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OBJECTIVE: The aim of the study is to assess the necessity of chest X-ray (CXR) during the newborn hospitalization for all patients with prenatally suspected congenital pulmonary airway malformation (CPAM). STUDY DESIGN: This is a retrospective chart review of all infants delivered with prenatally suspected CPAM at our high-risk delivery hospital from January 2013 through April 2020 (n = 44). Nonparametric tests assessed the association between postnatal CXR findings, prescribed follow-up timeline, and neonatal outcomes. RESULTS: Mean follow-up period recommended was 6.4 weeks regardless of CXR findings in the neonatal period (p = 0.81). Additionally, patients who required respiratory support at or after birth were not more likely to have a lesion identified on chest X-ray (odds ratio [OR] = 0.72, 95% confidence interval [CI], 0.18-2.64, p = 0.71). CONCLUSION: Neonatal hospital course and future follow-up plan of patients with prenatally suspected CPAM were not altered by information from the CXR obtained in the immediate neonatal period, suggesting that this CXR may not be necessary in the asymptomatic patient. KEY POINTS: · Immediate postnatal X-ray of prenatally diagnosed CPAM does not alter planned follow-up interval.. · Immediate postnatal X-ray does not alter surgical plan for CPAM.. · Postnatal X-ray is not absolutely required for asymptomatic newborns with CPAM..
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Excess body weight is a risk factor for many chronic diseases. Studies have identified neighborhood greenery as supportive of healthy weight. However, few have considered plausible effect pathways for ecosystem services (e.g., heat mitigation, landscape aesthetics, and venues for physical activities) or potential variations by climate. This study examined associations between weight status and neighborhood greenery that capture ecosystem services most relevant to weight status across 28 U.S. communities. Weight status was defined by body mass index (BMI) reported for 6591 women from the U.S. Sister Study cohort. Measures of greenery within street and circular areas at 500 m and 2000 m buffer distances from homes were derived for each participant using 1 m land cover data. Street area was defined as a 25 m-wide zone on both sides of street centerlines multiplied by the buffer distances, and circular area was the area of the circle centered on a home within each of the buffer distances. Measures of street greenery characterized the pedestrian environment to capture physically and visually accessible greenery for shade and aesthetics. Circular greenery was generated for comparison. Greenery types of tree and herbaceous cover were quantified separately, and a combined measure of tree and herbaceous cover (i.e., aggregate greenery) was also included. Mixed models accounting for the clustering at the community level were applied to evaluate the associations between neighborhood greenery and the odds of being overweight or obese (BMI > 25) with adjustment for covariates selected using gradient boosted regression trees. Analyses were stratified by climate zone (arid, continental, and temperate). Tree cover was consistently associated with decreased odds of being overweight or obese. For example, the adjusted odds ratio [AOR] was 0.92, 95% Confidence Interval [CI]: 0.88-0.96, given a 10% increase in street tree cover at the 2000 m buffer across the 28 U.S. communities. These associations held across climate zones, with the lowest AOR in the arid climate (AOR: 0.74, 95% CI: 0.54-1.01). In contrast, associations with herbaceous cover varied by climate zone. For the arid climate, a 10% increase in street herbaceous cover at the 2000 m buffer was associated with lower odds of being overweight or obese (AOR: 0.75, 95% CI: 0.55-1.03), whereas the association was reversed for the temperate climate, the odds increased (AOR: 1.19, 95% CI: 1.05-1.35). Associations between greenery and overweight/obesity varied by type and spatial context of greenery, and climate. Our findings add to a growing body of evidence that greenery design in urban planning can support public health. These findings also justify further defining the mechanism that underlies the observed associations.
