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1.
Am J Clin Nutr ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589250

RESUMO

BACKGROUND: Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. OBJECTIVES: The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. METHODS: In a subset of the CHILD cohort (n  = 1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. RESULTS: Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. CONCLUSIONS: This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

2.
Int J Soc Psychiatry ; 65(7-8): 603-614, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31387428

RESUMO

BACKGROUND: Little is known about the impacts of schizophrenia on different types of caregiving burden. AIM: This study aims to examine how the severity of schizophrenia, social functioning and aggressive behavior are associated with caregiving burden across different kinship types. METHOD: The analytic sample included 300 dyads of persons with schizophrenia and their family caregivers in Xinjin, Chengdu, China. The 10th edition of the International Classification of Diseases (ICD-10) was utilized to identify the patients, whose symptom severity, social functioning and aggressive behavior were measured. Caregiving burden was estimated using the Burden Scale for Family Caregivers-short (BSFC-s). RESULTS: A higher level of burden was significantly associated with female caregivers, larger family size, lower income, worse symptoms, poorer functional status and more aggressive behaviors. Parent caregivers showed greater burden if the patients had better functioning of social interest and concern or more aggression toward property. Mother caregivers showed greater burden than fathers. Spouses tended to perceive greater burden if the patients had better marital functioning, poorer occupational functioning or more aggressive behaviors toward property. Patients attacking others or a father with schizophrenia was related to a higher burden of child caregivers. A heavier burden of other relatives was correlated with patients' more verbal aggression and self-harm. CONCLUSION: This study shows the distinct impacts of disease-related factors on the caregiving burden across different kinship types. Our findings have implications for health-care professionals and practitioners in terms of developing more targeted family-based or individualized intervention to ameliorate burden according to kinship types and deal with behavioral and functional problems in schizophrenia.

3.
AJR Am J Roentgenol ; : 1-6, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31386572

RESUMO

OBJECTIVE. The purpose of this study was to evaluate the clinical feasibility of breath-hold (BH) MRCP with multichannel receiver coils in comparison with conventional navigator-triggered (NT) MRCP at 3 T. SUBJECTS AND METHODS. We prospectively studied 53 consecutive patients who underwent MRCP with BH sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) and NT SPACE. The acquisition time for each MRCP image was noted. The contrast ratio, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) between the common bile duct (CBD) and periductal tissues on 3D MRCP images were evaluated quantitatively. The overall image quality, motion artifacts, and CBD visibility were scored on a 4-point scale by two blinded radiologists. A paired t test was used to analyze the differences in the qualitative and quantitative evaluations between the two MRCP acquisition methods. RESULTS. Both MRCP methods were successfully performed for all subjects without any complications. The mean acquisition time of BH MRCP was significantly shorter than that of NT MRCP (18 seconds vs 264.64 ± 89.66 [SD] seconds; p < 0.001). The mean SNR, the contrast ratio, and the CNR of the CBD were significantly higher on NT MRCP images than on BH MRCP images (11.58 ± 6.24 vs 8.71 ± 4.21, 0.93 ± 0.04 vs 0.92 ± 0.03, and 15.42 ± 8.04 vs 12.00 ± 5.76, respectively; p < 0.05). All visual scores were significantly higher with BH MRCP than with conventional NT MRCP (p < 0.001). CONCLUSION. Using 3D BH MRCP with a SPACE sequence at 3 T is feasible in clinical patients, yielding significantly better perceived image quality of the pancreaticobiliary tree in a single BH (mean acquisition time, 18 seconds) without losing image quality compared with the conventional NT MRCP.

4.
Int J Infect Dis ; 86: 108-113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288091

RESUMO

OBJECTIVES: Pertussis is a highly transmissible acute respiratory infection caused by the bacterial pathogen Bordetella pertussis. The purpose of this study was to develop a rapid, simple and sensitive diagnostic test for detecting this pathogen. METHODS: Here we present a recombinase aided amplification (RAA) assay incorporating competitive internal amplification control (IAC) to detect Bordetella pertussis using the DNA obtained by boiling. This assay was performed in a single closed tube at 39°C within 30min. A total of 115 clinical samples suspected of pertussis were collected and tested by the internally controlled RAA assay using both extracted DNA with the commercial kit and the DNA obtained by boiling. For comparison, the real-time PCR (RT-PCR) was also performed with DNA extraction in parallel. RESULTS: The sensitivity of the internally controlled RAA assay was 101 copies or 10CFU/ml per reaction in detecting plasmid DNA or B. pertussis strain. The optimum concentration of the IAC plasmid was determined to be 100 copies, and the introduction of IAC effectively reduced the occurrence of false negatives. Compared to the RT-PCR, RAA results with DNA extraction obtained 100% sensitivity and specificity, and the RAA results with heat-treated DNA showed 85.96% sensitivity and 100% specificity. CONCLUSION: With the advantages of 45min turn-around time and simple steps of DNA purification, this assay could become a useful diagnostic tool for Bordetella pertussis detection and is potentially suitable for point-of-care identification to guide prompt clinical treatment.

