Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 Î¼m and smaller than 0.5 Î¼m (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/Âµl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.

Project description:ImportanceLimited availability of inpatient pediatric services in rural regions has raised concerns about access, safety, and quality of hospital-based care for children. This may be particularly important for children with medical complexity (CMC).ObjectivesTo describe differences in the availability of pediatric services at acute care hospitals where rural- and urban-residing CMC presented for hospitalization; identify rural-urban disparities in health care quality and in-hospital mortality; and determine whether the availability of pediatric services at index hospitals or the experience of interfacility transfer modified rural-urban differences in outcomes.Design, setting, and participantsThis retrospective cohort study examined all-payer claims data from Colorado, Massachusetts, and New Hampshire from 2012 to 2017. Analysis was conducted from May 2023 to July 2024. Participants included CMC younger than 18 years residing in these states and hospitalized during the study period.ExposuresRural or urban residence was determined using Rural-Urban Commuting Area codes. Hospitals were categorized as children's hospitals or general hospitals with comprehensive, limited, or no dedicated pediatric services using American Hospital Association survey data. Interfacility transfers between index and definitive care hospitals were identified using health care claims.Main outcomes and measuresIn-hospital mortality, all-cause 30-day readmission, medical-surgical safety events, and surgical safety events were operationalized using Agency for Healthcare Research and Quality measure specifications.ResultsAmong 36 943 CMC who experienced 79 906 hospitalizations, 16 525 (44.7%) were female, 26 034 (70.5%) were Medicaid-insured, and 34 008 (92.1%) were urban-residing. Rural-residing CMC were 6.55 times more likely to present to hospitals without dedicated pediatric services (rate ratio [RR], 6.55 [95% CI, 5.86-7.33]) and 2.03 times more likely to present to hospitals without pediatric beds (RR, 2.03 [95% CI, 1.88-2.21]) than urban-residing CMC, with no significant differences in interfacility transfer rates. In unadjusted analysis, rural-residing CMC had a 44% increased risk of in-hospital mortality (RR, 1.44 [95% CI, 1.03-2.02]) with no significant differences in other outcomes. Adjusting for clinical characteristics, the difference in in-hospital mortality was no longer significant. Index hospital type was not a significant modifier of observed rural-urban outcomes, but interfacility transfer was a significant modifier of rural-urban differences in surgical safety events.Conclusions and relevanceIn this cohort study, rural-residing CMC were significantly more likely to present to hospitals without dedicated pediatric services. These findings suggest that efforts are justified to ensure that all hospital types are prepared to care for CMC.

Project description:BackgroundRural patients have unique health-care factors influencing outcomes of arthroplasty, hypothetically putting these patients at increased risk for complications following total joint arthroplasty. The aim of this study is to better understand differences in patient outcomes and satisfaction between rural and urban patients receiving care in an urban setting and to provide more equitable care.MethodsA retrospective chart review was performed on patients undergoing primary total hip arthroplasty at a single large academic center between January 2013 and August 2020. Demographic, operative, and hospital outcomes were obtained from the institutional electronic medical record. Rurality was determined by rural-urban code (RUC) classifications by zip code with RUC codes 1-3 defined as urban and RUC 4-10 defined as rural.ResultsPatients from urban areas were more likely to visit the emergency department within 30 days postoperatively (P = .006) and be readmitted within 90 days (P < .001). However, unplanned (P < .001) admissions were higher in the rural group. There was no statistical difference in postoperative complications (P = .4). At 6 months, rural patients had higher patient-reported outcome measures (PROMs) including Hip Disability and Osteoarthritis Outcome Score total (P = .05), Hip Disability and Osteoarthritis Outcome Score interval (P = .05), self-reported functional improvement (P < .05), improvements in pain (P < .05), and that the surgery met expectations (P < .05). However, these values did not reach minimal clinically important difference.ConclusionsThere may be differences in emergency department visits, readmissions, and PROMs in rural vs urban populations undergoing total hip arthroplasty in an urban setting. Patient access to care and attitudes of rural patients toward health care may underlie these findings. Understanding differences in PROMs, satisfaction, and hospital-based outcomes based on rurality is essential to provide equitable arthroplasty care.

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Rethinking rurality: using hospital referral regions to investigate rural-urban health outcomes.

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Rethinking rurality: using hospital referral regions to investigate rural-urban health outcomes.

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