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1.
Artigo em Inglês | MEDLINE | ID: mdl-39038705

RESUMO

Over the past two decades, epidemiologic studies have identified significant associations between exposure to violence, as a psychosocial stressor, and the incidence or exacerbation of asthma. Across diverse populations, study designs, and measures of community violence, researchers have consistently identified adverse associations. In this review, the published epidemiologic evidence is summarized, with special attention to research published in the last five years and seminal papers. Hypothesized mechanisms for direct effects of violence exposure, and for how such exposure affects susceptibility to physical agents (e.g., air pollution, extreme temperature) are discussed. These include stress-related pathways, behavioral mechanisms, and epigenetic mechanisms. Finally, clinical implications and recommendations are discussed.

2.
Vet Ophthalmol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468143

RESUMO

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

3.
J Allergy Clin Immunol ; 152(2): 378-385.e2, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36990323

RESUMO

BACKGROUND: Research suggests demographic, economic, residential, and health-related factors influence vulnerability to environmental exposures. Greater environmental vulnerability may exacerbate environmentally related health outcomes. We developed a neighborhood environmental vulnerability index (NEVI) to operationalize environmental vulnerability on a neighborhood level. OBJECTIVE: We explored the relationship between NEVI and pediatric asthma emergency department (ED) visits (2014-19) in 3 US metropolitan areas: Los Angeles County, Calif; Fulton County, Ga; and New York City, NY. METHODS: We performed separate linear regression analyses examining the association between overall NEVI score and domain-specific NEVI scores (demographic, economic, residential, health status) with pediatric asthma ED visits (per 10,000) across each area. RESULTS: Linear regression analyses suggest that higher overall and domain-specific NEVI scores were associated with higher annual pediatric asthma ED visits. Adjusted R2 values suggest that overall NEVI scores explained at least 40% of the variance in pediatric asthma ED visits. Overall NEVI scores explained more of the variance in pediatric asthma ED visits in Fulton County. NEVI scores for the demographic, economic, and health status domains explained more of the variance in pediatric asthma ED visits in each area compared to the NEVI score for the residential domain. CONCLUSION: Greater neighborhood environmental vulnerability was associated with greater pediatric asthma ED visits in each area. The relationship differed in effect size and variance explained across the areas. Future studies can use NEVI to identify populations in need of greater resources to mitigate the severity of environmentally related outcomes, such as pediatric asthma.


Assuntos
Asma , Nevo , Criança , Humanos , Asma/epidemiologia , Morbidade , Serviço Hospitalar de Emergência , Características de Residência
4.
J Urban Health ; 100(5): 1007-1023, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37594675

RESUMO

Compared to previous studies commonly using a single summary score, we aimed to construct a multidomain neighborhood environmental vulnerability index (NEVI) to characterize the magnitude and variability of area-level factors with the potential to modify the association between environmental pollutants and health effects. Using the Toxicological Prioritization Index framework and data from the 2015-2019 U.S. Census American Community Survey and the 2020 CDC PLACES Project, we quantified census tract-level vulnerability overall and in 4 primary domains (demographic, economic, residential, and health status), 24 subdomains, and 54 distinct area-level features for New York City (NYC). Overall and domain-specific indices were calculated by summing standardized feature values within the subdomains and then aggregating and weighting based on the number of features within each subdomain within equally-weighted primary domains. In citywide comparisons, NEVI was correlated with multiple existing indices, including the Neighborhood Deprivation Index (r = 0.91) and Social Vulnerability Index (r = 0.87) but provided additional information on features contributing to vulnerability. Vulnerability varied spatially across NYC, and hierarchical cluster analysis using subdomain scores revealed six patterns of vulnerability across domains: 1) low in all, 2) primarily low except residential, 3) medium in all, 4) high demographic, economic, and residential 5) high economic, residential, and health status, and 6) high demographic, economic and health status. Created using methods that offer flexibility for theory-based construction, NEVI provided detailed vulnerability metrics across domains that can inform targeted research and public health interventions aimed at reducing the health impacts from environmental exposures across urban centers.


