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1.
Philos Trans A Math Phys Eng Sci ; 381(2262): 20220183, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37866383

RESUMO

The overturning circulation of the subpolar North Atlantic (SPNA) plays a fundamental role in Earth's climate variability and change. Here, we show from observations that the recent warming period since about 2016 in the eastern SPNA involves increased western boundary density at the intergyre boundary, likely due to enhanced buoyancy forcing as a response to the strong increase in the North Atlantic Oscillation since the early 2010s. As these deep positive density anomalies spread southward along the western boundary, they enhance the North Atlantic Current and associated meridional heat transport at the intergyre region, leading to increased influx of subtropical heat into the eastern SPNA. Based on the timing of this chain of events, we conclude that this recent warming phase since about 2016 is primarily associated with this observed mechanism of changes in deep western boundary density, an essential element in these interactions. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

2.
Philos Trans A Math Phys Eng Sci ; 381(2262): 20220187, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37866390

RESUMO

The latest assessment report from the Intergovernmental Panel on Climate Change concluded that the Atlantic Meridional Overturning Circulation (AMOC) was very likely to decline over the twenty-first century under all emissions scenarios; however, there was low confidence in the magnitude of the decline. Recent research has highlighted that model biases in the mean climate state can affect the AMOC in its mean state, variability and its response to climate change. Hence, understanding and reducing these model biases is critical for reducing uncertainty in the future changes of the AMOC and in its impacts on the wider climate. We discuss how model biases, in particular salinity biases, influence the AMOC and deep convection. We then focus on biases in the UK HadGEM3-GC3-1 climate model and how these biases change with resolution. We also discuss ongoing model development activities that affect these biases, and highlight priorities for improved representation of processes, such as the position of the North Atlantic Current, transports in narrow boundary current, resolution (or improved parameterization) of eddies and spurious numerical mixing in overflows. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

3.
PLoS Pathog ; 16(12): e1008686, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370399

RESUMO

Helicobacter pylori chronically infects the stomach of approximately half of the world's population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 1,767 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A maximum likelihood tree based on genetic similarity clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple niches within the stomach during chronic infection.


Assuntos
Úlcera Duodenal/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Gastropatias/microbiologia , Animais , Atrofia/microbiologia , Doença Crônica , Ácido Gástrico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Gastropatias/patologia
4.
Am J Perinatol ; 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-35858648

RESUMO

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..

5.
J Clin Nurs ; 31(9-10): e11-e13, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34888970

RESUMO

In the past few years, there has been a very significant rise in the number of children and young people seeking treatment for gender dysphoria This area is the subject of much discussion, as evidenced in a recent court case in the UK which examined competence and capacity of young people to consent to potentially irreversible interventions. Clinicians involved in gaining consent to puberty blockers for gender dysphoric young people, must understand the evidence in this area and be aware of the heavy burden of accountability placed upon them.


Assuntos
Disforia de Gênero , Adolescente , Conscientização , Criança , Disforia de Gênero/tratamento farmacológico , Identidade de Gênero , Humanos , Puberdade , Responsabilidade Social
6.
Environ Res ; 199: 111327, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34019899

RESUMO

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.


Assuntos
Ecossistema , Características de Residência , Índice de Massa Corporal , Planejamento de Cidades , Exercício Físico , Feminino , Humanos , Sobrepeso
7.
Environ Res ; 183: 109176, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32311902

RESUMO

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.


Assuntos
Poluição do Ar , Saúde Ambiental , Autorrelato , Estudos de Coortes , Estudos Transversais , Meio Ambiente , Feminino , Humanos
8.
Remote Sens Environ ; 244: 1-111796, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32665744

