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2.
Nat Commun ; 10(1): 880, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787307

RESUMO

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.


Assuntos
Afro-Americanos/genética , Asma/genética , Predisposição Genética para Doença/genética , Asma/epidemiologia , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 8/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Hispano-Americanos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-30562990

RESUMO

Cooking with kerosene emits toxic pollutants that may impact pregnancy outcomes. Sixty-eight women in their first trimester of pregnancy, kerosene users (n = 42) and liquefied natural gas (LNG) users (n = 26), were followed until birth. Maternal and cord blood were collected immediately after birth. Levels of micronutrients and heavy metals were quantified. Pregnancy outcomes (gestation age (GA), birth weight (BW), and chest and head circumference) were also measured. Mean (± standard deviation (SD)) age of mothers in kerosene and LNG groups were similar (p = 0.734). Mean (±SD) BW of newborns of LNG users was significantly higher compared to newborns of kerosene users (3.43 ± 0.32 vs. 3.02 ± 0.43, p < 0.001). Mean GA (in weeks) was similar between the two groups (p = 0.532). Women in the kerosene group had significantly higher cord blood levels of zinc, lead, mercury, iodine and vitamin B6 and lower levels of folic acid compared to LNG users (p < 0.05). Newborns of kerosene users had reduced levels of zinc, lead, mercury, iodine, vitamins B6 and B12, folic acid, and homocysteine compared with LNG users (p < 0.05). Also, cooking with kerosene was significantly associated with reduced birth weight after adjusting for potential confounders (ß ± standard error (SE) = -0.326 ± 0.155; p = 0.040). Smoke from kerosene stove was associated with reduced birth weight and micronutrients imbalance in mothers and newborns.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Culinária/métodos , Metais Pesados/sangue , Micronutrientes/sangue , Resultado da Gravidez/epidemiologia , Adulto , Fatores Etários , Peso ao Nascer , Pesos e Medidas Corporais , Estudos Transversais , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Recém-Nascido , Querosene , Mães , Gravidez
6.
Nat Genet ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30455414

RESUMO

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

7.
Nat Commun ; 9(1): 4181, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327465

RESUMO

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

8.
Sci Total Environ ; 619-620: 212-220, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29149745

RESUMO

BACKGROUND: Household air pollution (HAP) is associated with adverse pregnancy outcomes. OBJECTIVES: Investigate impact of in-utero HAP exposure on placental development and chronic hypoxia. METHODS: Markers of chronic placental hypoxia [Hofbauer cells (HBC), syncytial knots (SK), chorionic vascular density (cVD) and hypoxia-inducible factor (HIF)] were stained by hematoxylin-eosin and/or immunohistochemically in placenta samples collected from firewood-/kerosene-users (A,n=16), and ethanol-users (B,n=20) that participated in a randomized controlled intervention trial in Ibadan, Nigeria. A third group of non-smoking and presumed natural gas-using Chicago women (C,n=12) were included in this exploratory pilot to assess for possible differences in placenta histology between similar racial groups. All patients had uncomplicated pregnancies and delivered at term. RESULTS: HBC, SK and cVD were significantly increased among firewood-/kerosene-users compared to ethanol-users and natural gas-using Chicago women (HBC medians 5.5, 3.5, and 2.0, respectively; SK means 55.6, 41.8 and 30.1; cVD means 8.8, 6.2, and 5.2; all p<0.01). HIF expression was significantly higher in Group A compared to B and C (all p<0.001). CONCLUSIONS: In-utero exposure to HAP is associated with pathologic changes and HIF expression consistent with chronic hypoxia in placenta of firewood/kerosene-users compared to ethanol-users with less HAP exposure and Chicago women with no presumed HAP exposure. Presence of chronic hypoxic signature in placenta of women exposed to HAP has implications for adverse pregnancy complications and future growth and development of the young children. Future larger studies need to focus on HAP exposure and placental disorders like preeclampsia and long-term health impact of in-utero exposure to HAP.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Culinária/instrumentação , Hipóxia/epidemiologia , Placenta/efeitos dos fármacos , Adulto , Chicago , Etanol , Feminino , Humanos , Nigéria , Placenta/fisiopatologia , Gravidez , Resultado da Gravidez , Adulto Jovem
9.
Environ Int ; 111: 152-163, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29216559