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Ecosistema , Características de la Residencia , Índice de Masa Corporal , Planificación de Ciudades , Ejercicio Físico , Femenino , Humanos , SobrepesoRESUMEN
BACKGROUND: The relationship between health and human interaction with nature is complex. Here we conduct analyses to provide insights into potential health benefits related to residential proximity to nature. OBJECTIVES: We aimed to examine associations between measures of residential nature and self-reported general health (SRGH), and to explore mediation roles of behavioral, social, and air quality factors, and variations in these relationships by urbanicity and regional climate. METHODS: Using residential addresses for 41,127 women from the Sister Study, a U.S.-based national cohort, we derived two nature exposure metrics, canopy and non-gray cover, using Percent Tree Canopy and Percent Developed Imperviousness from the National Land Cover Database. Residential circular buffers of 250 m and 1250 m were considered. Gradient boosted regression trees were used to model the effects of nature exposure on the odds of reporting better SRGH (Excellent/Very Good versus the referent, Good/Fair/Poor). Analyses stratified by urbanicity and regional climate (arid, continental, temperate) and mediation by physical activity, social support, and air quality were conducted. RESULTS: A 10% increase in canopy and non-gray cover within 1250 m buffer was associated with 1.02 (95% CI: 1.00-1.03) and 1.03 (95% CI: 1.01-1.04) times the odds of reporting better SRGH, respectively. Stronger associations were observed for the urban group and for continental climate relative to other strata. Social support and physical activity played a more significant mediation role than air quality for the full study population. DISCUSSION: Findings from this study identified a small but important beneficial association between residential nature and general health. These findings could inform community planning and investments in neighborhood nature for targeted health improvements and potential societal and environmental co-benefits.
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Contaminación del Aire , Salud Ambiental , Autoinforme , Estudios de Cohortes , Estudios Transversales , Ambiente , Femenino , HumanosRESUMEN
Analogous to the c-Myc (Myc)/Max family of bHLH-ZIP transcription factors, there exists a parallel regulatory network of structurally and functionally related proteins with Myc-like functions. Two related Myc-like paralogs, termed MondoA and MondoB/carbohydrate response element-binding protein (ChREBP), up-regulate gene expression in heterodimeric association with the bHLH-ZIP Max-like factor Mlx. Myc is necessary to support liver cancer growth, but not for normal hepatocyte proliferation. Here, we investigated ChREBP's role in these processes and its relationship to Myc. Unlike Myc loss, ChREBP loss conferred a proliferative disadvantage to normal murine hepatocytes, as did the combined loss of ChREBP and Myc. Moreover, hepatoblastomas (HBs) originating in myc-/-, chrebp-/-, or myc-/-/chrebp-/- backgrounds grew significantly more slowly. Metabolic studies on livers and HBs in all three genetic backgrounds revealed marked differences in oxidative phosphorylation, fatty acid ß-oxidation (FAO), and pyruvate dehydrogenase activity. RNA-Seq of livers and HBs suggested seven distinct mechanisms of Myc-ChREBP target gene regulation. Gene ontology analysis indicated that many transcripts deregulated in the chrebp-/- background encode enzymes functioning in glycolysis, the TCA cycle, and ß- and ω-FAO, whereas those dysregulated in the myc-/- background encode enzymes functioning in glycolysis, glutaminolysis, and sterol biosynthesis. In the myc-/-/chrebp-/- background, additional deregulated transcripts included those involved in peroxisomal ß- and α-FAO. Finally, we observed that Myc and ChREBP cooperatively up-regulated virtually all ribosomal protein genes. Our findings define the individual and cooperative proliferative, metabolic, and transcriptional roles for the "Extended Myc Network" under both normal and neoplastic conditions.
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Proliferación Celular/fisiología , Hepatoblastoma/patología , Hepatocitos/citología , Neoplasias Hepáticas Experimentales/patología , Proteínas Nucleares/fisiología , Proteínas Proto-Oncogénicas c-myc/fisiología , Factores de Transcripción/fisiología , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Ácidos Grasos/metabolismo , Perfilación de la Expresión Génica , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Hepatocitos/metabolismo , Metabolismo de los Lípidos , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Ratones , Ratones Noqueados , Proteínas Nucleares/genética , Fosforilación Oxidativa , Proteínas Proto-Oncogénicas c-myc/genética , Complejo Piruvato Deshidrogenasa/metabolismo , ARN Mensajero/genética , Proteínas Ribosómicas/genética , Factores de Transcripción/genética , Transcripción GenéticaRESUMEN
Obesity is a major international health concern. Neighborhood greenery has been identified as a critical factor for promoting health in urban areas, due in part to its apparent role in facilitating healthy weight by promoting physical activity. However, studies have used diverse greenery measures and spatial analysis units to ascertain this relationship. This study examined associations between street greenery and weight status at the residential address level across 500 to 2000m buffers in two climatically distinct communities, Phoenix, AZ, and Portland, OR. Greenery was measured using one-meter landcover data. Street greenery measures were designed to quantify the pedestrian environment along a gradient of suitability for promoting physical exercise. Weight status was defined by body mass index (BMI) calculated from weight and height information on driver's license records. BMI values were dichotomized at 25 into overweight or obese vs. neither. Approximately 500,000 BMI values in Phoenix and 225,000 in Portland were modelled by community using logistic regression. Street tree cover was consistently protective for healthy weight status across all buffer sizes after adjusting for potential confounders. Herbaceous street cover showed protective associations in Phoenix but harmful associations in Portland. Every 10% increase in street tree cover within 2000m was associated with 18% lower odds of being overweight or obese (adjusted odds ratio [AOR]: 0.82, 95% CI: 0.81 - 0.84 in Phoenix; 0.82, 95% CI: 0.81 - 0.83 in Portland). When compared to residents with less than 10% street tree cover within 2000m, those with greater than 10% tree cover had at least 13% (AOR for Portland: 0.87, 95% CI: 0.81 - 0.92) lower odds of being overweight or obese. Findings support the importance of urban street trees in very different climates for facilitating healthy weight status. They can inform greenery management to prioritize vegetation type and allocation decisions in limited urban spaces.
