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1.
Nat Mater ; 19(1): 43-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31740791

RESUMO

The family of layered thio- and seleno-phosphates has gained attention as potential control dielectrics for the rapidly growing family of two-dimensional and quasi-two-dimensional electronic materials. Here we report a combination of density functional theory calculations, quantum molecular dynamics simulations and variable-temperature, -pressure and -bias piezoresponse force microscopy data to predict and verify the existence of an unusual ferroelectric property-a uniaxial quadruple potential well for Cu displacements-enabled by the van der Waals gap in copper indium thiophosphate (CuInP2S6). The calculated potential energy landscape for Cu displacements is strongly influenced by strain, accounting for the origin of the negative piezoelectric coefficient and rendering CuInP2S6 a rare example of a uniaxial multi-well ferroelectric. Experimental data verify the coexistence of four polarization states and explore the temperature-, pressure- and bias-dependent piezoelectric and ferroelectric properties, which are supported by bias-dependent molecular dynamics simulations. These phenomena offer new opportunities for both fundamental studies and applications in data storage and electronics.

2.
Am J Hum Genet ; 98(4): 653-66, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27018471

RESUMO

Linear mixed models (LMMs) are widely used in genome-wide association studies (GWASs) to account for population structure and relatedness, for both continuous and binary traits. Motivated by the failure of LMMs to control type I errors in a GWAS of asthma, a binary trait, we show that LMMs are generally inappropriate for analyzing binary traits when population stratification leads to violation of the LMM's constant-residual variance assumption. To overcome this problem, we develop a computationally efficient logistic mixed model approach for genome-wide analysis of binary traits, the generalized linear mixed model association test (GMMAT). This approach fits a logistic mixed model once per GWAS and performs score tests under the null hypothesis of no association between a binary trait and individual genetic variants. We show in simulation studies and real data analysis that GMMAT effectively controls for population structure and relatedness when analyzing binary traits in a wide variety of study designs.


Assuntos
Estudos de Associação Genética/métodos , Genética Populacional/métodos , Modelos Lineares , Fenótipo , Asma/genética , Estudos de Casos e Controles , América Central , Simulação por Computador , Técnicas de Genotipagem , Humanos , Modelos Logísticos , Modelos Genéticos , Filogeografia , Polimorfismo de Nucleotídeo Único , América do Sul
3.
Nano Lett ; 18(3): 2016-2020, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29388778

RESUMO

Two-dimensional (2D) materials have generated interest in the scientific community because of the advanced electronic applications they might offer. Powerful electron beam microscopes have been used not only to evaluate the structures of these materials but also to manipulate them by forming vacancies, nanofragments, and nanowires or joining nanoislands together. In this work, we show that the electron beam in a scanning transmission electron microscope (STEM) can be used in yet another way: to mediate the synthesis of 2D 1 H-MoSe2 from Mo-decorated 2D ß-FeSe and simultaneously image the process on the atomic scale. This is quite remarkable given the different crystal structures of the reactant (square lattice ß-FeSe) and the product (hexagonal lattice 1 H-MoSe2). The feasibility of the transformation was first explored by theoretical calculations that predicted that the reaction is exothermic. Furthermore, a theoretical reaction path to forming a stable 1 H-MoSe2 nucleation kernel within pure ß-FeSe was found, demonstrating that the pertinent energy barriers are smaller than the energy supplied by the STEM electron beam.

4.
J Allergy Clin Immunol ; 140(4): 996-1003.e7, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28167095

RESUMO

BACKGROUND: Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. OBJECTIVE: We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. METHODS: A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. RESULTS: Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10-8), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10-9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1/forced vital capacity replicated in the independent cohorts. CONCLUSIONS: Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.


Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Interação Gene-Ambiente , Pulmão/fisiologia , Polimorfismo de Nucleotídeo Único , Adolescente , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Interleucina-17/metabolismo , Masculino , Ligação Proteica , Porto Rico , Testes de Função Respiratória
5.
Am J Respir Cell Mol Biol ; 57(4): 439-447, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28574721

RESUMO

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.