RESUMO

BACKGROUND: Household air pollution (HAP) exposure has been linked to adverse pregnancy outcomes. OBJECTIVES: A randomized controlled trial was undertaken in Ibadan, Nigeria to determine the impact of cooking with ethanol on pregnancy outcomes. METHODS: Three-hundred-twenty-four pregnant women were randomized to either the control (continued cooking using kerosene/firewood stove, n=162) or intervention group (received ethanol stove, n=162). Primary outcome variables were birthweight, preterm delivery, intrauterine growth restriction (IUGR), and occurrence of miscarriage/stillbirth. RESULTS: Mean birthweights for ethanol and controls were 3076 and 2988g, respectively; the difference, 88g, (95% confidence interval: -18g to 194g), was not statistically significant (p=0.10). After adjusting for covariates, the difference reached significance (p=0.020). Rates of preterm delivery were 6.7% (ethanol) and 11.0% (control), (p=0.22). Number of miscarriages was 1(ethanol) vs. 4 (control) and stillbirths was 3 (ethanol) vs. 7 (control) (both non-significant). Average gestational age at delivery was significantly (p=0.015) higher in ethanol-users (39.2weeks) compared to controls (38.2weeks). Perinatal mortality (stillbirths and neonatal deaths) was twice as high in controls compared to ethanol-users (7.9% vs. 3.9%; p=0.045, after adjustment for covariates). We did not detect significant differences in exposure levels between the two treatment arms, perhaps due to large seasonal effects and high ambient air pollution levels. CONCLUSIONS: Transition from traditional biomass/kerosene fuel to ethanol reduced adverse pregnancy outcomes. However, the difference in birthweight was statistically significant only after covariate adjustment and the other significant differences were in tertiary endpoints. Our results are suggestive of a beneficial effect of ethanol use. Larger trials are required to validate these findings.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Culinária/métodos , Etanol , Utensílios Domésticos , Resultado da Gravidez , Adolescente , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Peso ao Nascer , Monóxido de Carbono/análise , Monitoramento Ambiental , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Querosene , Nigéria , Material Particulado/análise , Gravidez , Nascimento Prematuro/induzido quimicamente , Madeira , Adulto Jovem
10.
Sci Total Environ ; 599-600: 2175-2181, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575932

RESUMO

BACKGROUND: Maternal exposure to ambient air pollution affects placental growth markers. OBJECTIVES: Investigate impact of household air pollution (HAP) on placental growth markers. METHODS: Two groups of pregnant women were identified: firewood/kerosene stove-users (A, n=33) and bioethanol stove-users (B, n=44) that participated in a randomized control trial in Ibadan, Nigeria. A third group of non-smoking and presumed liquefied petroleum gas-using Chicago women (C, n=19) were included in this exploratory pilot to assess for possible differences between similar racial groups. Levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured in maternal and cord plasma using ELISA. RESULTS: Maternal and cord blood sFlt-1 and PlGF did not differ significantly between women of groups A and B. Nevertheless, both groups differed significantly from the Chicago group in that group A women had lower maternal sFlt-1 (1372.50 vs. 3194.19) but higher PlGF (1607.87 vs. 442.80), and higher cord blood sFlt-1 (2925.02 vs. 107.53) and PlGF (223.68 vs. 6.92), all p≤0.001. Group B showed similar trends (all p≤0.002). Maternal PlGF levels were positively correlated to minutes of HAP exposure when PM2.5 concentration was above 100µg/m3 in Nigerian women. CONCLUSIONS: Maternal levels of PlGF and cord blood levels of sFlt-1 and PlGF in Nigerian women with varying HAP exposures were significantly higher than Chicago-based women who had no presumed HAP exposure. It suggests that in-utero exposure to HAP influenced levels of angiogenic factors involved in normal placentation and growth and could represent compensation for pollutants exposure to preserve fetal viability.


