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2.
PLoS Genet ; 13(5): e1006728, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28498854

RESUMO

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.


Assuntos
Pressão Sanguínea/genética , Loci Gênicos , Hipertensão/genética , Herança Multifatorial , Negro ou Afro-Americano/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Caderinas/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/etnologia , Masculino , Proteínas de Membrana/genética , Camundongos , Polimorfismo de Nucleotídeo Único
3.
Orbit ; 38(2): 87-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29517388

RESUMO

The purpose is to evaluate the utility of optical coherence tomography (OCT) angiography in the evaluation of Graves' orbitopathy (GO) and response to orbital decompression in patients with and without dysthyroid optic neuropathy (DON). This was a single-center, prospective case series in a cohort of 12 patients (24 orbits) with GO and ±DON, (6 orbits) who underwent bilateral orbital decompression. All patients underwent pre- and postoperative OCT angiography of the peripapillary area. Vessel density indices were calculated in a 4.5 mm × 4.5 mm ellipsoid centered on the optic disk using split-spectrum amplitude decorrelation angiography algorithm, producing the vessel density measurements. Mean change in vessel density indices was compared between pre- and postoperative sessions and between patients with and without DON. Patient 1, a 34-year-old male with GO and unilateral DON OD, showed a significant reduction in blood vessel density indices oculus dexter (OD) (DON eye) after decompression while a more modest reduction was found oculus sinister (OS) with the greatest change noted intrapapillary. Patient 2, a 50-year-old male with DON OU, showed worsening neuropathy following decompression OD that was confirmed by angiographic density indices. Patient 3, a 55-year-female with DON, showed a reduction in blood vessel density OD and increased density OS. Patients without DON showed overall less impressive changes in indices as compared to those with DON. Using OCT angiography, response to surgical treatment in GO orbits, more so in orbits with DON, can be demonstrated and quantified using vessel density indices with reproducibility.


Assuntos
Vasos Sanguíneos/patologia , Descompressão Cirúrgica/métodos , Oftalmopatia de Graves/fisiopatologia , Oftalmopatia de Graves/cirurgia , Disco Óptico/irrigação sanguínea , Órbita/cirurgia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Artérias Ciliares/patologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/patologia , Procedimentos Cirúrgicos Oftalmológicos , Estudos Prospectivos , Fluxo Sanguíneo Regional , Vasos Retinianos/patologia
4.
Alzheimers Dement ; 14(2): 167-177, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28916238

RESUMO

INTRODUCTION: Existing studies predominantly consider the association of late-life lipid levels and subsequent cognitive change. However, midlife rather than late-life risk factors are often most relevant to cognitive health. METHODS: We quantified the association between measured serum lipids in midlife and subsequent 20-year change in performance on three cognitive tests in 13,997 participants of the Atherosclerosis Risk in Communities study. RESULTS: Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides were associated with greater 20-year decline on a test of executive function, sustained attention, and processing speed. Higher total cholesterol and triglycerides were also associated with greater 20-year decline in memory scores and a measure summarizing performance on all three tests. High-density lipoprotein cholesterol was not associated with cognitive change. Results were materially unchanged in sensitivity analyses addressing informative missingness. DISCUSSION: Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20-year cognitive decline.


Assuntos
Transtornos Cognitivos/sangue , Lipídeos/sangue , Idoso , Estudos de Coortes , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Testes Neuropsicológicos , Características de Residência
5.
J Card Fail ; 23(1): 47-55, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27864030

RESUMO

BACKGROUND: Cognitive impairment is found in a significant proportion of patients with heart failure (HF). Although cognitive impairment may be a consequence of HF, early signs of cognitive impairment may also indicate subclinical vascular disease, and thus a risk factor for future cardiovascular events. METHODS AND RESULTS: The Atherosclerosis Risk in Communities Study is a prospective cohort study of the development of atherosclerosis. Cox proportional hazards regression was used to examine the association between mean 6-year change in cognitive function and incident HF in 7962 white and 1933 African-American men and women aged 46 to 70 years and free of clinical stroke. Scores were obtained for the Delayed Word Recall Test, the Digit Symbol Substitution Test (DSST), and the Word Fluency Test. There was a significantly increased risk of developing HF during the mean 12.6-year follow-up period after adjustment for age, gender, race, and education for those in the quartile with the greatest decline in DSST scores (hazard ratio [HR] = 1.17, P = .009), and in the quartile with the lowest baseline DSST scores (HR = 1.43, P < .001). CONCLUSIONS: The results suggest that relatively low performance on a test of information processing speed may serve as an indicator of HF risk in middle age.


