and (2) the sensitivity, specificity, and predictive value of a strategy for prioritizing homes for WLL testing. RESULTS: Pb was detected (>0.76 ppb) in tap water of 48.3% homes, and 3.3% exceeded 15 ppb, the US Environmental Protection Agency action level for community water systems. Compared with homes built in/after 1987 with relatively low corrosivity, older homes with more corrosive water were far more likely to contain measurable Pb (odds ratio = 11.07; 95% confidence interval, 3.47-35.31). The strategy for screening homes with private wells for WLL had a sensitivity of 88%, specificity of 42%, positive predictive value of 58%, and negative predictive value of 80%. CONCLUSIONS: Pb in residential well water is widespread. The screening strategy for prioritizing homes with private wells for WLL testing is greater than 85% sensitive.


Assuntos
Água Potável , Poluentes Químicos da Água , Estudos Transversais , Humanos , Chumbo , Poluentes Químicos da Água/análise , Abastecimento de Água , Poços de Água
14.
Immunology ; 157(2): 122-136, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30773630

RESUMO

Innate immune responses vary in a circadian manner, and more recent investigations aim to understand the underlying molecular mechanisms. Cytokine production varies significantly over the course of a day depending on the time of stimulation by pathogens or Toll-like receptor ligands, and multiple signaling pathways linked to the cell-autonomous circadian clock modulate innate immunity. Recognition of foreign material, especially by innate immune cells, engages a myriad of receptors, which trigger inflammatory responses, as well as endocytosis and degradation and/or processing for antigen presentation. Because of the close connection between particle engulfment and inflammation, it has been proposed that phagocytic uptake may drive cytokine production in phagocytes. Here we show that bacterial particle ingestion by mouse peritoneal macrophages displays temporal variation, but is independent of the cell-intrinsic circadian clock in an ex vivo setting. Although cytokine production is dependent on phagocytosis, uptake capacity across 12 hr does not translate into 24-hr rhythms in cytokine production. In vivo, time-of-day variations in phagocytic capacity are not found, whereas a time of day and clock-dependent cytokine response is maintained. These data show that efficiency of bacterial phagocytosis and the 24-hr rhythmicity of cytokine production by macrophages are independent of one another and should be studied separately.


Assuntos
Relógios Circadianos/imunologia , Citocinas/imunologia , Macrófagos Peritoneais/imunologia , Fagocitose , Animais , Macrófagos Peritoneais/citologia , Camundongos , Camundongos Knockout
15.
J Biol Chem ; 292(29): 12153-12164, 2017 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-28584055

RESUMO

Twenty-four hours of fasting is known to blunt activation of the human NLRP3 inflammasome. This effect might be mediated by SIRT3 activation, controlling mitochondrial reactive oxygen species. To characterize the molecular underpinnings of this fasting effect, we comparatively analyzed the NLRP3 inflammasome response to nutrient deprivation in wild-type and SIRT3 knock-out mice. Consistent with previous findings for human NLRP3, prolonged fasting blunted the inflammasome in wild-type mice but not in SIRT3 knock-out mice. In SIRT3 knock-out bone marrow-derived macrophages, NLRP3 activation promoted excess cytosolic extrusion of mitochondrial DNA along with increased reactive oxygen species and reduced superoxide dismutase 2 (SOD2) activity. Interestingly, the negative regulatory effect of SIRT3 on NLRP3 was not due to transcriptional control or priming of canonical inflammasome components but, rather, occurred via SIRT3-mediated deacetylation of mitochondrial SOD2, leading to SOD2 activation. We also found that siRNA knockdown of SIRT3 or SOD2 increased NLRP3 supercomplex formation and activation. Moreover, overexpression of wild-type and constitutively active SOD2 similarly blunted inflammasome assembly and activation, effects that were abrogated by acetylation mimic-modified SOD2. Finally, in vivo administration of lipopolysaccharide increased liver injury and the levels of peritoneal macrophage cytokines, including IL-1ß, in SIRT3 KO mice. These results support the emerging concept that enhancing mitochondrial resilience against damage-associated molecular patterns may play a pivotal role in preventing inflammation and that the anti-inflammatory effect of fasting-mimetic diets may be mediated, in part, through SIRT3-directed blunting of NLRP3 inflammasome assembly and activation.


Assuntos
Jejum , Inflamassomos/metabolismo , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Acetilação/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Linhagem Celular , Células Cultivadas , Ativação Enzimática , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Lipopolissacarídeos/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Multimerização Proteica/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Interferência de RNA , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/química
16.
Proc Natl Acad Sci U S A ; 112(23): 7231-6, 2015 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-25995365

RESUMO

The response to an innate immune challenge is conditioned by the time of day, but the molecular basis for this remains unclear. In myeloid cells, there is a temporal regulation to induction by lipopolysaccharide (LPS) of the proinflammatory microRNA miR-155 that correlates inversely with levels of BMAL1. BMAL1 in the myeloid lineage inhibits activation of NF-κB and miR-155 induction and protects mice from LPS-induced sepsis. Bmal1 has two miR-155-binding sites in its 3'-UTR, and, in response to LPS, miR-155 binds to these two target sites, leading to suppression of Bmal1 mRNA and protein in mice and humans. miR-155 deletion perturbs circadian function, gives rise to a shorter circadian day, and ablates the circadian effect on cytokine responses to LPS. Thus, the molecular clock controls miR-155 induction that can repress BMAL1 directly. This leads to an innate immune response that is variably responsive to challenges across the circadian day.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Ritmo Circadiano , Imunidade Inata , Macrófagos/imunologia , MicroRNAs/fisiologia , Regiões 3' não Traduzidas , Fatores de Transcrição ARNTL/genética , Tecido Adiposo/metabolismo , Animais , Citocinas/biossíntese , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo
17.
Environ Res ; 159: 158-163, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28802206