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BACKGROUND: Greater exposure to urban green spaces has been linked to reduced risks of depression, cardiovascular disease, diabetes and premature death. Alleviation of chronic stress is a hypothesized pathway to improved health. Previous studies linked chronic stress with a biomarker-based composite measure of physiological dysregulation known as allostatic load. OBJECTIVE: This study's objective was to assess the relationship between vegetated land cover near residences and allostatic load. METHODS: This cross-sectional population-based study involved 206 adult residents of the Durham-Chapel Hill, North Carolina metropolitan area. Exposure was quantified using high-resolution metrics of trees and herbaceous vegetation within 500m of each residence derived from the U.S. Environmental Protection Agency's EnviroAtlas land cover dataset. Eighteen biomarkers of immune, neuroendocrine, and metabolic functions were measured in serum or saliva samples. Allostatic load was defined as a sum of potentially unhealthy biomarker values dichotomized at 10th or 90th percentile of sample distribution. Regression analysis was conducted using generalized additive models with two-dimensional spline smoothing function of geographic coordinates, weighted measures of vegetated land cover allowing decay of effects with distance, and geographic and demographic covariates. RESULTS: An inter-quartile range increase in distance-weighted vegetated land cover was associated with 37% (95% Confidence Limits 46%; 27%) reduced allostatic load; significantly reduced adjusted odds of having low level of norepinephrine, dopamine, and dehydroepiandrosterone, and high level of epinephrine, fibrinogen, vascular cell adhesion molecule-1, and interleukin-8 in serum, and α-amylase in saliva; and reduced odds of previously diagnosed depression. CONCLUSIONS: The observed effects of vegetated land cover on allostatic load and individual biomarkers are consistent with prevention of depression, cardiovascular disease and premature mortality.
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Alostasis , Ambiente , Características de la Residencia , Adulto , Anciano , Anciano de 80 o más Años , Metabolismo Basal , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Humanos , Sistema Inmunológico , Masculino , Persona de Mediana Edad , Sistemas Neurosecretores , North Carolina , Adulto JovenRESUMEN
Following the discovery of the antidepressant properties of ketamine, there has been a recent resurgence in the interest in this NMDA receptor antagonist. Although detailed animal models of the molecular mechanisms underlying ketamine's effects have emerged, there are few MEG/EEG studies examining the acute subanesthetic effects of ketamine infusion in man. We recorded 275 channel MEG in two experiments (n = 25 human males) examining the effects of subanesthetic ketamine infusion. MEG power spectra revealed a rich set of significant oscillatory changes compared with placebo sessions, including decreases in occipital, parietal, and anterior cingulate alpha power, increases in medial frontal theta power, and increases in parietal and cingulate cortex high gamma power. Each of these spectral effects demonstrated their own set of temporal dynamics. Dynamic causal modeling of frontoparietal connectivity changes with ketamine indicated a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity. AMPA-mediated connectivity changes were sustained for up to 50 min after ketamine infusion had ceased, by which time perceptual distortions were absent. The results also indicated a decrease in gain of parietal pyramidal cells, which was correlated with participants' self-reports of blissful state. Based on these results, we suggest that the antidepressant effects of ketamine may depend on its ability to change the balance of frontoparietal connectivity patterns. SIGNIFICANCE STATEMENT: In this paper, we found that subanesthetic doses of ketamine, similar to those used in antidepressant studies, increase anterior theta and gamma power but decrease posterior theta, delta, and alpha power, as revealed by magnetoencephalographic recordings. Dynamic causal modeling of frontoparietal connectivity changes with ketamine indicated a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity. AMPA-mediated connectivity changes were sustained for up to 50 min after ketamine infusion had ceased, by which time perceptual distortions were absent. The results also indicated a decrease in gain of parietal pyramidal cells, which was correlated with participants' self-reports of blissful state. The alterations in frontoparietal connectivity patterns we observe here may be important in generating the antidepressant response to ketamine.