Assuntos
Poluição do Ar/análise , Culinária/instrumentação , Exposição Materna , Fator de Crescimento Placentário/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Biomarcadores/sangue , Chicago , Etanol , Feminino , Sangue Fetal/química , Humanos , Nigéria , Gravidez
11.
Am J Respir Crit Care Med ; 195(12): 1629-1639, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28081369

RESUMO

RATIONALE: Hypertension during pregnancy is a leading cause of maternal mortality. Exposure to household air pollution elevates blood pressure (BP). OBJECTIVES: To investigate the ability of a clean cookstove intervention to lower BP during pregnancy. METHODS: We conducted a randomized controlled trial in Nigeria. Pregnant women cooking with kerosene or firewood were randomly assigned to an ethanol arm (n = 162) or a control arm (n = 162). BP measurements were taken during six antenatal visits. In the primary analysis, we compared ethanol users with control subjects. In subgroup analyses, we compared baseline kerosene users assigned to the intervention with kerosene control subjects and compared baseline firewood users assigned to ethanol with firewood control subjects. MEASUREMENTS AND MAIN RESULTS: The change in diastolic blood pressure (DBP) over time was significantly different between ethanol users and control subjects (P = 0.040); systolic blood pressure (SBP) did not differ (P = 0.86). In subgroup analyses, there was no significant intervention effect for SBP; a significant difference for DBP (P = 0.031) existed among preintervention kerosene users. At the last visit, mean DBP was 2.8 mm Hg higher in control subjects than in ethanol users (3.6 mm Hg greater in control subjects than in ethanol users among preintervention kerosene users), and 6.4% of control subjects were hypertensive (SBP ≥140 and/or DBP ≥90 mm Hg) versus 1.9% of ethanol users (P = 0.051). Among preintervention kerosene users, 8.8% of control subjects were hypertensive compared with 1.8% of ethanol users (P = 0.029). CONCLUSIONS: To our knowledge, this is the first cookstove randomized controlled trial examining prenatal BP. Ethanol cookstoves have potential to reduce DBP and hypertension during pregnancy. Accordingly, clean cooking fuels may reduce adverse health impacts associated with household air pollution. Clinical trial registered with www.clinicaltrials.gov (NCT02394574).


Assuntos
Pressão Sanguínea , Culinária/instrumentação , Culinária/métodos , Etanol , Hipertensão/prevenção & controle , Complicações Cardiovasculares na Gravidez/prevenção & controle , Adulto , Feminino , Humanos , Querosene/efeitos adversos , Nigéria , Gravidez , Madeira/efeitos adversos
12.
BMC Pulm Med ; 17(1): 3, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056916

RESUMO

BACKGROUND: In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. METHODS: Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. RESULTS: A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). CONCLUSION: In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/epidemiologia , Exposição Ambiental/efeitos adversos , Adolescente , Biomassa , Criança , Culinária , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Morbidade , Análise Multivariada , Nigéria/epidemiologia , Sons Respiratórios/etiologia , Fatores de Risco , População Rural
13.
J Asthma ; 54(4): 347-356, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27589676