RESUMO

Decision-making that impacts sustainability occurs at national and subnational levels, highlighting the need for multi-scale Earth observations (EO) and geospatial data for assessing the United Nations' Sustainable Development Goals (SDGs). EnviroAtlas, developed by the United States Environmental Protection Agency and partners, provides a collection of web-based, interactive maps of environmental and socio-economic data relevant to the SDGs. EnviroAtlas maps ecosystem services indicators at national, regional, and local extents that can contribute to targets set forth in numerous goals, such as SDG 6 for clean water, SDG 11 for sustainable cities and communities, and SDG 15 for life on land. Examples of EnviroAtlas indicators that provide a way to view spatial inequalities, help fill gaps in environmental indicators, and integrate socio-economic and environmental data for the SDGs are explored herein. Remotely sensed EO data are essential for producing these indicators and informing planning and decision-making for the SDGs at subnational scales. The National Land Cover Dataset is the basis for many EnviroAtlas maps at the national extent, while National Agriculture Imagery Program and Light Detection and Ranging (LiDAR) data are used to classify Meter-scale Urban Land Cover in select US metro areas. These 30 meter and 1 meter land cover products are combined with demographic and other geospatial data (remotely sensed and otherwise) to produce integrated indicators that can aid in target setting of the SDGs. Though EnviroAtlas was created for the conterminous US, the methods for indicator creation are transferable, and the open-source code for the EnviroAtlas resource may serve as an example for other nations. Achieving the SDGs means assessing targets and decision-making outcomes at local, regional, and national levels using consistent and accurate data. Geospatial resources like EnviroAtlas that provide open access to indicators based on EO data and allow for assessment at multiple extents and resolutions are critical to broadly addressing national to subnational SDG goals and targets.

9.
J Biol Chem ; 293(38): 14740-14757, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30087120

RESUMO

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.


Assuntos
Proliferação de Células/fisiologia , Hepatoblastoma/patologia , Hepatócitos/citologia , Neoplasias Hepáticas Experimentais/patologia , Proteínas Nucleares/fisiologia , Proteínas Proto-Oncogênicas c-myc/fisiologia , Fatores de Transcrição/fisiologia , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Ácidos Graxos/metabolismo , Perfilação da Expressão Gênica , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética , Fosforilação Oxidativa , Proteínas Proto-Oncogênicas c-myc/genética , Complexo Piruvato Desidrogenase/metabolismo , RNA Mensageiro/genética , Proteínas Ribossômicas/genética , Fatores de Transcrição/genética , Transcrição Gênica
10.
Syst Biol ; 67(4): 559-575, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325126

RESUMO

Data synthesis required for large-scale macroevolutionary studies is challenging with the current tools available for integration. Using a classic question regarding the frequency of paired fin loss in teleost fishes as a case study, we sought to create automated methods to facilitate the integration of broad-scale trait data with a sizable species-level phylogeny. Similar to the evolutionary pattern previously described for limbs, pelvic and pectoral fin reduction and loss are thought to have occurred independently multiple times in the evolution of fishes. We developed a bioinformatics pipeline to identify the presence and absence of pectoral and pelvic fins of 12,582 species. To do this, we integrated a synthetic morphological supermatrix of phenotypic data for the pectoral and pelvic fins for teleost fishes from the Phenoscape Knowledgebase (two presence/absence characters for 3047 taxa) with a species-level tree for teleost fishes from the Open Tree of Life project (38,419 species). The integration method detailed herein harnessed a new combined approach by utilizing data based on ontological inference, as well as phylogenetic propagation, to reduce overall data loss. Using inference enabled by ontology-based annotations, missing data were reduced from 98.0% to 85.9%, and further reduced to 34.8% by phylogenetic data propagation. These methods allowed us to extend the data to an additional 11,293 species for a total of 12,582 species with trait data. The pectoral fin appears to have been independently lost in a minimum of 19 lineages and the pelvic fin in 48. Though interpretation is limited by lack of phylogenetic resolution at the species level, it appears that following loss, both pectoral and pelvic fins were regained several (3) to many (14) times respectively. Focused investigation into putative regains of the pectoral fin, all within one clade (Anguilliformes), showed that the pectoral fin was regained at least twice following loss. Overall, this study points to specific teleost clades where strategic phylogenetic resolution and genetic investigation will be necessary to understand the pattern and frequency of pectoral fin reversals.