Assuntos
Asma , Regulação da Expressão Gênica , Genômica , Subunidade alfa de Receptor de Interleucina-5 , Modelos Biológicos , Polimorfismo Genético , Adolescente , Asma/genética , Asma/metabolismo , Asma/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Interleucina-5/biossíntese , Subunidade alfa de Receptor de Interleucina-5/genética , Masculino , Porto Rico/epidemiologia
6.
Eur Respir J ; 49(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28461288

RESUMO

Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans.The only locus to achieve genome-wide significance was chromosome 17q21, as evidenced by our top single nucleotide polymorphism (SNP), rs907092 (OR 0.71, p=1.2×10-12) at IKZF3 Similar to results in non-Puerto Ricans, SNPs in genes in the same linkage disequilibrium block as IKZF3 (e.g. ZPBP2, ORMDL3 and GSDMB) were significantly associated with asthma in Puerto Ricans. With regard to results from a meta-analysis in Europeans, we replicated findings for rs2305480 at GSDMB, but not for SNPs in any other genes. On the other hand, we replicated results from a meta-analysis of North American populations for SNPs at IL1RL1, TSLP and GSDMB but not for IL33Our findings suggest that common variants on chromosome 17q21 have the greatest effects on asthma in Puerto Ricans.


Assuntos
Asma/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Asma/etnologia , Criança , Cromossomos Humanos Par 17/genética , Feminino , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Adulto Jovem
7.
Am J Respir Crit Care Med ; 192(1): 47-56, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25918834

RESUMO

RATIONALE: Stress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR). OBJECTIVES: To examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma. METHODS: This was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids. MEASUREMENTS AND MAIN RESULTS: High child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the ß2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety). CONCLUSIONS: High child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.


Assuntos
Ansiedade/complicações , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Estresse Psicológico/complicações , Adolescente , Ansiedade/diagnóstico , Ansiedade/etnologia , Ansiedade/genética , Asma/complicações , Asma/etnologia , Asma/genética , Estudos de Casos e Controles , Criança , Estudos Transversais , Regulação para Baixo , Feminino , Marcadores Genéticos , Genótipo , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Porto Rico , Receptores Adrenérgicos beta 2/genética , Rhode Island , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/etnologia , Resultado do Tratamento
8.
J Allergy Clin Immunol ; 136(4): 885-92.e2, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25913104

RESUMO

BACKGROUND: Gene-environment interaction studies using genome-wide association study data are often underpowered after adjustment for multiple comparisons. Differential gene expression in response to the exposure of interest can capture the most biologically relevant genes at the genome-wide level. OBJECTIVE: We used differential genome-wide expression profiles from the Epidemiology of Home Allergens and Asthma birth cohort in response to Der f 1 allergen (sensitized vs nonsensitized) to inform a gene-environment study of dust mite exposure and asthma severity. METHODS: Polymorphisms in differentially expressed genes were identified in genome-wide association study data from the Childhood Asthma Management Program, a clinical trial in childhood asthmatic patients. Home dust mite allergen levels (<10 or ≥10 µg/g dust) were assessed at baseline, and (≥1) severe asthma exacerbation (emergency department visit or hospitalization for asthma in the first trial year) served as the disease severity outcome. The Genetics of Asthma in Costa Rica Study and a Puerto Rico/Connecticut asthma cohort were used for replication. RESULTS: IL9, IL5, and proteoglycan 2 expression (PRG2) was upregulated in Der f 1-stimulated PBMCs from dust mite-sensitized patients (adjusted P < .04). IL9 polymorphisms (rs11741137, rs2069885, and rs1859430) showed evidence for interaction with dust mite in the Childhood Asthma Management Program (P = .02 to .03), with replication in the Genetics of Asthma in Costa Rica Study (P = .04). Subjects with the dominant genotype for these IL9 polymorphisms were more likely to report a severe asthma exacerbation if exposed to increased dust mite levels. CONCLUSIONS: Genome-wide differential gene expression in response to dust mite allergen identified IL9, a biologically plausible gene target that might interact with environmental dust mite to increase severe asthma exacerbations in children.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/genética , Asma/imunologia , Cisteína Endopeptidases/imunologia , Dermatophagoides farinae/imunologia , Interação Gene-Ambiente , Interleucina-9/genética , Leucócitos Mononucleares/fisiologia , Animais , Células Cultivadas , Criança , Pré-Escolar , Estudos de Coortes , Costa Rica , Progressão da Doença , Serviços Médicos de Emergência , Exposição Ambiental/efeitos adversos , Proteína Básica Maior de Eosinófilos/genética , Proteína Básica Maior de Eosinófilos/metabolismo , Feminino , Seguimentos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Interleucina-5/genética , Interleucina-5/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único , Proteoglicanas/genética , Proteoglicanas/metabolismo , Porto Rico , Transcriptoma , Estados Unidos , Regulação para Cima
9.
Ann Allergy Asthma Immunol ; 115(4): 288-293.e1, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26319606