Assuntos
Exposição Ambiental , Nevo , Humanos , Cidade de Nova Iorque , Nível de Saúde , Saúde Pública
5.
Environ Res ; 231(Pt 3): 116235, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37244495

RESUMO

Ambient air pollution, temperature, and social stressor exposures are linked with asthma risk, with potential synergistic effects. We examined associations for acute pollution and temperature exposures, with modification by neighborhood violent crime and socioeconomic deprivation, on asthma morbidity among children aged 5-17 years year-round in New York City. Using conditional logistic regression in a time-stratified, case-crossover design, we quantified percent excess risk of asthma event per 10-unit increase in daily, residence-specific exposures to PM2.5, NO2, SO2, O3, and minimum daily temperature (Tmin). Data on 145,834 asthma cases presenting to NYC emergency departments from 2005 to 2011 were obtained from the New York Statewide Planning and Research Cooperative System (SPARCS). Residence- and day-specific spatiotemporal exposures were assigned using the NYC Community Air Survey (NYCCAS) spatial data and daily EPA pollution and NOAA weather data. Point-level NYPD violent crime data for 2009 (study midpoint) was aggregated, and Socioeconomic Deprivation Index (SDI) scores assigned, by census tract. Separate models were fit for each pollutant or temperature exposure for lag days 0-6, controlling for co-exposures and humidity, and mutually-adjusted interactions (modification) by quintile of violent crime and SDI were assessed. We observed stronger main effects for PM2.5 and SO2 in the cold season on lag day 1 [4.90% (95% CI: 3.77-6.04) and 8.57% (5.99-11.21), respectively]; Tmin in the cold season on lag day 0 [2.26% (1.25-3.28)]; and NO2 and O3 in the warm season on lag days 1 [7.86% (6.66-9.07)] and 2 [4.75% (3.53-5.97)], respectively. Violence and SDI modified the main effects in a non-linear manner; contrary to hypotheses, we found stronger associations in lower-violence and -deprivation quintiles. At very high stressor exposures, although asthma exacerbations were highly prevalent, pollution effects were less apparent-suggesting potential saturation effects in socio-environmental synergism.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Criança , Humanos , Poluentes Atmosféricos/análise , Asma/epidemiologia , Asma/etiologia , Exposição Ambiental/análise , Cidade de Nova Iorque/epidemiologia , Dióxido de Nitrogênio/análise , Material Particulado/análise , Fatores Socioeconômicos , Temperatura , Violência , Estudos Cross-Over
6.
Yale J Biol Med ; 96(2): 171-184, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37396984

RESUMO

Despite increasing awareness of the public and global health ramifications of climate change, there is a lack of curricula discussing climate change within medical education. Where greater societal awareness and improved scientific understanding have begun to grab the attention of members of the medical education community, there is the precedent, the desire, and the need to incorporate climate-health topics into medical education. We hosted semi-structured interviews (n=9) with faculty members at different institutions across the country who have been involved with climate change education. We pursued a qualitative approach to begin an inter-institutional conversation and better understand what support our colleagues and peers need to expand climate-health education, and we identified a set of key barriers to implementation: Obtaining Institutional Resources, Formalizing Initiative Leadership, and Empowering Faculty Involvement. We also began to appreciate the creative strategies that programs across the country have employed to tackle these challenges. Working with interested students to manage workload, advocating for funded faculty positions, and integrating curricular materials in multiple formats are just a few of the approaches that have helped climate-health initiatives to achieve longevity and penetration in the curriculum. A better identification of the challenges and drivers for success in curricular efforts can provide a roadmap to more efficient implementation of climate-health topics within medical education.