Assuntos
Nadadeiras de Animais/anatomia & histologia , Evolução Biológica , Biologia Computacional/métodos , Peixes/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Padronização Corporal , Peixes/crescimento & desenvolvimento , Filogenia
11.
Urban For Urban Green ; 41: 104-107, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31031577

RESUMO

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.

12.
Br J Nurs ; 28(11): 682-689, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31188655

RESUMO

Oral colonisation by pathogens contributes to contracting ventilator-associated pneumonia (VAP). The aim of this review was to determine whether the use of the antiseptic chlorhexidine in the intra-oral cavity reduced its incidence in the critically ill, mechanically ventilated adult. The findings from this review led to the conclusion that chlorhexidine reduced the occurrence of VAP. Although a recommendation to implement the use of intra-oral chlorhexidine for mechanically-ventilated patients within critical care can be made, further exploration into required frequency and method of administration would be beneficial to reduce unnecessary exposure and hinder pathogenic resistance.


Assuntos
Clorexidina/uso terapêutico , Higiene Bucal/métodos , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Respiração Artificial/efeitos adversos , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
J Biol Chem ; 292(24): 10068-10086, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28432125

RESUMO

Hepatocellular carcinoma (HCC) is a common cancer that frequently overexpresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical, and molecular changes accompanying HCC progression, regression, and recurrence. These involved altered rates of pyruvate and fatty acid ß-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain complexes I and II to respiration. The uncoupling of complex II's electron transport function from its succinate dehydrogenase activity also suggested a mechanism by which Myc generates reactive oxygen species. RNA sequence studies revealed an orderly progression of transcriptional changes involving pathways pertinent to DNA damage repair, cell cycle progression, insulin-like growth factor signaling, innate immunity, and further metabolic re-programming. Only a subset of functions deregulated in initial tumors was similarly deregulated in recurrent tumors thereby indicating that the latter can "normalize" some behaviors to suit their needs. An interactive and freely available software tool was developed to allow continued analyses of these and other transcriptional profiles. Collectively, these studies define the metabolic, biochemical, and molecular events accompanyingHCCevolution, regression, and recurrence in the absence of any potentially confounding therapies.


Assuntos
Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Regulação para Cima , Animais , Carcinogênese , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/prevenção & controle , Reparo do DNA , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/metabolismo , Feminino , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Fígado/patologia , Masculino , Camundongos Transgênicos , Renovação Mitocondrial , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Proteínas Proto-Oncogênicas c-myc/genética , Espécies Reativas de Oxigênio/metabolismo , Carga Tumoral
14.
PLoS Biol ; 13(1): e1002033, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25562316

RESUMO

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.


Assuntos
Estudos de Associação Genética , Animais , Biologia Computacional , Curadoria de Dados , Bases de Dados Factuais/normas , Interação Gene-Ambiente , Genômica , Humanos , Fenótipo , Padrões de Referência , Reprodutibilidade dos Testes , Terminologia como Assunto
15.
Pediatr Nephrol ; 33(4): 553-571, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28286898

RESUMO

Over recent years routine ultrasound scanning has identified increasing numbers of neonates as having hydronephrosis and pelvi-ureteric junction obstruction (PUJO). This patient group presents a diagnostic and management challenge for paediatric nephrologists and urologists. In this review we consider the known molecular mechanisms underpinning PUJO and review the potential of utilising this information to develop novel therapeutics and diagnostic biomarkers to improve the care of children with this disorder.