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Ondas Encefálicas/fisiología , Lóbulo Frontal/fisiología , Ketamina/administración & dosificación , Lóbulo Parietal/fisiología , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Adulto , Anestésicos Disociativos/administración & dosificación , Antidepresivos/administración & dosificación , Mapeo Encefálico , Ondas Encefálicas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Lóbulo Frontal/efectos de los fármacos , Humanos , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Lóbulo Parietal/efectos de los fármacos , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Adulto JovenRESUMEN
OBJECTIVE: Evaluate the impact of a multidisciplinary guideline standardizing antibiotic duration and enteral feeding practices following medical necrotizing enterocolitis (mNEC). STUDY DESIGN: For preterm infants with Bell Stage 2 A mNEC and negative blood culture, antibiotic treatment was standardized to 7 days. Trophic feeds of unfortified human milk began 72 h after resolution of pneumatosis. Feeds were advanced by 20 cc/kg/day starting on the last day of antibiotics. Primary outcomes were antibiotic days and days to full feeds, defined as 120 cc/kg/day of enteral nutrition. Secondary outcomes included central line days and length of stay (LOS). RESULTS: Antibiotic duration decreased 23%. Time to start trophic feeds and time to full feeds decreased 33 and 16% respectively. Central line use dropped (98 to 72% of infants) and central line days were reduced by 59%. CONCLUSION: Implementation of a mNEC QI package reduced antibiotic duration, time to full feeds, central line use and CL days.
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Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Recién Nacido , Humanos , Recien Nacido Prematuro , Enterocolitis Necrotizante/tratamiento farmacológico , Mejoramiento de la Calidad , Nutrición Enteral , Antibacterianos/uso terapéutico , Recién Nacido de muy Bajo PesoRESUMEN
We previously modeled Lyme disease (LD) risk at the landscape scale; here we evaluate the model's overall goodness-of-fit using holdout validation. Landscapes were characterized within road-bounded analysis units (AU). Observed LD cases (obsLD) were ascertained per AU. Data were randomly subset 2,000 times. Of 514 AU, 411 (80%) were selected as a training dataset to develop parameter estimates used to predict observations in the remaining 103 (20%) AU, the validation subset. Predicted values were subtracted from obsLD to quantify accuracy across iterations. We calculated the percentage difference of over- and under-estimation to assess bias. Predictive ability was strong and similar across iterations and datasets; the exact number of obsLD cases per AU were predicted almost 60% of the time. However, the three highest obsLD AU were under-predicted. Our model appears to be accurate and relatively unbiased, however is conservative at high disease incidence.