RESUMO

BACKGROUND: Studies have reported an association between serum perfluoroalkyl substances (PFASs) and asthma. However, few studies have examined the possible associations between PFASs and the 16-kDa club cell secretory protein (Clara) (CC16) level, a prominent biomarker of asthma, among adolescents. METHODS: We recruited a total of 231 asthmatic children and 225 non-asthmatic controls in the Genetic and Biomarkers study for Childhood Asthma (GBCA) in northern Taiwan from 2009 to 2010. Structured questionnaires were administered by face-to-face interview. Urine CC16 was determined by an enzyme-link immunoassay kit. Multiple general linear models were employed to examine the associations between PFASs and urinary CC16 levels. RESULTS: Asthmatic participants had significantly higher serum PFAS concentrations overall than the healthy controls. After adjusting for confounding factors, urinary CC16 was significantly, negatively associated with PFASs, especially PFOS, PFOA, PFDA and PFNA, and especially among males, as follows: PFOS (ß = -0.003, 95% confidence interval [CI]: -0.004, -0.002), PFOA (ß = -0.045, 95% CI: -0.086, -0.004), and PFHxA (ß = -0.310, 95% CI: -0.455, -0.165) among asthmatic boys, and PFDA (ß = -0.126, 95%CI: -0.241, -0.012) and PFNA (ß = -0.329, 95% CI: -0.526, -0.132) among non-asthmatic boys. Among girls, PFDA (ß = -0.088, 95% CI: -0.172, -0.004), was the only PFAS significantly associated with CC16. Significant interaction effects (p < 0.15) on CC16 levels were found between asthma and PFOS, PFOA, PFBS and PFHxA in all participants. CONCLUSION: Our overall results showed that serum PFASs were significantly, inversely associated with CC16 levels. Associations were stronger among males.


Assuntos
Ácidos Alcanossulfônicos/sangue , Asma/metabolismo , Exposição Ambiental , Poluentes Ambientais/sangue , Fluorocarbonos/sangue , Uteroglobina/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Taiwan , Uteroglobina/metabolismo
18.
Environ Res ; 155: 15-21, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28171771

RESUMO

Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.


Assuntos
Asma/fisiopatologia , Poluentes Ambientais/sangue , Fluorocarbonos/sangue , Pulmão/fisiopatologia , Adolescente , Asma/sangue , Asma/epidemiologia , Estudos de Casos e Controles , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/efeitos adversos , Feminino , Fluorocarbonos/efeitos adversos , Humanos , Masculino , Testes de Função Respiratória , Taiwan/epidemiologia
19.
J Community Health ; 42(2): 369-376, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27798746

RESUMO

Motivated by compelling, but scant, literature on high rates of breast cancer mortality among the United States Amish, a survey was conducted to examine mammography-seeking practices among Amish women. Inclusion criteria included age 40-70 years and membership of the Arthur, Illinois Amish community. Data were collected from this unique, socially isolated group through a mail questionnaire focusing on health history, mammography practices, and beliefs surrounding breast health. Sample mammography adherence and "ever mammogram" rates were compared with both the general population of the United States (U.S.) and other Amish communities in the U.S. Logistic regression on the "ever mammogram" variable showed that Amish women with knowledge of screening guidelines experienced an adjusted odds ratio (OR) of 5.26 [confidence interval (CI) 1.79, 15.45] for mammography screening compared to those without that knowledge. Participants who believed nutrition/diet causes breast cancer experienced an OR of 4.27 (CI 1.39, 13.11) for mammography and those who believed physical injury caused breast cancer had an OR of 3.86 (CI 1.24, 12.04) compared to women who do not hold these beliefs. Future research is needed to confirm and extend these results.


Assuntos
Amish/estatística & dados numéricos , Mamografia/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adulto , Idoso , Amish/psicologia , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Illinois , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Inquéritos e Questionários
20.
J Public Health Manag Pract ; 23(4): 396-403, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26910864

RESUMO

CONTEXT: Extreme heat waves elevate the population's risk for heat-related morbidity and mortality, specifically for vulnerable groups such as older adults and young children. In this context, we developed 2 Heat Vulnerability Indices (HVIs), one for the state of Wisconsin and one for the Milwaukee metropolitan area. OBJECTIVE: Through the creation of an HVI, state and local agencies will be able to use the indices as a planning tool for extreme heat events. DESIGN: Data used for the HVIs were grouped into 4 categories: (1) population density; (2) health factors; (3) demographic and socioeconomic factors; and (4) natural and built environment factors. These categories were mapped at the Census block group level. MAIN OUTCOME MEASURES: Unweighted z-score data were used to determine index scores, which were then mapped by quantiles ranging from "high" to "low" vulnerability. RESULTS: Statewide, Menominee County exhibited the highest vulnerability to extreme heat. Milwaukee HVI findings indicated high vulnerability in the city's inner core versus low vulnerability along the lakeshore. CONCLUSION: Visualization of vulnerability could help local public health agencies prepare for future extreme heat events.


Assuntos
Mapeamento Geográfico , Raios Infravermelhos/efeitos adversos , Populações Vulneráveis/estatística & dados numéricos , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Fatores de Risco , Fatores Socioeconômicos , Wisconsin
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