5.
Food Funct ; 10(8): 5080-5090, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361289

RESUMO

Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1ß. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.

7.
Cell Rep ; 26(11): 3132-3144.e7, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30865899

RESUMO

Identification of human disease signature genes typically requires samples from many donors to achieve statistical significance. Here, we show that single-cell heterogeneity analysis may overcome this hurdle by significantly improving the test sensitivity. We analyzed the transcriptome of 39,905 single islets cells from 9 donors and observed distinct ß cell heterogeneity trajectories associated with obesity or type 2 diabetes (T2D). We therefore developed RePACT, a sensitive single-cell analysis algorithm to identify both common and specific signature genes for obesity and T2D. We mapped both ß-cell-specific genes and disease signature genes to the insulin regulatory network identified from a genome-wide CRISPR screen. Our integrative analysis discovered the previously unrecognized roles of the cohesin loading complex and the NuA4/Tip60 histone acetyltransferase complex in regulating insulin transcription and release. Our study demonstrated the power of combining single-cell heterogeneity analysis and functional genomics to dissect the etiology of complex diseases.

8.
J Affect Disord ; 248: 52-58, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711869

RESUMO

BACKGROUND: Many studies have shown that the disturbance of pro-inflammatory and/or anti-inflammatory cytokines is involved in the modulation of traumatic stress and related psychiatric disorders, typically posttraumatic stress disorder (PTSD). However, the specific immune alterations associated with PTSD symptoms are still unclear. The present study compared levels of pro- and anti-inflammatory cytokines between PTSD and non-PTSD controls, and investigated the relationships of immune changes with PTSD symptomatology. METHODS: In this study, 51 earthquake-exposed PTSD patients and 136 earthquake-exposed healthy controls were recruited. We assessed trauma exposure, PTSD and depression severity, and quantified a panel of pro- inflammatory cytokines, including interleukin (IL)-1ß, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), interferon ϒ (IFNϒ), and anti-inflammatory cytokines, including IL-4, IL-10 and IL-13 with enzyme-linked immunosorbent assays. Additionally, total pro-inflammatory cytokines score and total anti-inflammatory cytokines score were calculated to reflect the status of two balance system. RESULTS: Behavioral data showed that the PTSD group had greater severity of depression, as well as total symptoms and every symptom cluster in the seven-factor model of PTSD compared to the non-PTSD control group. Immune data showed that PTSD subjects had higher levels of IL-1ß and TNFα, as well as total pro-inflammatory cytokine scores compared to controls, suggesting an increase of inflammatory activity in PTSD. In all subjects, the IL-1ß levels were correlated with PCL scores, after controlling for covariates, including age, education, marital status and gender, trauma exposure severity and depression. LIMITATIONS: The current study did not include a non-traumatized healthy control group, and PTSD was assessed using a self-reported measure. CONCLUSIONS: Thus, by including a control group comprised entirely of earthquake-exposed individuals as means to discriminate specific alterations of cytokine levels in PTSD, these findings suggest that the increased inflammatory cytokines, especially IL-1ß, may play a role in the pathophysiology of PTSD.


Assuntos
Citocinas/sangue , Terremotos , Transtornos de Estresse Pós-Traumáticos/sangue , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
9.
Eur J Radiol ; 109: 13-18, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30527294

RESUMO

PURPOSE: An accurate differentiation between vestibular schwannomas (VS) and meningiomas is critical in determining treatment strategies and clinical prognoses. However, misdiagnoses may occur when typical imaging appearances are absent. The purpose of this study was to assess the performances of diffusion kurtosis imaging (DKI) and three-dimensional arterial spin labeling imaging (3D-ASL) in the differentiation of VS and meningiomas with atypical appearance. MATERIALS AND METHODS: Thirty-eight patients with pathologically proven VS and meningiomas were consecutively enrolled. All patients had no typical appearance and underwent DKI and 3D-ASL scan. Then, the DKI and 3D-ASL parameters were measured. Statistical analyses were performed using independent-sample t-tests, Mann-Whitney U tests and receiver operating characteristic (ROC) curve analyses. RESULTS: Mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), fractional anisotropy (FA) and cerebral blood flow (CBF) were significantly lower in VS than those in meningiomas, mean diffusivity (MD) were significantly higher in VS than that in meningiomas (all P < 0.05). ROC curve analyses showed that the diagnostic performance of kurtosis values outperformed those of other MR parameters. A cut-off RK value of 0.766 yielded a sensitivity of 91.67%, a specificity of 100.0%, and an accuracy of 94.74%, with an AUC of 0.988. CONCLUSION: DKI and 3D-ASL are useful for differentiating VS and meningiomas with atypical appearance, with kurtosis values of DKI have the best diagnostic efficiency.