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Ambiente , Enfermedad de Lyme/epidemiología , Medición de Riesgo/métodos , Sesgo , Humanos , Incidencia , Enfermedad de Lyme/transmisión , Maryland/epidemiología , Modelos Biológicos , Características de la ResidenciaRESUMEN
BACKGROUND: Care for infants with Trisomy 13 and 18 is evolving with more children being offered medical and surgical interventions. Parents and clinicians of children diagnosed with trisomy 13 and 18 would benefit from understanding how parental goals of care correlate with the subsequent clinical course of children with these conditions. OBJECTIVE: To describe and compare parental goals of care (GOC) and clinical course in infants with trisomy 13 and 18. DESIGN: Single center, retrospective (2013-19) analysis of electronic health record repository at a birthing center and a tertiary care hospital. MEASUREMENTS: ICD-9/10 codes were used to identify patients with trisomy 13 or 18 born between 2013-2019. Their records were abstracted for their diagnosis, hospitalization days, interventions, GOC, death location and length of life. RESULT: Twenty-eight total patients were identified; trisomy 13, mosaic trisomy 13 and trisomy 18 were diagnosed in 9, 2 and 17 patients respectively. Among the 26 patients with complete trisomy 13 or 18, 8 had life-prolonging and 18 had comfort care goals at birth/diagnosis. Life-prolonging goals were not associated with longer life (p = 0.36) but were associated with more mean hospital days (70 vs. 12, p = 0.01), ICU days (66 vs. 9, p = 0.009), intubation (7/8 vs 7/18, p = 0.04), and death in ICU (7/7 vs. 10/17, p = 0.02). Zero patients underwent cardiac surgery. CONCLUSION: Parental GOC did not affect length of life in children with complete trisomy, but did alter treatment intensity. This may inform decision making for patients with trisomy 13 or 18.
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Cuidados Paliativos , Comodidad del Paciente , Niño , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Trisomía , Síndrome de la Trisomía 13/terapia , Síndrome de la Trisomía 18RESUMEN
RATIONALE: The role of NADPH oxidase activation in pneumonia is complex because reactive oxygen species contribute to both microbial killing and regulation of the acute pulmonary infiltrate. The relative importance of each role remains poorly defined in community-acquired pneumonia. OBJECTIVES: We evaluated the contribution of NADPH oxidase-derived reactive oxygen species to the pathogenesis of pneumococcal pneumonia, addressing both the contribution to microbial killing and regulation of the inflammatory response. METHODS: Mice deficient in the gp91(phox) component of the phagocyte NADPH oxidase were studied after pneumococcal challenge. MEASUREMENTS AND MAIN RESULTS: gp91(phox)(-/-) mice demonstrated no defect in microbial clearance as compared with wild-type C57BL/6 mice. A significant increase in bacterial clearance from the lungs of gp91(phox)(-/-) mice was associated with increased numbers of neutrophils in the lung, lower rates of neutrophil apoptosis, and enhanced activation. Marked alterations in pulmonary cytokine/chemokine expression were also noted in the lungs of gp91(phox)(-/-) mice, characterized by elevated levels of tumor necrosis factor-alpha, KC, macrophage inflammatory protein-2, monocyte chemotactic protein-1, and IL-6. The greater numbers of neutrophils in gp91(phox)(-/-) mice were not associated with increased lung injury. Levels of neutrophil elastase in bronchoalveolar lavage were not decreased in gp91(phox)(-/-) mice. CONCLUSIONS: During pneumococcal pneumonia, NADPH oxidase-derived reactive oxygen species are redundant for host defense but limit neutrophil recruitment and survival. Decreased NADPH oxidase-dependent reactive oxygen species production is well tolerated and improves disease outcome during pneumococcal pneumonia by removing neutrophils from the tight constraints of reactive oxygen species-mediated regulation.
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Glicoproteínas de Membrana/deficiencia , NADPH Oxidasas/inmunología , Neutrófilos/inmunología , Neumonía Neumocócica/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Inflamación , Glicoproteínas de Membrana/inmunología , Ratones , Ratones Noqueados , NADPH Oxidasa 2 , NADPH Oxidasas/deficiencia , Infiltración Neutrófila , Neutrófilos/microbiología , Neumonía Neumocócica/fisiopatología , Especies Reactivas de Oxígeno/inmunologíaRESUMEN