Assuntos
Aterosclerose/complicações , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Insuficiência Cardíaca/epidemiologia , Características de Residência , Medição de Risco/métodos , Adulto , Idoso , Aterosclerose/epidemiologia , Disfunção Cognitiva/etiologia , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
6.
Graefes Arch Clin Exp Ophthalmol ; 255(3): 509-517, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27632216

RESUMO

PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D). METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate. RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95 % confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95 % CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors. CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.


Assuntos
Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/sangue , Lipídeos/sangue , Edema Macular/sangue , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Retinopatia Diabética/complicações , Retinopatia Diabética/etnologia , Feminino , Humanos , Incidência , Macula Lutea/patologia , Edema Macular/etnologia , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tomografia de Coerência Óptica , Estados Unidos/epidemiologia
7.
Am J Med Genet B Neuropsychiatr Genet ; 174(3): 269-282, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27781389

RESUMO

Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome-wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African-American middle-aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), Digit Symbol Substitution Test (DSST; processing speed), and Word Fluency Test (WFT; executive function). General linear models were used to assess mean differences in 6-year change in test scores among individuals categorized by genotype after adjusting for age, gender, and years of education. Addition of the minor allele for rs670139 (MS4A4E), rs9331896 (CLU), and rs12155159 (NME8) was nominally associated with change on the DWRT, DSST, and WFT, respectively, in whites. The ZCWPW1 (rs1476679) and CDS33 (rs3865444) variants were nominally associated with change on the DWRT and WFT in African-Americans. For rs670139 and rs9331896 the association was only significant in individuals bearing at least one APOE ϵ4 allele in stratified analyses. An unweighted genetic risk score aggregating the risk alleles for 15 polymorphisms was not associated with change in cognitive function. Although the AD-associated genetic variants appear to have small effects on early cognitive change, replication will be required to establish whether there is a discernible influence on cognitive status in midlife. © 2016 Wiley Periodicals, Inc.


Assuntos
Doença de Alzheimer/genética , Proteínas de Membrana/genética , Negro ou Afro-Americano/genética , Alelos , Doença de Alzheimer/complicações , Aterosclerose/complicações , Aterosclerose/genética , Aterosclerose/psicologia , População Negra/genética , Clusterina/genética , Cognição , Transtornos Cognitivos/genética , Demência/genética , Feminino , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Fatores de Risco , Tiorredoxinas/genética , População Branca/genética
8.
Retina ; 36(9): 1622-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26991647

RESUMO

PURPOSE: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. METHODS: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. RESULTS: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95% confidence interval = 1.01-1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95% confidence interval = 1.02-1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. CONCLUSION: Higher total and low-density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Exsudatos e Transudatos , Edema Macular/diagnóstico por imagem , Tomografia de Coerência Óptica , Negro ou Afro-Americano/etnologia , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etnologia , Retinopatia Diabética/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Edema Macular/sangue , Edema Macular/etnologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador
9.
J Med Virol ; 87(8): 1377-81, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25908332

RESUMO

Epidemiologic links between chronic hepatitis C and herpes simplex type-2 infection have been suggested; however, type-specific tests for HSV-2 infection have not been validated in patients with chronic hepatitis C infection. The Focus HerpeSelect(®) HSV-2 IgG (Cypress, California) assay and the Biokit HSV-2 rapid assay (Biokit USA, Lexington, MA) were performed on serum samples obtained from 84 veterans with chronic hepatitis C who demonstrated a previously positive HSV-2 serologic test in their medical records. Using the Biokit HSV-2 as the comparator assay, the positive predictive value, and specificity for the HerpeSelect(®) HSV-2 assay were 62.1% (95%CI: 49.3-73.8) and 41.9% (95%CI: 27.0-57.9), respectively. Increasing the HerpeSelect(®) HSV-2 index value defining a positive test result from >1.1 to ≥2.89 increased the assay's specificity to 97.7% (95%CI: 87.7-99.6) and the positive predictive value to 94.1%(95%CI: 71.2-99.0). J. Med. Virol. 9999: 1-5, 2015. © 2015 Wiley Periodicals, Inc. In veterans with chronic hepatitis C infection, HerpeSelect(®) HSV-2 index values between 1.1 and 2.89 should be confirmed with an alternate test for HSV-2 infection.