RESUMO

BACKGROUND: Dietary patterns might influence the pathogenesis of asthma in Puerto Ricans, the ethnic group most affected by this disease in the United States. OBJECTIVE: To examine the association among diet, T-helper cell type 17 cytokines, and asthma in Puerto Rican children. METHODS: As part of a case-control study of 678 Puerto Rican children 6 to 14 years old in San Juan, participants completed a 75-item questionnaire on the child's food consumption in the prior week. Foods were aggregated into 7 groups: fruits, vegetables, grains, protein foods, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group, plasma T-helper cell type 17 cytokine levels, and asthma. Based on this analysis, a food score (range -2 [unhealthy diet: high consumption of dairy products and sweets, low consumption of vegetables and grains] to +2 [healthy diet: high consumption of grains and vegetables, low consumption of dairy and sweets]) was created to identify dietary patterns. RESULTS: High consumption of grains was associated with lower odds of asthma (adjusted odds ratio [aOR] 0.52, 95% confidence interval [CI] 0.33-0.82), whereas frequent consumption of dairy products (aOR 1.93, 95% CI 1.32-2.84) or sweets (aOR 1.82, 95% CI 1.08-2.72) was associated with higher odds of asthma. A healthier diet (each 1-point increment in food score) was associated with lower levels of interleukin-17F (ß = -1.48 pg/mL, 95% CI -1.78 to -1.20) and with 36% decreased odds of asthma (aOR 0.64, 95% CI 0.53-0.77). CONCLUSION: A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with lower levels of interleulin-17F and decreased odds of childhood asthma in Puerto Ricans.


Assuntos
Asma/sangue , Asma/epidemiologia , Dieta/métodos , Comportamento Alimentar , Interleucina-17/sangue , Adolescente , Estudos de Casos e Controles , Criança , Laticínios , Grão Comestível , Feminino , Frutas , Humanos , Masculino , Porto Rico/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Células Th17/imunologia , Verduras
10.
J Allergy Clin Immunol ; 134(5): 1009-15, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25129683

RESUMO

In the United States the economically disadvantaged and some ethnic minorities are often exposed to chronic psychosocial stressors and disproportionately affected by asthma. Current evidence suggests a causal association between chronic psychosocial stress and asthma or asthma morbidity. Recent findings suggest potential mechanisms underlying this association, including changes in the methylation and expression of genes that regulate behavioral, autonomic, neuroendocrine, and immunologic responses to stress. There is also evidence suggesting the existence of susceptibility genes that predispose chronically stressed youth to both post-traumatic stress disorder and asthma. In this review we critically examine published evidence and suggest future directions for research in this field.


Assuntos
Asma , Epigênese Genética/imunologia , Predisposição Genética para Doença , Transtornos de Estresse Pós-Traumáticos , Estresse Psicológico , Asma/etiologia , Asma/genética , Asma/imunologia , Asma/mortalidade , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/imunologia , Transtornos de Estresse Pós-Traumáticos/mortalidade , Estresse Psicológico/complicações , Estresse Psicológico/genética , Estresse Psicológico/imunologia , Estresse Psicológico/mortalidade , Estados Unidos
11.
J Allergy Clin Immunol ; 133(5): 1308-14, 1314.e1-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24290290

RESUMO

BACKGROUND: Whether adiposity indicators other than body mass index (BMI) should be used in studies of childhood asthma is largely unknown. The role of atopy in "obese asthma" is also unclear. OBJECTIVES: To examine the relationship among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. METHODS: In a study of Puerto Rican children with (n = 351) and without (n = 327) asthma, we measured BMI, percent of body fat, waist circumference, and waist-to-hip ratio. The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. RESULTS: BMI, percent of body fat, and waist circumference were associated with increased odds of asthma. Among cases, all 3 measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22% to 53% of the association with asthma, and sensitization to cockroach mediated 13% to 20% of the association with forced vital capacity and 29% to 42% of the association with emergency department visits for asthma. CONCLUSIONS: Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on "obese asthma" in childhood.