Assuntos
Biomarcadores/metabolismo , Hidronefrose/congênito , Rim Displásico Multicístico/metabolismo , Obstrução Ureteral/metabolismo , Animais , Predisposição Genética para Doença , Humanos , Hidronefrose/genética , Hidronefrose/metabolismo , Hidronefrose/terapia , Pelve Renal/patologia , Biologia Molecular , Terapia de Alvo Molecular/métodos , Rim Displásico Multicístico/genética , Rim Displásico Multicístico/terapia , Mutação , Ureter/patologia , Obstrução Ureteral/genética , Obstrução Ureteral/terapia
16.
J Biol Chem ; 291(51): 26241-26251, 2016 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-27738108

RESUMO

Hepatoblastoma (HB) is associated with aberrant activation of the ß-catenin and Hippo/YAP signaling pathways. Overexpression of mutant ß-catenin and YAP in mice induces HBs that express high levels of c-Myc (Myc). In light of recent observations that Myc is unnecessary for long-term hepatocyte proliferation, we have now examined its role in HB pathogenesis using the above model. Although Myc was found to be dispensable for in vivo HB initiation, it was necessary to sustain rapid tumor growth. Gene expression profiling identified key molecular differences between myc+/+ (WT) and myc-/- (KO) hepatocytes and HBs that explain these behaviors. In HBs, these included both Myc-dependent and Myc-independent increases in families of transcripts encoding ribosomal proteins, non-structural factors affecting ribosome assembly and function, and enzymes catalyzing glycolysis and lipid bio-synthesis. In contrast, transcripts encoding enzymes involved in fatty acid ß-oxidation were mostly down-regulated. Myc-independent metabolic changes associated with HBs included dramatic reductions in mitochondrial mass and oxidative function, increases in ATP content and pyruvate dehydrogenase activity, and marked inhibition of fatty acid ß-oxidation (FAO). Myc-dependent metabolic changes included higher levels of neutral lipid and acetyl-CoA in WT tumors. The latter correlated with higher histone H3 acetylation. Collectively, our results indicate that the role of Myc in HB pathogenesis is to impose mutually dependent changes in gene expression and metabolic reprogramming that are unattainable in non-transformed cells and that cooperate to maximize tumor growth.


Assuntos
Regulação Neoplásica da Expressão Gênica , Hepatoblastoma/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Acetilcoenzima A/genética , Acetilcoenzima A/metabolismo , Trifosfato de Adenosina/genética , Trifosfato de Adenosina/metabolismo , Animais , Metabolismo Energético/genética , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Perfilação da Expressão Gênica , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-myc/genética
17.
Environ Res ; 158: 508-521, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28709033

RESUMO

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.


Assuntos
Alostase , Meio Ambiente , Características de Residência , Adulto , Idoso , Idoso de 80 Anos ou mais , Metabolismo Basal , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Sistema Imunitário , Masculino , Pessoa de Meia-Idade , Sistemas Neurossecretores , North Carolina , Adulto Jovem
18.
Rev Panam Salud Publica ; 41: e127, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31384260

RESUMO

The year 2017 marks the 40th year of the establishment of the Expanded Program on Immunization (EPI) by the Pan American Health Organization (PAHO), the regional office of the World Health Organization (WHO) in the Americas, the first WHO region certified as eliminating poliomyelitis (1994), measles (2016), and rubella and congenital rubella syndrome (CRS) (2015). The English- and Dutch-speaking Caribbean subregion of the Americas paved the way in eliminating these diseases. This report highlights the innovative strategies used in this subregion that helped make the EPI a success. A review of published/unpublished reports and written and oral accounts of the experiences of Immunization Advisors and national EPI managers was conducted to identify the strategies used to strengthen the Immunization program in the subregion since its implementation by countries in 1977. The results show that these include strong collective political commitment, country-specific immunization legislation, joint use of a standard coverage monitoring chart, annual meetings of national EPI managers, collaborative development of annual national Plans of Action for Immunization, coordinated implementation of vaccination campaigns, subregional oversight of surveillance and laboratory support, a performance award system for countries, and subregional standardized templates for immunization manuals and procedural guidelines. Political will and support for immunization has been particularly strong in this subregion, where 99% of EPI costs are borne by governments. Dedicated health staff and multi-country agreement and application of strategies have led to high sustained coverage and good-quality surveillance, resulting in the absence of wild polio for 34 years, measles for 25 years, CRS for 17 years, and rubella for 15 years.