Assuntos
Mudança Climática , Educação Médica , Humanos , Currículo , Educação em Saúde , Docentes
7.
Paediatr Perinat Epidemiol ; 36(1): 36-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34164839

RESUMO

BACKGROUND: Emerging literature has documented heat-related impacts on child health, yet few studies have evaluated the effects of heat among children of different age groups and comparing emergency department (ED) and hospitalisation risks. OBJECTIVES: To examine the differing associations between high ambient temperatures and risk of ED visits and hospitalisations among children by age group in New York City (NYC). METHODS: We used New York Statewide Planning and Research Cooperative System (SPARCS) data on children aged 0-18 years admitted to NYC EDs (n = 2,252,550) and hospitals (n = 228,006) during the warm months (May-September) between 2005 and 2011. Using a time-stratified, case-crossover design, we estimated the risk of ED visits and hospitalisations associated with daily maximum temperature (Tmax) for children of all ages and by age group. RESULTS: The average Tmax over the study period was 80.3°F (range 50°, 104°F). Tmax conferred the greatest risk of ED visits for children aged 0-4, with a 6-day cumulative excess risk of 2.4% (95% confidence interval [CI] 1.7, 3.0) per 13°F (ie interquartile range) increase in temperature. Children and adolescents 5-12 years (0.8%, 95% CI 0.1, 1.6) and 13-18 years (1.4%, 95% CI 0.6, 2.3) are also sensitive to heat. For hospitalisations, only adolescents 13-18 years had increased heat-related risk, with a cumulative excess risk of 7.9% (95% CI 2.0, 14.2) per 13°F increase in Tmax over 85°F. CONCLUSIONS: This urban study in NYC reinforces that young children are particularly vulnerable to effects of heat, but also demonstrates the sensitivity of older children and adolescents as well. These findings underscore the importance of focussing on children and adolescents in targeting heat illness prevention and emergency response activities, especially as global temperatures continue to rise.


Assuntos
Serviço Hospitalar de Emergência , Temperatura Alta , Adolescente , Criança , Pré-Escolar , Hospitais , Humanos , Cidade de Nova Iorque/epidemiologia , Temperatura
8.
Int J Biometeorol ; 66(8): 1575-1588, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35622168

RESUMO

Individuals in the USA are insufficiently active, increasing their chronic disease risk. Extreme temperatures may reduce physical activity due to thermal discomfort. Cooler climate studies have suggested climate change may have a net positive effect on physical activity, yet research gaps remain for warmer climates and within-day physical activity patterns. We determined the association between ambient temperatures (contemporary and projected) and urban trail use in a humid subtropical climate. At a trail in Austin, TX, five electronic counters recorded hourly pedestrian and cyclist counts in 2019. Weather data were acquired from World Weather Online. Generalized additive models estimated the association between temperature and trail counts. We then combined the estimated exposure-response relation with weather projections from climate models for intermediate (RCP4.5) and high (RCP8.5) emissions scenarios by NASA NEX-GDDP. From summer to autumn to spring to winter, hourly trail counts shifted from bimodal (mid-morning and early-evening peaks) to one mid-day peak. Pedestrians were more likely to use the trail between 7 and 27 °C (45-81°F) with peak use at 17 °C (63°F) and cyclists between 15 and 33 °C (59-91°F) with peak use at 27 °C (81°F) than at temperature extremes. A net decrease in trail use was estimated by 2041-2060 (RCP4.5: pedestrians = - 4.5%, cyclists = - 1.1%; RCP8.5: pedestrians = - 6.6%, cyclists = - 1.6%) and 2081-2100 (RCP4.5: pedestrians = - 7.5%, cyclists = - 1.9%; RCP8.5: pedestrians = - 16%, cyclists = - 4.5%). Results suggest climate change may reduce trail use. We recommend interventions for thermal comfort at settings for physical activity.


Assuntos
Mudança Climática , Pedestres , Exercício Físico , Humanos , Temperatura , Texas
9.
Int J Biometeorol ; 66(8): 1683-1698, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35751701