Assuntos
Adiposidade , Asma , Obesidade , Rinite Alérgica Perene , Adolescente , Asma/complicações , Asma/patologia , Asma/fisiopatologia , Índice de Massa Corporal , Criança , Feminino , Hispânico ou Latino , Humanos , Masculino , Obesidade/complicações , Obesidade/patologia , Obesidade/fisiopatologia , Porto Rico , Testes de Função Respiratória , Rinite Alérgica , Rinite Alérgica Perene/complicações , Rinite Alérgica Perene/patologia , Rinite Alérgica Perene/fisiopatologia , Circunferência da Cintura , Relação Cintura-Quadril
12.
J Allergy Clin Immunol ; 133(2): 357-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24139607

RESUMO

BACKGROUND: Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. OBJECTIVE: We sought to examine whether prematurity is associated with asthma in Puerto Rican children. METHODS: We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. RESULTS: In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. CONCLUSIONS: Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group.


Assuntos
Asma/epidemiologia , Hipersensibilidade/epidemiologia , Nascimento Prematuro/epidemiologia , Adolescente , Asma/etnologia , Estudos de Casos e Controles , Criança , Feminino , Hispânico ou Latino , Humanos , Hipersensibilidade/etnologia , Recém-Nascido Prematuro , Masculino , Gravidez , Nascimento Prematuro/etnologia
13.
N Engl J Med ; 364(10): 897-906, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21388308

RESUMO

BACKGROUND: Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. METHODS: We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. RESULTS: Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. CONCLUSIONS: In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).


Assuntos
Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/patologia , Fumar/patologia , Capacidade Pulmonar Total , Estudos de Coortes , Humanos , Modelos Lineares , Modelos Logísticos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/etiologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/etiologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Fumar/efeitos adversos , Espirometria , Tomografia Computadorizada por Raios X/métodos
14.
Ann Allergy Asthma Immunol ; 113(6): 614-618.e2, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25304339

RESUMO

BACKGROUND: Little is known about exposure to mouse allergen (Mus m 1) and allergic rhinitis (AR). OBJECTIVE: To evaluate the association between mouse allergen exposure and AR in children. METHODS: We examined the relation between mouse allergen level in house dust and AR in 511 children aged 6 to 14 years in San Juan, Puerto Rico. Study participants were chosen from randomly selected households using a multistage probability sample design. The study protocol included questionnaires, allergy skin testing, and collection of blood and dust samples. AR was defined as current rhinitis symptoms and skin test reactivity to at least one allergen. RESULTS: In the multivariate analyses, mouse allergen level was associated with a 25% decreased odds of AR in participating children (95% confidence interval, 0.62-0.92). Although endotoxin and mouse allergen levels were significantly correlated (r = 0.184, P < .001), the observed inverse association between Mus m 1 and AR was not explained by levels of endotoxin or other markers of microbial or fungal exposure (peptidoglycan and glucan). CONCLUSION: Mouse allergen exposure is associated with decreased odds of AR in Puerto Rican school-aged children.


Assuntos
Poluição do Ar em Ambientes Fechados , Alérgenos/imunologia , Asma/imunologia , Poeira/imunologia , Rinite Alérgica/imunologia , Adolescente , Animais , Asma/complicações , Asma/diagnóstico , Criança , Endotoxinas/imunologia , Feminino , Humanos , Masculino , Camundongos , Razão de Chances , Porto Rico , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Testes Cutâneos , Inquéritos e Questionários
15.
Curr Allergy Asthma Rep ; 14(9): 461, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25086579

RESUMO

The vitamin D hypothesis postulates that lower vitamin D levels are causally associated with increased asthma risk and asthma severity. Multiple epidemiological studies have shown an inverse relationship between circulating vitamin D levels (in the form of 25-hydroxy vitamin D) and asthma severity and control and lung function. However, in the recently published vitamin D and asthma (VIDA) study, vitamin D supplementation failed to show an improvement in asthma control in adults. This article reviews the current epidemiological and trial evidence for vitamin D and asthma and explores some of the possible alternative explanations for previous findings (including "reverse causation" and the importance of studying children and adults). We also address some of the unique challenges of conducting vitamin D trials and potential ways to address them. Finally, I will argue for further clinical trials of vitamin D in asthma, especially in children, using knowledge gained from the VIDA trial.