MN58b is a novel anticancer drug that inhibits choline kinase, resulting in inhibition of phosphocholine synthesis. The aim of this work was to develop a noninvasive and robust pharmacodynamic biomarker for target inhibition and, potentially, tumor response following MN58b treatment. Human HT29 (colon) and MDA-MB-231 (breast) carcinoma cells were examined by proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) before and after treatment with MN58b both in culture and in xenografts. An in vitro time course study of MN58b treatment was also carried out in MDA-MB-231 cells. In addition, enzymatic assays of choline kinase activity in cells were done. A decrease in phosphocholine and total choline levels (P < 0.05) was observed in vitro in both cell lines after MN58b treatment, whereas the inactive analogue ACG20b had no effect. In MDA-MB-231 cells, phosphocholine fell significantly as early as 4 hours following MN58b treatment, whereas a drop in cell number was observed at 48 hours. Significant correlation was also found between phosphocholine levels (measured by MRS) and choline kinase activities (r2 = 0.95, P = 0.0008) following MN58b treatment. Phosphomonoesters also decreased significantly (P < 0.05) in both HT29 and MDA-MB-231 xenografts with no significant changes in controls. 31P-MRS and 1H-MRS of tumor extracts showed a significant decrease in phosphocholine (P < or = 0.05). Inhibition of choline kinase by MN58b resulted in altered phospholipid metabolism both in cultured tumor cells and in vivo. Phosphocholine levels were found to correlate with choline kinase activities. The decrease in phosphocholine, total choline, and phosphomonoesters may have potential as noninvasive pharmacodynamic biomarkers for determining tumor response following treatment with choline kinase inhibitors.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Butanos/farmacología , Carcinoma/tratamiento farmacológico , Colina Quinasa/antagonistas & inhibidores , Neoplasias del Colon/tratamiento farmacológico , Compuestos de Piridinio/farmacología , Animales , Antineoplásicos/farmacología , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/metabolismo , Carcinoma/enzimología , Neoplasias del Colon/enzimología , Neoplasias del Colon/metabolismo , Inhibidores Enzimáticos/farmacología , Células HT29 , Humanos , Ratones , Ratones Desnudos , Resonancia Magnética Nuclear Biomolecular/métodos , Fósforo , Fosforilcolina/metabolismo , Protones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because greenspace can promote physical activity, reduce stress and buffer air pollutants, it may have beneficial effects for people at risk of SUD, such as those with heart disease, hypertension, and diabetes mellitus. Using several spatial techniques, this study explored the relationship between SUD and greenspace. We adjudicated 396 SUD cases that occurred from March 2013 to February 2015 among reports from emergency medical services (EMS) that attended out-of-hospital deaths in Wake County (central North Carolina, USA). We measured multiple greenspace metrics in each census tract, including the percentages of forest, grassland, average tree canopy, tree canopy diversity, near-road tree canopy and greenway density. The associations between SUD incidence and these greenspace metrics were examined using Poisson regression (non-spatial) and Bayesian spatial models. The results from both models indicated that SUD incidence was inversely associated with both greenway density (adjusted risk ratio [RR]â¯=â¯0.82, 95% credible/ confidence interval [CI]: 0.69-0.97) and the percentage of forest (adjusted RRâ¯=â¯0.90, 95% CI: 0.81-0.99). These results suggest that increases in greenway density by 1â¯km/km2 and in forest by 10% were associated with a decrease in SUD risk of 18% and 10%, respectively. The inverse relationship was not observed between SUD incidence and other metrics, including grassland, average tree canopy, near-road tree canopy and tree canopy diversity. This study implies that greenspace, specifically greenways and forest, may have beneficial effects for people at risk of SUD. Further studies are needed to investigate potential causal relationships between greenspace and SUD, and potential mechanisms such as promoting physical activity and reducing stress.
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Muerte Súbita Cardíaca/epidemiología , Bosques , Análisis Espacial , Ejercicio Físico/fisiología , Humanos , Modelos Estadísticos , North Carolina/epidemiologíaRESUMEN
SUMMARY: From climate change to hydraulic fracturing, and from drinking water safety to wildfires, environmental challenges are changing. The United States has made substantial environmental protection progress based on media-specific and single pollutant risk-based frameworks. However, today's environmental problems are increasingly complex and new scientific approaches and tools are needed to achieve sustainable solutions to protect the environment and public health. In this article, we present examples of today's environmental challenges and offer an integrated systems approach to address them. We provide a strategic framework and recommendations for advancing the application of science for protecting the environment and public health. We posit that addressing 21st century challenges requires transdisciplinary and systems approaches, new data sources, and stakeholder partnerships. To address these challenges, we outline a process driven by problem formulation with the following steps: a) formulate the problem holistically, b) gather and synthesize diverse information, c) develop and assess options, and d) implement sustainable solutions. This process will require new skills and education in systems science, with an emphasis on science translation. A systems-based approach can transcend media- and receptor-specific bounds, integrate diverse information, and recognize the inextricable link between ecology and human health.