En el 2017 se celebra el cuadragésimo año de la instauración del Programa Ampliado de Inmunización (PAI) por la Organización Panamericana de la Salud (OPS), la Oficina Regional de la Organización Mundial de la Salud (OMS) para las Américas. Esta fue la primera región de la OMS que obtuvo la certificación de la eliminación de la poliomielitis (1994), el sarampión (2016) y la rubéola y el síndrome de rubéola congénita (2015). La subregión de habla inglesa y holandesa del Caribe en las Américas abrió el camino a la eliminación de estas enfermedades. En el presente artículo se destacan las estrategias innovadoras utilizadas en esta subregión que contribuyeron al éxito del PAI.Se llevó a cabo una revisión de los informes publicados e inéditos y de los relatos escritos y orales de las experiencias de los Expertos en Inmunización y los gerentes nacionales del PAI con el objeto de determinar las estrategias utilizadas con miras a fortalecer el programa de vacunación en la subregión, desde su introducción en los países en 1977. Los resultados ponen de manifiesto que los programas comportaban un fuerte compromiso político colectivo, legislaciones en materia de inmunización propias de cada país, la utilización común de un registro gráfico normalizado de monitoreo de coberturas de vacunación, reuniones anuales de los gerentes nacionales del PAI, la elaboración conjunta de planes de acción anuales nacionales sobre vacunas, la ejecución coordinada de campañas de vacunación, la supervisión de la vigilancia y el apoyo a los laboratorios a escala subregional, un sistema de reconocimiento al desempeño de los países y plantillas subregionales normalizadas de los manuales de vacunación y los procedimientos recomendados. La voluntad política y el apoyo a la vacunación han sido muy sólidos en esta subregión, donde los gobiernos sufragan 99% de los costos del PAI. La existencia de personal sanitario dedicado y los acuerdos multinacionales y la aplicación de las estrategias permitieron alcanzar una alta cobertura de manera sostenida y una vigilancia de buena calidad, cuyo resultado fue la ausencia de poliomielitis salvaje durante 34 años, de sarampión durante 25 años, del síndrome de la rubéola congénita durante 17 años y de la rubéola durante 15 años.


O ano de 2017 marca o 40º aniversário da criação do Programa Ampliado de Imunização (PAI) pela Organização Pan-Americana da Saúde (OPAS), Escritório Regional da Organização Mundial da Saúde (OMS) nas Américas, primeira Região da OMS certificada como tendo eliminado a poliomielite (1994), o sarampo (2016) e a rubéola e síndrome da rubéola congênita (2015). A sub-região das Américas constituída pelos países do Caribe de língua inglesa e holandesa abriu caminho ao eliminar essas doenças. Este relato destaca as estratégias inovadoras usadas nesta sub-região que contribuíram para tornar o PAI um programa bem-sucedido.Foi realizada uma análise de informes publicados/inéditos e relatos orais e escritos da experiência dos assessores para assuntos de imunização e coordenadores nacionais do PAI visando identificar as estratégias aplicadas para consolidar o programa nos países da sub-região desde a sua implementação em 1977. Os resultados demonstram firme compromisso político coletivo, legislação de vacinação própria em cada país, uso conjunto de uma lista padrão para o monitoramento da cobertura, reuniões anuais dos coordenadores nacionais do PAI, desenvolvimento colaborativo de planos de ação nacionais anuais para vacinação, campanhas coordenadas de vacinação, supervisão sub-regional da vigilância e infraestrutura laboratorial, sistema de premiação dos países por bom desempenho, modelos padronizados para os manuais de vacinação e protocolos de procedimentos. A sub-região se caracteriza sobretudo pela vontade e apoio políticos para vacinação, sendo 99% do custo do PAI financiados pelos governos. Equipes de saúde diligentes, acordos entre vários países e emprego de estratégias são fatores que contribuem para elevada cobertura sustentada e vigilância de boa qualidade com a consequente não ocorrência de casos de poliomielite por vírus selvagem por 34 anos, de casos de sarampo por 25 anos, de casos de síndrome da rubéola congênita por 17 anos e de casos de rubéola por 15 anos.

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