Assuntos
Asma/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Asma/tratamento farmacológico , Criança , Suplementos Nutricionais , Humanos , Vitamina D/sangue , Vitamina D/metabolismo , Vitaminas/metabolismo
16.
J Chem Phys ; 141(20): 204704, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25429954

RESUMO

We calculate the shift current response, which has been identified as the dominant mechanism for the bulk photovoltaic effect, for the polar compounds LiAsS2, LiAsSe2, and NaAsSe2. We find that the magnitudes of the photovoltaic responses in the visible range for these compounds exceed the maximum response obtained for BiFeO3 by 10-20 times. We correlate the high shift current response with the existence of p states at both the valence and conduction band edges, as well as the dispersion of these bands, while also showing that high polarization is not a requirement. With low experimental band gaps of less than 2 eV and high shift current response, these materials have potential for use as bulk photovoltaics.

17.
J Chem Phys ; 140(22): 224703, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24929410

RESUMO

We use first-principles density functional theory within the local density approximation to ascertain the ground state structure of real and theoretical compounds with the formula ABS3 (A = K, Rb, Cs, Ca, Sr, Ba, Tl, Sn, Pb, and Bi; and B = Sc, Y, Ti, Zr, V, and Nb) under the constraint that B must have a d(0) electronic configuration. Our findings indicate that none of these AB combinations prefer a perovskite ground state with corner-sharing BS6 octahedra, but that they prefer phases with either edge- or face-sharing motifs. Further, a simple two-dimensional structure field map created from A and B ionic radii provides a neat demarcation between combinations preferring face-sharing versus edge-sharing phases for most of these combinations. We then show that by modifying the common Goldschmidt tolerance factor with a multiplicative term based on the electronegativity difference between A and S, the demarcation between predicted edge-sharing and face-sharing ground state phases is enhanced. We also demonstrate that, by calculating the free energy contribution of phonons, some of these compounds may assume multiple phases as synthesis temperatures are altered, or as ambient temperatures rise or fall.

18.
Am J Respir Crit Care Med ; 188(1): 12-7, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23650899

RESUMO

Findings from experimental studies and animal models led to the hypothesis that folic acid supplementation during pregnancy confers an increased risk of asthma. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between folate status and asthma. In industrialized nations, the prevalence of asthma was rising before widespread fortification of foodstuffs with folic acid or folate supplementation before or during pregnancy, thus suggesting that changes in folate status are an unlikely explanation for "the asthma epidemic." Consistent with this ecologic observation, evidence from human studies does not support moderate or strong effects of folate status on asthma. Given known protective effects against neural tube and cardiac defects, there is no reason to alter current recommendations for folic acid supplementation during conception or pregnancy based on findings for folate and asthma. Although we believe that there are inadequate data to exclude a weak effect of maternal folate status on asthma or asthma symptoms, such effects could be examined within the context of very large (and ongoing) birth cohort studies. At this time, there is no justification for funding new studies of folate and asthma.


Assuntos
Asma/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Gravidez
19.
Am J Respir Crit Care Med ; 187(6): 584-8, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23328528

RESUMO

RATIONALE: Epigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children. OBJECTIVES: To examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans. METHODS: We conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter of ADCYAP1R1 (cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components. MEASUREMENTS AND MAIN RESULTS: EACH 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6; P = 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67; P = 0.03). CONCLUSIONS: Epigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.


Assuntos
Asma/genética , Variação Genética/genética , Hispânico ou Latino/genética , Adolescente , Estudos de Casos e Controles , Criança , Ilhas de CpG/genética , Metilação de DNA/genética , Epigênese Genética , Feminino , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologia , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase
20.
Am J Respir Crit Care Med ; 185(2): 124-32, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22016447

RESUMO

Vitamin D deficiency and asthma are common conditions that share risk factors such as African American ethnicity, inner-city residence, and obesity. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between vitamin D status and asthma or asthma morbidity, including potential protective mechanisms such as antiviral effects and enhanced steroid responsiveness. Because most published epidemiologic studies of vitamin D and asthma or asthma morbidity are observational, a recommendation for or against vitamin D supplementation as preventive or secondary treatment for asthma is not advisable and must await results of ongoing clinical trials. Should these trials confirm a beneficial effect of vitamin D, others will be needed to assess the role of vitamin D supplementation to prevent or treat asthma in different groups such as infants, children of school age, and ethnic minorities.


Assuntos
Asma/epidemiologia , Deficiência de Vitamina D/epidemiologia , Asma/tratamento farmacológico , Asma/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Medicina Baseada em Evidências , Humanos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
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