RESUMO

Global climate change is leading to higher ambient temperatures and more frequent heatwaves. To date, impacts of ambient extreme heat on childhood morbidity have been understudied, although-given children's physiologic susceptibility, with smaller body surface-to-mass ratios, and many years of increasing temperatures ahead-there is an urgent need for better information to inform public health policies and clinical approaches. In this review, we aim to (1) identify pediatric morbidity outcomes previously associated with extreme heat, (2) to identify predisposing co-morbidities which may make children more susceptible to heat-related outcomes, and (3) to map the current body of available literature. A scoping review of the current full-text literature was conducted using the Arksey and O'Malley framework Int J Soc Res Methodol 8:19-32, (2015). Search terms for (1) pediatric population, (2) heat exposures, (3) ambient conditions, and (4) adverse outcomes were combined into a comprehensive PubMed and Medline literature search. Of the 1753 publications identified, a total of 20 relevant studies were ultimately selected based on selection criteria of relevance to US urban populations. Most identified studies supported positive associations between high extreme temperature exposures and heat-related illness, dehydration/electrolyte imbalance, general symptoms, diarrhea and digestion disorders, infectious diseases/infections, asthma/wheeze, and injury. Most studies found no association with renal disease, cardiovascular diseases, or diabetes mellitus. Results were mixed for other respiratory diseases and mental health/psychological disorders. Very few of the identified studies examined susceptibility to pre-existing conditions; Cystic Fibrosis was the only co-morbidity for which we found significant evidence. Further research is needed to understand the nuances of associations between extreme heat and specific outcomes-particularly how associations may vary by child age, sex, race/ ethnicity, community characteristics, and other pre-existing conditions.


Assuntos
Calor Extremo , Transtornos de Estresse por Calor , Criança , Mudança Climática , Calor Extremo/efeitos adversos , Transtornos de Estresse por Calor/epidemiologia , Temperatura Alta , Humanos , Morbidade
10.
J Urban Health ; 98(6): 700-710, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34845655

RESUMO

Childhood asthma exacerbation remains the leading cause of pediatric emergency department visits and hospitalizations and disproportionately affects Latinx and Black children, compared to non-Latinx White children in NYC. Environmental exposures and socioeconomic factors may jointly contribute to childhood asthma exacerbations; however, they are often studied separately. To better investigate the multiple contributors to disparities in childhood asthma, we compiled data on various individual and neighborhood level socioeconomic and environmental factors, including education, race/ethnicity, income disparities, gentrification, housing characteristics, built environment, and structural racism, from the NYC Department of Health's KIDS 2017 survey and the US Census' American Community Survey. We applied cluster analysis and logistic regression to first identify the predominant patterns of social and environmental factors experienced by children in NYC and then estimate whether children experiencing specific patterns are more likely to experience asthma exacerbations. We found that housing and built environment characteristics, such as density and age of buildings, were the predominant features to differentiate the socio-environmental patterns observed in New York City. Children living in neighborhoods with greater proportions of rental housing, high-density buildings, and older buildings were more likely to experience asthma exacerbations than other children. These findings add to the literature about childhood asthma in urban environments, and can assist efforts to target actionable policies and practices that promote health equity related to childhood asthma.


Assuntos
Asma , Racismo Sistêmico , Asma/epidemiologia , Criança , Análise por Conglomerados , Promoção da Saúde , Humanos , Cidade de Nova Iorque/epidemiologia , Características de Residência
11.
Am J Emerg Med ; 45: 297-302, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33046311

RESUMO

INTRODUCTION: Mortality for out-of-hospital cardiac arrest is high when traditional chest compressions are used without adjuncts. The abdominal aortic and junctional tourniquet (AAJT) is a device with a wedge-shaped air bladder that occludes the aortic bifurcation, augmenting blood flow to the heart and brain. Previously, the addition of AAJT during chest compression led to an increase in rate of survival in a model of traumatic cardiac arrest. HYPOTHESIS: This study was designed to determine if application of the AAJT would lead to more effective chest compressions as measured by improved hemodynamic parameters and an increased rate of return of spontaneous circulation (ROSC). METHODS: Yorkshire swine (n = 6 per group) underwent general anesthesia and instrumentation. Ventricular fibrillation (Vfib) was electrically induced and animals were allocated into groups with or without the AAJT. The AAJT was inflated if selected after four minutes of compressions. Following a total of ten minutes of compressions, the animals entered into a ten-minute advanced cardiac life support phase. Hemodynamics and blood gas measurements were compared between groups. RESULTS: ROSC or cardioversion from Vfib was not achieved in either group. The AAJT group had improved hemodynamic parameters with significantly higher carotid diastolic pressure and higher blood flow in the carotid artery (p = 0.016 and 0.028 respectively). However, no significant differences were observed with coronary perfusion pressure or end tidal CO2. CONCLUSION: The AAJT did not confer a survival advantage during chest compressions, but hemodynamic improvements were observed while the AAJT was in place.