RESUMO

BACKGROUND: Approximately 70% of rural Nigerian households rely on biomass fuels for cooking. The International Study of Asthma and Allergies in Childhood (ISAAC) estimates the prevalence of current wheeze among children in Nigeria to have risen from 10.7% in 1999 to approximately 20% in 2014. OBJECTIVE: To examine the effects of biomass smoke exposure on asthma symptom prevalence in rural children in Nigeria. METHODS: We conducted a cross-sectional survey in rural communities in Nigeria. Asthma symptoms were defined according to ISAAC definitions. Biomass smoke exposure was determined by the types of fuel used for cooking. Logistic regression was used to explore associations between biomass smoke and asthma symptoms. RESULTS: The study population comprised 1,690 school children, of which 865 lived in households cooking with biomass and 825 lived in households not using biomass. Asthma symptoms were reported in 481 (28.5%) children. Biomass fuel was associated with increased odds of asthma symptoms. Adjusted odds ratios (aORs) were 1.38 (95% CI: 1.05-1.80) for nocturnal cough, 1.26 (95% CI: 1.00-1.61) for current wheeze, and 1.33 (95% CI: 1.05-1.69) for report of any asthma-related symptoms. Sex modified the associations between asthma symptoms with biomass fuel: aORs were stronger and significant for males (nocturnal cough = 1.85, 95% CI: 1.24-2.76; current wheeze = 1.48, 95% CI: 1.03-2.13; report of any asthma-related symptoms = 1.60, 95% CI: 1.12-2.28), but weaker and non-significant for females. CONCLUSION: The risk of asthma symptoms related to biomass smoke exposure appears to differ by sex.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/epidemiologia , Culinária/métodos , População Rural/estatística & dados numéricos , Fumaça/efeitos adversos , Adolescente , Criança , Tosse , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Nigéria/epidemiologia , Prevalência , Sons Respiratórios , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
14.
Environ Int ; 98: 181-190, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27839852

RESUMO

BACKGROUND: Exposure to household air pollution (HAP) has been linked to systemic inflammation. We determined the impact of transition from traditional firewood/kerosene stove to bioethanol-burning stove on inflammatory biomarkers in pregnant Nigerian women. METHODS: Women (n=324), cooking with kerosene/firewood, were recruited during their first trimester of pregnancy from June 2013-October 2015 and were randomly allocated to either control (n=162) or intervention (n=162) group using web-based randomization. Controls continued to use their own firewood/kerosene stove, while intervention participants received bioethanol CleanCook stoves. Serum concentrations of retinol-binding protein (RBP), malondialdehyde (MDA), tumor necrosis factor alpha (TNF)-α, interleukin (IL)-6, and IL-8 were measured by ELISA. RESULTS: After excluding 53 women (loss of follow-up, untimely biomarker assessments, incorrect dates of enrollment), data from 271 women were included in analysis. Mean (SD) change in RBP, MDA, TNF-α, IL-6, and IL-8 between baseline and third trimester was -2.16 (4.47), -19.6 (46.4), 3.72 (37.2), 0.51 (14.4), and 13.2 (197), respectively, in intervention and -2.25 (4.30), -24.6 (43.6), 7.17 (32.6), -1.79, (11.4), and 31.3 (296) in control groups. None of these changes differed significantly between the two treatment arms. However, changes from baseline in TNF-α levels were significantly different between intervention and control groups in subset of women (n=99) using firewood before trial (-7.03 [32.9] vs. +12.4 [33.6]; 95% CI for group difference: -35.4 to -3.4, p=0.018). CONCLUSIONS: Decrease in TNF-α concentration from baseline to third trimesters in intervention group women could indicate reduced cardiovascular stress and prothrombotic effects from decreased HAP. Our findings suggest that ethanol-burning stoves may mitigate cardiovascular health risks.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Biomarcadores/sangue , Culinária/instrumentação , Inflamação/sangue , Estresse Oxidativo , Adolescente , Adulto , Poluição do Ar , Poluição do Ar em Ambientes Fechados/efeitos adversos , Biocombustíveis , Etanol , Feminino , Utensílios Domésticos , Produtos Domésticos , Humanos , Inflamação/etiologia , Interleucina-6 , Querosene , Nigéria , Gravidez , Gestantes/etnologia , Adulto Jovem
15.
Glob Health Action ; 9: 31026, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27178644