Assuntos
Anticorpos Antivirais/sangue , Hepatite C Crônica/complicações , Herpes Simples/diagnóstico , Herpesvirus Humano 2/imunologia , Imunoglobulina G/sangue , Testes Sorológicos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Veteranos
10.
Anesth Analg ; 121(5): 1321-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26273745

RESUMO

BACKGROUND: We conducted a retrospective chart review to determine the frequency of stridor and contributing factors after the use of Microcuff® and uncuffed tracheal tubes (TTs) in neonates. METHODS: All neonates in our neonatal intensive care unit whose airways were intubated between May 2011 and June 2012 were included. Data were collected from the neonatal intensive care unit database and from the electronic anesthesia record. Extracted data included postmenstrual age (PMA) at birth, birth weight, TT size and type, duration of tracheal intubation, and number of reintubations. The use of racemic epinephrine, heliox, and/or dexamethasone postextubation was considered diagnostic of stridor. RESULTS: Of the 324 neonates whose data were reviewed, 27 (8.3%) developed postextubation stridor. Neonates who developed stridor were more premature (PMA at birth, 29.9 ± 5.8 vs 33.0 ± 4.8 weeks, P = 0.001), had a lower birth weight (1.56 ± 1.07 vs 2.02 ± 0.96 kg, P = 0.005), greater duration of intubation (median: 20 vs 3 days, P < 0.0001), and multiple reintubations (median: 2 vs 0, P < 0.0001). The frequency of stridor was 17.2% after using Microcuff TT and 7.5% after using uncuffed TTs (Fisher exact test, 2-sided P = 0.08 [95% confidence interval for difference in proportions: -9.4% to 28.7%]). In a multivariable logistic regression model, after adjusting for PMA, birth weight, duration of intubation, and number of reintubations, the use of a Microcuff TT was associated with increased odds of stridor (adjusted odds ratio = 9.27 [95% confidence interval: 1.88-45.67], P = 0.006). CONCLUSIONS: The use of the Microcuff TT is associated with increased odds of postextubation stridor in neonates compared with the use of uncuffed TT.


Assuntos
Unidades de Terapia Intensiva Neonatal , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/estatística & dados numéricos , Sons Respiratórios/fisiopatologia , Feminino , Humanos , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Masculino , Estudos Retrospectivos
11.
Am J Epidemiol ; 179(8): 956-66, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24627572

RESUMO

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.


Assuntos
Transtornos Cognitivos/etiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Escolaridade , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Testes Neuropsicológicos , Pacientes Desistentes do Tratamento , Fatores de Risco , Fatores de Tempo
12.
Am J Physiol Regul Integr Comp Physiol ; 306(5): R328-40, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24381176

RESUMO

Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in preautonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify preautonomic neurons in the PVN. Expression of MR, GR, 11-ß hydroxysteroid dehydrogenase1 and 2 (11ß-HSD1, 2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11ß-HSD1 reductase activity was assessed by immunohistochemistry. RT-PCR and Western blot analysis were used to determine MR gene and protein expression. Most preautonomic neurons were in the caudal mediocellular region of PVN, and most expressed MR; none expressed GR. 11ß-HSD1, but not 11ß-HSD2 nor H6PD immunoreactivity, was detected in the PVN. In rats with chronic low or high sodium intakes, the low-sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-Fos immunoreactivity within labeled preautonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within preautonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, and aldosterone may be a relevant ligand for MR in preautonomic neurons of the PVN under physiological conditions. Dehydrogenase activity of 11ß-HSD1 occurs in the absence of H6PD, which regenerates NADP(+) from NADPH and may increase MR gene expression under physiological conditions.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Adaptação Fisiológica , Ração Animal , Animais , Dieta , Regulação da Expressão Gênica/fisiologia , Genes fos/genética , Genes fos/fisiologia , Imuno-Histoquímica/métodos , Neurônios/classificação , Ratos , Receptores de Glucocorticoides/genética , Receptores de Mineralocorticoides/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Hum Mol Genet ; 20(11): 2273-84, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21378095

RESUMO

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.


Assuntos
Negro ou Afro-Americano/genética , Estudo de Associação Genômica Ampla , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Pressão Sanguínea , Estudos de Coortes , Diástole , Feminino , Loci Gênicos , Genótipo , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Sístole , População Branca/genética
14.
Prostate ; 73(11): 1135-46, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23657951