Assuntos
Aorta Abdominal , Reanimação Cardiopulmonar , Torniquetes , Fibrilação Ventricular , Animais , Reanimação Cardiopulmonar/métodos , Modelos Animais de Doenças , Monitorização Hemodinâmica , Estudos Prospectivos , Suínos , Fibrilação Ventricular/terapia
12.
Cereb Cortex ; 29(8): 3655-3665, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-30272146

RESUMO

22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition associated with a high prevalence of neuropsychiatric conditions that include autism spectrum disorder (ASD). While evidence suggests that clinical phenotypes represent distinct neurodevelopmental outcomes, it remains unknown whether this translates to the level of neurobiology. To fractionate the 22q11.2DS phenotype on the level of neuroanatomy, we examined differences in vertex-wise estimates of cortical volume, surface area, and cortical thickness between 1) individuals with 22q11.2DS (n = 62) and neurotypical controls (n = 57) and 2) 22q11.2DS individuals with ASD symptomatology (n = 30) and those without (n = 25). We firstly observed significant differences in surface anatomy between 22q11.2DS individuals and controls for all 3 neuroanatomical features, predominantly in parietotemporal regions, cingulate and dorsolateral prefrontal cortices. We also established that 22q11.2DS individuals with ASD symptomatology were neuroanatomically distinct from 22q11.2DS individuals without ASD symptoms, particularly in brain regions that have previously been linked to ASD (e.g., dorsolateral prefrontal cortices and the entorhinal cortex). Our findings indicate that different clinical 22q11.2DS phenotypes, including those with ASD symptomatology, may represent different neurobiological subgroups. The spatially distributed patterns of neuroanatomical differences associated with ASD symptomatology in 22q11.2DS may thus provide useful information for patient stratification and the prediction of clinical outcomes.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Síndrome de DiGeorge/diagnóstico por imagem , Adolescente , Adulto , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/psicologia , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/patologia , Síndrome de DiGeorge/psicologia , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Humanos , Masculino , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adulto Jovem
13.
Med Teach ; 42(10): 1097-1101, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32734808

RESUMO

A number of planetary boundaries, including climate change as a result of greenhouse gas emissions, has already been exceeded. This situation has deleterious consequences for public health. Paradoxically, 4.4% of these emissions are attributable to the healthcare sector. These problems have not been sufficiently acknowledged in health professions curricula. This paper addresses two main issues, humanistic learning and the application of knowledge acquisition to clinical practice. Humanistic learning principles can be used to emphasize learner-centered approaches, including knowledge acquisition and reflection to increase self-awareness. Applying humanistic principles in everyday life and clinical practice can encourage stewardship, assisting students to become agents for change. In terms of knowledge and skills application to clinical practice, an overview of varied and novel approaches of how sustainable education can be integrated at different stages of training across several health care professions is provided. The Health and Environment Adaptive Response Taskforce (HEART) platform as an example of creating empowered learners, the NurSusTOOLKIT, a multi-disciplinary collaboration offering free adaptable educational resources for educators and the Greener Anaesthesia and Sustainability Project (GASP), an example of bridging the transition to clinical practice, are described.


Assuntos
Currículo , Aprendizagem , Atenção à Saúde , Ocupações em Saúde , Humanos , Prática Profissional
14.
Circulation ; 138(3): 305-315, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30012703

RESUMO

Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver. The National Heart, Lung, and Blood Institute convened a working group to discuss how LDs affect cardiovascular diseases. The goal of the working group was to examine the current state of knowledge on the cell biology of LDs, including current methods to study them in cells and organs and reflect on how LDs influence the development and progression of cardiovascular diseases. This review summarizes the working group discussion and recommendations on research areas ripe for future investigation that will likely improve our understanding of atherosclerosis and heart function.