RESUMO

BACKGROUND: The poor genomics research capacity of Sub-Saharan Africa (SSA) could prevent maximal benefits from the applications of genomics in the practice of medicine and research. The objective of this study is to examine the author affiliations of genomic epidemiology publications in order to make recommendations for building local genomics research capacity in SSA. DESIGN: SSA genomic epidemiology articles published between 2004 and 2013 were extracted from the Human Genome Epidemiology (HuGE) database. Data on authorship details, country of population studied, and phenotype or disease were extracted. Factors associated with the first author, who has an SSA institution affiliation (AIAFA), were determined using a Chi-square test and multiple logistic regression analysis. RESULTS: The most commonly studied population was South Africa, accounting for 31.1%, followed by Ghana (10.6%) and Kenya (7.5%). About one-tenth of the papers were related to non-communicable diseases (NCDs) such as cancer (6.1%) and cardiovascular diseases (CVDs) (4.3%). Fewer than half of the first authors (46.9%) were affiliated with an African institution. Among the 238 articles with an African first author, over three-quarters (79.8%) belonged to a university or medical school, 16.8% were affiliated with a research institute, and 3.4% had affiliations with other institutions. CONCLUSIONS: Significant disparities currently exist among SSA countries in genomics research capacity. South Africa has the highest genomics research output, which is reflected in the investments made in its genomics and biotechnology sector. These findings underscore the need to focus on developing local capacity, especially among those affiliated with SSA universities where there are more opportunities for teaching and research.


Assuntos
Bibliometria , Pesquisa Biomédica , Fortalecimento Institucional , Genômica , Epidemiologia Molecular , África ao Sul do Saara , Países em Desenvolvimento , Humanos , Faculdades de Medicina , Universidades
16.
Nat Rev Clin Oncol ; 11(5): 251-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24614139

RESUMO

Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced-based cancer control approaches and planning at the local, regional and national levels.


Assuntos
Pesquisa Biomédica/organização & administração , Oncologia/organização & administração , África , Participação da Comunidade , Ética em Pesquisa , Fundações/organização & administração , Órgãos Governamentais/organização & administração , Humanos , Agências Internacionais/organização & administração , Cooperação Internacional , Oncologia/educação , National Cancer Institute (U.S.) , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Neoplasias/terapia , Parcerias Público-Privadas , Sistema de Registros , Apoio à Pesquisa como Assunto , Estados Unidos , Universidades/organização & administração
17.
J Biomark ; 2014: 106150, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26317027

RESUMO

Objective. Increasing prevalence of asthma has been attributed to changes in lifestyle and environmental exposures. We conducted a case-control study to investigate the relationship between serum micronutrients and asthma in rural school children in Nigeria. Methods. We administered questionnaires to 1,562 children to identify children with asthma. Serum concentration levels of 12 micronutrients were determined in asthma cases (N = 37) and controls (N = 30). Allergy skin prick test and spirometry were also performed. Results. Plasma levels of the following micronutrients were significantly different between cases and controls: calcium (7.48 ± 2.16 versus 8.29 ± 1.62 mg/dL; P = 0.04), manganese (44.1 ± 11.5 versus 49.3 ± 7.9 mg/L; P = 0.01), selenium (76.1 ± 14.9 versus 63.3 ± 26.8 µg/L; P = 0.02), and albumin (3.45 ± 0.90 versus 3.91 ± 0.99 g/dL; P = 0.04). Plasma concentrations of iron and selenium were positively correlated with lung function, r = 0.43 (P < 0.05 in each case) while manganese serum concentration was negatively correlated with asthma (r = -0.44; P < 0.05). Conclusions. Children with asthma had reduced levels of plasma manganese, calcium, and albumin but raised level of selenium. The protective or risk effects of these micronutrients on asthma warrant further investigation.

18.
Carcinogenesis ; 34(7): 1520-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23475944

RESUMO

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Adulto , Alelos , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/metabolismo , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 6/metabolismo , Intervalos de Confiança , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
19.
J Asthma ; 45(3): 183-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18415823