RESUMO

BACKGROUND: Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory, and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is unknown. METHODS: We synthesized several natural and synthetic analogues of Res and characterized their effects on PCa cells in vitro using a cell proliferation assay. A colony formation assay and in vitro validation of luciferase (Luc) activity was done for LNCaP-Luc cells that were consequently used for in vivo studies. The efficacy of Res, trimethoxy-resveratrol (3M-Res) and piceatannol (PIC) was studied in a subcutaneous (s.c.) model of PCa using oral gavage. Tumor progression was monitored by traditional caliper and bioluminescent imaging. The levels of cytokines in serum were examined by ELISA, and the levels of compounds in serum and tumor tissues were determined by gas chromatography-mass spectrometry. RESULTS: We examined the anti-proliferative activities of Res/analogues in three PCa cell lines. We further compared the chemopreventive effects of oral Res, 3M-Res, and PIC in LNCaP-Luc-xenografts. We found that 2 weeks pretreatment with the compounds diminished cell colonization, reduced tumor volume, and decreased tumor growth in the xenografts. Both 3M-Res and PIC demonstrated higher potency in inhibiting tumor progression compared to Res. Notably, 3M-Res was the most active in inhibiting cell proliferation and suppressing colony formation, and its accumulation in both serum and tumor tissues was the highest. CONCLUSIONS: Our findings offer strong pre-clinical evidence for the utilization of dietary stilbenes, particularly 3M-Res, as novel, potent, effective chemopreventive agents in PCa.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estilbenos/administração & dosagem , Administração Oral , Animais , Linhagem Celular Tumoral , Inibidores do Crescimento/administração & dosagem , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/prevenção & controle , Resveratrol , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Stroke ; 43(5): 1218-23, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22382163

RESUMO

BACKGROUND AND PURPOSE: Unrecognized or unreported stroke-like symptoms, called covert symptoms, occur in persons free of clinical stroke. Whether covert symptoms are associated with subclinical brain infarcts (SBIs) is unknown. This study examined the association between covert stroke-like symptoms and SBI/stroke in persons with no history of stroke or transient ischemic attack. METHODS: A total of 1881 Atherosclerosis Risk in Communities (ARIC) participants free of clinical stroke or transient ischemic attack (40% male, 50% black, 47-70 years) were queried for covert symptoms and underwent cerebral MRI during the baseline MRI visit. Symptoms were reassessed after 3 years at Visit 4 (n=1001; 39% male, 50% black) and approximately 10 years with a follow-up MRI (n=1006; 40% male, 50% black, 61-83 years). RESULTS: Covert symptoms were associated with prevalent SBI (OR, 1.94; 95% CI, 1.21-3.11; P=0.006). No support was found for associations between baseline MRI symptoms and SBI at the follow up MRI visit. In participants without SBI at baseline, symptoms at Visit 4 (OR, 2.96; 1.23-7.13; P=0.016) and symptoms at the follow-up MRI visit (OR, 4.29; 2.51-7.33; P<0.001) were associated with a combined outcome of new SBI/clinical stroke on follow-up MRI. Covert symptoms at follow-up MRI visit were also associated with having new SBI (OR, 2.26; 1.18-4.32; P=0.014) on the follow-up MRI that were not seen on the baseline MRI. CONCLUSIONS: Covert neurological symptoms were associated with prevalent SBI, and when ascertained at the time of follow-up MRI, with new SBI. Covert symptoms may reflect heightened risk for infarcts.


Assuntos
Infarto Encefálico/epidemiologia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/epidemiologia , Idoso , Aterosclerose/complicações , Infarto Encefálico/patologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
16.
J Health Care Poor Underserved ; 33(1): 362-373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153226

RESUMO

PURPOSE: To understand the health needs and challenges experienced by the patient population served by a student-run free clinic in Jackson, Mississippi. METHODS: A retrospective chart review was conducted on all patients who presented between 2017 and 2019. Data collected included age, race, sex, hometown, number of visits, chief complaint, lab utilization, blood pressure, and body mass index. RESULTS: The patient population was 73.3% African American and 55.5% female and came from 88 different towns across Mississippi. Most patients (54.1%) came only once. Nearly half (46.7%) of African American patients and 50.0% of White patients were obese. The top three chief complaints were health management (40.3%), STI/UTI (9.3%), and musculoskeletal (7.5%). CONCLUSIONS: The data indicate a need for the development of programs to improve patient access to care and resources: a community health outreach program, a social health services program, and further studies to determine the effectiveness of care provided.