Assuntos
Doenças Cardiovasculares/metabolismo , Gotículas Lipídicas/metabolismo , Miocárdio/metabolismo , Animais , Doenças Cardiovasculares/genética , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Modelos Animais de Doenças , Interação Gene-Ambiente , Humanos , Metabolismo dos Lipídeos , National Heart, Lung, and Blood Institute (U.S.) , Estados Unidos
15.
Gen Comp Endocrinol ; 282: 113215, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276671

RESUMO

RT-PCR analysis of gar pituitary and brain indicated that different combinations of gar melanocortin receptor mRNAs are present in the same tissues with mRNAs for gar mrap1 and gar mrap2. Against this background, an objective of this study was to determine whether the ligand sensitivity for either ACTH or α-MSH was affected when gar (g) melanocortin receptors (Mcrs) were co-expressed with either of the accessory proteins gMrap1 or gMrap2 in Chinese Hamster Ovary cells. The results indicated that gMc2r has an obligatory requirement for co-expression with gMrap1 in order for the receptor to be activated by hACTH(1-24). In addition, activation of gMc2r did not occur when the receptor was expressed alone or co-expressed with gMrap2. Furthermore, co-expression of gMc2r with gMrap1 followed by stimulation with NDP-MSH resulted in a low level of activation (only at 10-7 M and 10-6 M). However, gMc1r, gMc3r, gMc4r, and gMc5r responded to stimulation by NDP-MSH in a more robust manner. Co-expression of gMc1r, gMc3r, gMc4r, and gMc5r with gMRAP1 had no effect on sensitivity to stimulation by NDP-MSH or hACTH(1-24). Co-expression with gMRAP2 had no negative or positive effect on ligand sensitivity for gMc1r, gMc3r, and gMc5r, however this treatment did increase the activation of CHO cells transfected with gMc4r following stimulation with both hACTH(1-24) (p < 0.001), and NDP-MSH (p < 0.001). Co-expression of gMC5R with either gMRAP1 or gMRAP2 increased trafficking of gMC5R to the plasma membrane. These pharmacological observations are compared to the response of melanocortin receptors from other neopterygian fishes, cartilaginous fishes, and tetrapods to stimulation by ACTH(1-24) and forms of α-MSH.


Assuntos
Peixes/metabolismo , Receptores de Melanocortina/metabolismo , Transdução de Sinais , Hormônio Adrenocorticotrópico/farmacologia , Sequência de Aminoácidos , Animais , Células CHO , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Peixes/genética , Regulação da Expressão Gênica , Genes Reporter , Humanos , Ligantes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Melanocortina/química , Receptores de Melanocortina/genética
16.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454910

RESUMO

The interaction between the pituitary hormone, adrenocorticotropin (ACTH), and melanocortin-2 receptor (MC2R) orthologs involves the H6 F7 R8 W9 and R/K15 K16 R17 R18 motifs in ACTH making contact with corresponding contact sites on MC2R. Earlier studies have localized the common HFRW binding site of all melanocortin receptors to residues in TM2, TM3, and TM6 that are located close to the extracellular space. The current study has identified residues in Xenopus tropicalis (xt) MC2R in TM4 (I158, F161), in EC2 (M166), and in TM5 (V172) that also are involved in activation of xtMC2R, and may be in the R/KKRR contact site of xtMC2R. These results are compared to earlier studies on the corresponding domains of human MC2R and rainbow trout MC2R in an effort to identify common features in the activation of teleost and tetrapod MC2R orthologs following stimulation with ACTH.


Assuntos
Receptor Tipo 2 de Melanocortina/metabolismo , Xenopus/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Sequência de Aminoácidos , Animais , Células CHO , Membrana Celular/metabolismo , Cricetulus , Humanos , Mutação , Receptor Tipo 2 de Melanocortina/agonistas , Receptor Tipo 2 de Melanocortina/química , Receptor Tipo 2 de Melanocortina/genética , Xenopus/genética
17.
Osteoarthritis Cartilage ; 26(12): 1658-1665, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30144513