RESUMO

RATIONALE: Previous studies have suggested that asthmatics have an increased incidence of sleep disturbances. However, these studies have been limited by reliance on population surveys or small numbers of participants. OBJECTIVES: We sought to measure sleep quality and daytime sleepiness in a cohort of symptomatic asthmatics and to measure the effects of improved asthma control on sleep quality. METHODS: Data were collected in sub-study of a large multi-center randomized double-masked controlled trial of mild-moderate asthmatics evaluating the effect of low-dose theophylline on asthma control in comparison to montelukast and placebo. Each participant was administered sleep symptom questionnaires at randomization and at the final visit (6 months after randomization). These included the Pittsburgh Sleep Quality Questionnaire (PSQI) and the Epworth Sleepiness Scale (ESS). MEASUREMENTS AND MAIN RESULTS: Data were available for 487 participants. Baseline mean values were: age 40 +/- 15 years, 74% female, forced expiratory volume in 1 second (FEV(1)) 79 +16 percent predicted, Juniper Asthma Control Questionnaire (ACQ) score 2.35 +/- 0.63, PSQI 7.8 +/-4, and ESS 8.5 +/-4.9. There were no significant differences in the PSQI or ESS between the three treatment groups. Significant correlations were found at baseline between the global PSQI score and ACQ and quality of life and marginally with lung function. Significant correlation existed between improvements in PSQI and ESS with improved asthma control and quality of life. CONCLUSIONS: Sleep disturbances are common in asthmatics and are associated with asthma control and quality of life. Clinicians caring for asthmatics may need to complete a more detailed sleep history in patients with poorly controlled asthma. In addition, low-dose theophylline does not seem to impair sleep quality in asthmatics.


Assuntos
Asma/complicações , Transtornos do Sono-Vigília/etiologia , Acetatos/uso terapêutico , Adulto , Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Masculino , Qualidade de Vida , Quinolinas/uso terapêutico , Testes de Função Respiratória , Transtornos do Sono-Vigília/fisiopatologia , Inquéritos e Questionários , Teofilina/uso terapêutico
20.
Sleep ; 30(12): 1747-55, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18246984

RESUMO

STUDY OBJECTIVES: Recurrent apneas and hypoxemia during sleep in obstructive sleep apnea (OSA) are associated with profound changes in cerebral blood flow to the extent that cerebral autoregulation may be insufficient to protect the brain. Since the brain is sensitive to hypoxia, the cerebrovascular morbidity seen in OSA could be due to chronic, cumulative effects of intermittent hypoxia. Near-infrared spectroscopy (NIRS) has the potential to noninvasively monitor brain tissue oxygen saturation (SO2), and changes in concentration of oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb] and total hemoglobin [tHb] with real-time resolution. We hypothesized that brain tissue oxygenation would be worse during sleep in OSA relative to controls and sought to determine the practical use of NIRS in the sleep laboratory. DESIGN: We evaluated changes in brain tissue oxygenation using NIRS during overnight polysomnography. SETTING: Studies were conducted at University of Illinois, Chicago and Carle Hospital, Urbana, Illinois. PATIENTS: Nineteen subjects with OSA and 14 healthy controls underwent continuous NIRS monitoring during polysomnography. MEASUREMENTS AND RESULTS: We observed significantly lower indexes of brain tissue oxygenation (SO2: 57.1 +/- 4.9 vs. 61.5 +/- 6.1), [O2Hb]: 22.8 +/- 7.7 vs. 31.5 +/- 9.1, and [tHb]: 38.6 +/- 11.2 vs. 48.6 +/- 11.4 micromol/L) in OSA than controls (all P < 0.05). However, multivariate analysis showed that the differences might be due to age disparity between the two groups. CONCLUSIONS: NIRS is an effective tool to evaluate brain tissue oxygenation in OSA. It provides valuable data in OSA assessment and has the potential to bridge current knowledge gap in OSA.


Assuntos
Encéfalo/fisiopatologia , Consumo de Oxigênio/fisiologia , Processamento de Sinais Assistido por Computador/instrumentação , Apneia Obstrutiva do Sono/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Adulto , Fatores Etários , Índice de Massa Corporal , Apresentação de Dados , Feminino , Hemoglobinometria , Hemoglobinas/metabolismo , Humanos , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxiemoglobinas/metabolismo , Polissonografia , Valores de Referência , Análise de Regressão , Sensibilidade e Especificidade , Apneia Obstrutiva do Sono/diagnóstico , Software
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