Assuntos
Clínica Dirigida por Estudantes , Instituições de Assistência Ambulatorial , Feminino , Humanos , Masculino , Mississippi/epidemiologia , Estudos Retrospectivos , Estudantes
17.
Am J Ophthalmol ; 233: 111-123, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166655

RESUMO

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
Prev Chronic Dis ; 8(4): A85, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21672409

RESUMO

INTRODUCTION: Obesity is one of Mississippi's pressing public health problems. Since 2005, the state has ranked first in the nation in adult obesity prevalence. For authorities to take targeted action against the obesity epidemic, counties, regions, and subpopulations that are most affected by obesity need to be identified. The objective of this study was to assess the scope, socioeconomic and geographic characteristics, and temporal trends of the obesity epidemic in Mississippi. METHODS: Using 2007-2009 Mississippi Behavioral Risk Factor Surveillance System data and auxiliary data, we applied a small-area estimation method to estimate county-level obesity prevalence in 2007 through 2009, to assess the association between obesity and socioeconomic factors and to evaluate temporal trends. We determined geographic patterns by mapping obesity prevalence. We appraised the precision of estimates by the width of 95% confidence intervals, and we validated our small-area estimates by comparing them with direct estimates. RESULTS: In 2009, the county prevalence of obesity ranged from 30.5% to 44.2%. Counties with the highest prevalence of obesity were in the Delta region and along the Mississippi River. The obesity prevalence increased from 2007 through 2009. Age, sex, race, education, and employment status were associated with obesity. CONCLUSION: The 2009 obesity prevalence in all Mississippi counties was substantially higher than the national average and differed by geography and race. Although urgent intervention measures are needed in the entire state, policies and programs giving higher priority to higher-risk areas and subpopulations identified by this study may be better strategies.


Assuntos
Sistema de Vigilância de Fator de Risco Comportamental , Obesidade/epidemiologia , Saúde Pública , Medição de Risco/métodos , Adulto , Feminino , Humanos , Masculino , Mississippi/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores Socioeconômicos
19.
Am J Perinatol ; 28(9): 689-94, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21698552

RESUMO

We describe the epidemiological characteristics and identify maternal-fetal outcomes in pregnancies complicated by gastroschisis. We retrospectively reviewed 115 cases of gastroschisis at the University of Mississippi Medical Center. The incidence of gastroschisis trended upward between 2000 and 2008. Significant proportions of mothers were nonobese, nulliparous, teenagers, smokers, and nonconsumers of alcohol. Infants delivered at > 36 weeks or without sepsis had shorter hospital stay (HS) and interval to full enteral feeding (FEF). The rates of low birth weight (LBW), fetal growth restriction, and spontaneous preterm birth (PTB) were 63%, 45%, and 24%, respectively. Bowel atresia was noted in 9%. Rates of primary closure (25%), neonatal sepsis (29%), fetal death (2%), and infant mortality (4%) were notable. Median HS and interval to FEF were 40 and 30 days, respectively. The incidence of gastroschisis is increasing in Mississippi. Sepsis, LBW, and PTB are key determinants of poor infant outcomes.


Assuntos
Peso ao Nascer , Gastrosquise/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Colo/anormalidades , Nutrição Enteral , Feminino , Retardo do Crescimento Fetal/epidemiologia , Gastrosquise/mortalidade , Gastrosquise/cirurgia , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Atresia Intestinal/epidemiologia , Tempo de Internação , Masculino , Mississippi/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , Adulto Jovem
20.
South Med J ; 104(5): 309-14, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21606706

RESUMO

OBJECTIVES: The study of noninvasive markers of fibrosis, such as aspartate aminotransferase (AST) to platelet ratio index (APRI), have been limited in African American populations. Given the disparate outcomes of chronic hepatitis C in African American populations, comparative analyses of the APRI score should be undertaken. Compare the diagnostic accuracy of the APRI score for significant fibrosis and cirrhosis in a sample of African American and white veterans with chronic hepatitis C in the southeastern United States. METHODS: We identified 268 veterans with chronic hepatitis C who had received a liver biopsy. The APRI score was calculated using laboratory values obtained within 180 days of liver biopsy and compared to the fibrosis stage (F0-F4). Performance characteristics of the APRI score for determining stages of fibrosis were compared in African American (n = 142) and white (n = 117) individuals. RESULTS: An APRI score of 0.99 had a comparably high negative predictive value for significant fibrosis (F3-F4) in African American 0.90 and white veterans (0.83). For cirrhosis (F4), an APRI score of 1.0 provided a negative predictive value of 0.96 in the African American subset and 0.94 in the white subset. We did not detect any difference in the performance of the APRI score for predicting stages of fibrosis between the two groups. CONCLUSION: The APRI score displayed similar performance in African Americans and whites. A threshold of 1.0 can reliably exclude cirrhosis in African American veterans with chronic HCV infection.


Assuntos
Aspartato Aminotransferases/sangue , Negro ou Afro-Americano/estatística & dados numéricos , Hepatite C/diagnóstico , Contagem de Plaquetas , População Branca/estatística & dados numéricos , Biópsia , Feminino , Hepatite C/sangue , Hepatite C/enzimologia , Hepatite C/patologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veteranos/estatística & dados numéricos
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