RESUMO

OBJECTIVE: To evaluate systemic inflammatory biomarkers in symptomatic knee osteoarthritis (OA) and their association with radiographic and biochemical OA progression. METHODS: Lipopolysaccharide (LPS) binding protein (LBP), soluble Toll-like receptor 4 (sTLR4) and interleukin 6 (IL-6) were measured in plasma of 431 knee OA patients from the doxycycline (DOXY) trial at baseline and 18 months. Plasma lipopolysaccharide and lipopolysaccharide binding protein (LBP) were also measured at 12 months. As a biochemical indicator of disease activity and OA progression, urinary (u) C-telopeptide of Type II collagen (uCTX-II) was measured in samples collected at baseline and 18 months. Change over 16 months in radiographic tibiofemoral joint space width (JSW in mm) and joint space narrowing (JSN≥0.5 mm) were used to indicate radiographic OA progression. Change over 18 months for uCTX-II was used as a secondary outcome. Both univariate and multivariable regression analyses were performed to test the association between Z-score transformed biomarkers and outcomes. RESULTS: Baseline LBP and time-integrated concentration (TIC) of LBP over 12 and 18 months were associated with worsening joint space width (JSW) (parameter estimates: -0.1 to -0.07) and JSN (OR: 1.32 to 1.42) adjusting for treatment group, age, body mass index (BMI) and corresponding baseline radiographic measures. Baseline sTLR4 and TIC over 18 months were associated with change in uCTX-II over 18 months (adjusted parameter estimates: 0.0017 to 0.0020). Results were not modified by treatment with doxycycline. CONCLUSION: Plasma LBP and sTLR4 were associated with knee OA progression over 16-18 months. These results lend further support for a role of systemic low-grade inflammation in the pathogenesis of knee OA progression.


Assuntos
Proteínas de Transporte/sangue , Mediadores da Inflamação/sangue , Glicoproteínas de Membrana/sangue , Osteoartrite do Joelho/diagnóstico , Receptor 4 Toll-Like/sangue , Proteínas de Fase Aguda , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Progressão da Doença , Método Duplo-Cego , Doxiciclina/uso terapêutico , Feminino , Seguimentos , Humanos , Articulação do Joelho/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/tratamento farmacológico , Prognóstico , Radiografia , Índice de Gravidade de Doença
18.
Public Health ; 161: 119-126, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29960726

RESUMO

OBJECTIVES: High ambient temperatures are associated with significant health risk in the United States. The risk to children has been minimally explored, and often young children are considered as a single age group despite marked physiologic and social variation among this population from infancy through preschool. This study explored the heterogeneity of risk of heat among young children. STUDY DESIGN: Using a time-stratified, case-crossover design, we evaluated associations between maximum daily temperature (Tmax) and ED visits (n = 1,002,951) to New York City (NYC) metropolitan area hospitals for children aged 0-4 years in May-September, 2005-2011. METHODS: Conditional logistic regression analysis estimated risks for an interquartile range of Tmax for 0-6 lag days. Stratified analyses explored age strata by year, race/ethnic groups, and diagnostic codes. Sensitivity analyses controlled for same day ambient ozone, particulate matter <2.5 microns, and relative humidity and, separately, explored race groups without ethnicity and different diagnostic code groupings. RESULTS: Children ages 0-4 years had increased risk of emergency department visits with increased Tmax on lag days 0, 1, and 3. The association was strongest on lag day 0, when an increase in Tmax of 13 °F conferred an excess risk of 2.6% (95% confidence interval [CI]: 2.2-3.0). Stratifying by age, we observed significant positive associations for same-day exposures, for 1-4 year olds. Children less than 1 year of age showed a significant positive association with Tmax only on lag day 3. The race/ethnicity stratified analysis revealed a similar lag pattern for all subgroups. The diagnostic group analysis showed percent excess risk for heat-specific diagnoses (16.6% [95% CI: 3.0-31.9]); general symptoms (10.1% [95% CI: 8.2-11.9]); infectious (4.9% [95% CI: 3.9-5.9]); and injury (5.1% [95% CI: 3.8-6.4]) diagnoses. CONCLUSION: We found a significant risk of ED visits in young children with elevated Tmax. Risk patterns vary based on age with infants showing delayed risk and toddlers and preschoolers with same day risk. In addition, the finding of increased risk of injury associated with higher temperatures is novel. Altogether, these findings suggest a need for a tailored public health response, such as different messages to caregivers of different age children, to protect children from the effects of heat. Next steps include examining specific subcategories of diagnoses to develop protective strategies and better anticipate the needs of population health in future scenarios of climate change.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Temperatura Alta/efeitos adversos , Distribuição por Idade , Pré-Escolar , Estudos Cross-Over , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Cidade de Nova Iorque , Risco
19.
Arch Womens Ment Health ; 20(6): 803-810, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28770342