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Conservación de los Recursos Naturales/métodos , Contaminación Ambiental/estadística & datos numéricos , Cambio Climático , Monitoreo del Ambiente , Contaminación Ambiental/prevención & controlRESUMEN
Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR.
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Proliferación Celular , Ciclo del Ácido Cítrico , Glucólisis , Hepatocitos/metabolismo , Proteínas Mitocondriales/metabolismo , Acetilcoenzima A/metabolismo , Animales , Células Cultivadas , Femenino , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Hepatoblastoma/patología , Hepatocitos/citología , Immunoblotting , Ratones Noqueados , Proteínas Mitocondriales/genética , Fosforilación Oxidativa , Complejo Piruvato Deshidrogenasa/genética , Complejo Piruvato Deshidrogenasa/metabolismo , Ácido Pirúvico/metabolismo , Análisis de Supervivencia , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Incidence of Lyme disease in the US continues to grow. Low-density development is also increasing in endemic regions, raising questions about the relationship between development pattern and disease. This study sought to model Lyme disease incidence rate using quantitative, practical metrics of regional landscape pattern. The objective was to progress towards the development of design guidelines that may help minimize known threats to human and environmental health. METHODS: Ecological analysis was used to accommodate the integral landscape variables under study. Case data derived from passive surveillance reports across 12 counties in the US state of Maryland during 1996-2000; 2,137 cases were spatially referenced to residential addresses. Major roads were used to delineate 514 landscape analysis units from 0.002 to 580 km(2). RESULTS: The parameter that explained the most variation in incidence rate was the percentage of land-cover edge represented by the adjacency of forest and herbaceous cover [R(2) = 0.75; rate ratio = 1.34 (1.26-1.43); P < 0.0001]. Also highly significant was the percentage of the landscape in forest cover (cumulative R(2) = 0.82), which exhibited a quadratic relationship with incidence rate. Modelled relationships applied throughout the range of landscape sizes. CONCLUSIONS: Results begin to provide quantitative landscape design parameters for reducing casual peridomestic contact with tick and host habitat. The final model suggests that clustered forest and herbaceous cover, as opposed to high forest-herbaceous interspersion, would minimize Lyme disease risk in low-density residential areas. Higher-density development that precludes a large percentage of forest-herbaceous edge would also limit exposure.
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Planificación Ambiental , Enfermedad de Lyme/epidemiología , Enfermedad de Lyme/prevención & control , Ecosistema , Agricultura Forestal/métodos , Agricultura Forestal/estadística & datos numéricos , Guías como Asunto , Humanos , Incidencia , Renta/estadística & datos numéricos , Enfermedad de Lyme/transmisión , Maryland/epidemiología , Características de la Residencia/estadística & datos numéricos , ÁrbolesAsunto(s)
COVID-19 , Enfermedades Fetales , Neonatología/tendencias , Atención Perinatal , Complicaciones del Embarazo , Telemedicina , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/epidemiología , Accesibilidad a los Servicios de Salud , Humanos , Control de Infecciones/métodos , Atención Perinatal/organización & administración , Atención Perinatal/tendencias , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/prevención & control , Relaciones Profesional-Familia , Evaluación de Programas y Proyectos de Salud , Consulta Remota/organización & administración , Consulta Remota/estadística & datos numéricos , SARS-CoV-2 , Telemedicina/métodos , Telemedicina/organización & administración , Estados Unidos/epidemiologíaRESUMEN
This study assessed how landcover classification affects associations between landscape characteristics and Lyme disease rate. Landscape variables were derived from the National Land Cover Database (NLCD), including native classes (e.g., deciduous forest, developed low intensity) and aggregate classes (e.g., forest, developed). Percent of each landcover type, median income, and centroid coordinates were calculated by census tract. Regression results from individual and aggregate variable models were compared with the dispersion parameter-based R(2) (Rα(2)) and AIC. The maximum Rα(2) was 0.82 and 0.83 for the best aggregate and individual model, respectively. The AICs for the best models differed by less than 0.5%. The aggregate model variables included forest, developed, agriculture, agriculture-squared, y-coordinate, y-coordinate-squared, income and income-squared. The individual model variables included deciduous forest, deciduous forest-squared, developed low intensity, pasture, y-coordinate, y-coordinate-squared, income, and income-squared. Results indicate that regional landscape models for Lyme disease rate are robust to NLCD landcover classification resolution.