RESUMO

The ten-item Edinburgh Postnatal Depression Scale (EPDS) is one of the most widely used self-report measures of postpartum depression. Although originally described as a one-dimensional measure, the recognition that depressive symptoms may be differentially experienced across cultural and racial/ethnic groups has led to studies examining structural equivalence of the EPDS in different populations. Variation of the factor structure remains understudied across racial/ethnic groups of US women. We examined the factor structure of the EPDS assessed 6 months postpartum in 515 women (29% black, 53% Hispanic, 18% white) enrolled in an urban Boston longitudinal birth cohort. Exploratory factor analysis (EFA) identified that a three-factor model, including depression, anxiety, and anhedonia subscales, was the most optimal fit in our sample as a whole and across race/ethnicity. Confirmatory factor analysis (CFA) was used to examine the fit of both the two- and three-factor models reported in prior research. CFA confirmed the best fit for a three-factor model, with minimal differences across race/ethnicity. "Things get on top of me" loaded on the anxiety factor among Hispanics, but loaded on the depression factor in whites and African Americans. These findings suggest that EPDS factor structure may need to be adjusted for diverse samples and warrants further study.


Assuntos
Ansiedade/diagnóstico , Depressão Pós-Parto/diagnóstico , Depressão/diagnóstico , Etnicidade/psicologia , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Adulto , Anedonia , Ansiedade/psicologia , Depressão/etnologia , Depressão/psicologia , Depressão Pós-Parto/etnologia , Depressão Pós-Parto/psicologia , Etnicidade/estatística & dados numéricos , Análise Fatorial , Feminino , Humanos , Período Pós-Parto/psicologia , Pobreza , Psicometria/instrumentação , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Autorrelato , Classe Social , Estados Unidos
20.
Foot Ankle Surg ; 22(4): 265-269, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27810026

RESUMO

BACKGROUND: Debate exists regarding the effect of triple fusion on the development of osteoarthritis (OA) of the ankle joint. The midterm outcome after triple arthrodesis and the prevalence of OA following triple arthrodesis are reported in this study. The role of alignment in the development of OA was investigated. METHODS: Seventy five patients (87 feet) were evaluated in 2003 and of these, 48 patients (55 feet) were available for second evaluation in 2008. X-rays of the ankles and feet were made prior to surgery, in 2003 and in 2008, and the level of osteoarthritis (OA) was graded with the Kellgren and Lawrence score. Of all postoperative X-rays, the AP and lateral talo first metatarsal angle X-rays were compared. Also, standardized digital photos were made to assess the geometry/alignment. The Foot Function Index (FFI) and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score were completed. In order to investigate the role of the underlying alignment on the aggravation of ankle osteoarthritis, patients were divided into a 'varus' and a 'valgus' group based on the indication for surgery. RESULTS: The outcome scores (AOFAS and FFI) after triple arthrodesis remained stable in the present 7.5-year follow-up study. An important increase of OA of the ankle was not established, 58% of the patients showed no aggravation, 31% one-grade and 2% two-grade increase of OA. A trend was found (P=.063) towards aggravation of OA of the ankle in patients of the varus group with the highest medial arches (persistent cavovarus deformity). CONCLUSION: This study reports minor, not statistically significant, changes of the ankle joint following triple arthrodesis after 7.5 years. Clinical outcome remained stable in time. Clinical relevance It seems that triple arthrodesis as such does not lead to major osteoarthritis of the ankle, given that adequate alignment of the hindfoot is achieved. LEVEL OF EVIDENCE: Level II, retrospective study.


Assuntos
Articulação do Tornozelo/cirurgia , Artrodese/métodos , Progressão da Doença , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Adulto , Idoso , Articulação do Tornozelo/fisiopatologia , Artrodese/efeitos adversos , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
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