Assuntos
Imagem de Tensor de Difusão/métodos , Imagem Tridimensional/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Neuroma Acústico/diagnóstico por imagem , Circulação Cerebrovascular , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin
10.
Respir Res ; 19(1): 248, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541564

RESUMO

BACKGROUND: Candidate gene and genome-wide association studies have identified hundreds of asthma risk loci. The majority of associated variants, however, are not known to have any biological function and are believed to represent markers rather than true causative mutations. We hypothesized that many of these associated markers are in linkage disequilibrium (LD) with the elusive causative variants. METHODS: We compiled a comprehensive list of 449 asthma-associated variants previously reported in candidate gene and genome-wide association studies. Next, we identified all sequence variants located within the 305 unique genes using whole-genome sequencing data from the 1000 Genomes Project. Then, we calculated the LD between known asthma variants and the sequence variants within each gene. LD variants identified were then annotated to determine those that are potentially deleterious and/or functional (i.e. coding or regulatory effects on the encoded transcript or protein). RESULTS: We identified 10,130 variants in LD (r2 > 0.6) with known asthma variants. Annotations of these LD variants revealed that several have potentially deleterious effects including frameshift, alternate splice site, stop-lost, and missense. Moreover, 24 of the LD variants have been reported to regulate gene expression as expression quantitative trait loci (eQTLs). CONCLUSIONS: This study is proof of concept that many of the genetic loci previously associated with complex diseases such as asthma are not causative but represent markers of disease, which are in LD with the elusive causative variants. We hereby report a number of potentially deleterious and regulatory variants that are in LD with the reported asthma loci. These reported LD variants could account for the original association signals with asthma and represent the true causative mutations at these loci.


Assuntos
Asma/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genômica/métodos , Locos de Características Quantitativas/genética , Asma/diagnóstico , Humanos , Polimorfismo de Nucleotídeo Único/genética
11.
Medicine (Baltimore) ; 97(45): e13138, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407340

RESUMO

To evaluate the accuracy of contrast-enhanced whole-heart magnetic resonance coronary angiography at 3.0T for assessing significant stenosis (≥50% lumen diameter reduction) in patients with myocardial infarction, by using conventional coronary artery angiography as the reference standard, and also test the performance of that for the detection and assessment of chronic myocardial infarction (MI), compared with standard delayed-enhancement coronary magnetic resonance (DE-CMR) for the determination of infarct size.We studied 42 consecutive patients (37 men, 5 women, mean age 58.5 ±â€Š10.7 years) with MI scheduled for conventional coronary angiography. Contrast-enhanced whole-heart coronary magnetic resonance angiography (CMRA) was employed after sublingual nitroglycerin (NTG) with the abdominal banding rolled tightly along the side of ribs. Finally, a 3D phase-sensitive inversion-recovery gradient-echo (3D-PSIR-GRE) sequence was performed during free breathing. The assessment of MI sizes on WH-CMRA reconstructed images and 3D-PSIR-GRE images were compared using a paired student t test.The acquisition of CMRA was completed in 40 (95.2%) of 42 patients, with an imaging time averaged at 9.5 ±â€Š3.1 minutes. The average navigator efficiency was 47%. The sensitivity, specificity, and positive and negative predictive values of whole-heart CMRA for the detection of significant lesions on a segment-by-segment analysis were 91.7% (95% confidence interval [CI] 83.8-96.1), 84.0% (95% CI 80.0-87.4), 57.9% (95% CI 50.0-65.8), 97.7% (95% CI 95.3-98.9), respectively, and on a patient-based analysis 93.5% (95% CI 77.2-98.9), 88.9% (95% CI 50.7-99.4), 96.7% (95% CI 80.9-99.8), and 80.0% (95% CI 44.2-96.5), respectively. Infarcts were generally higher on the CE-CMRA technique compared with the standard technique (18.0 ±â€Š7.2 cm vs 16.1 ±â€Š6.4 cm; P < .0001).Contrast-enhanced whole-heart CMRA with 3.0-T not only may permit reliable detection of significant obstructive coronary artery disease in patients with myocardial infarction, but also could identify and quantify the volume of myocardial infarction. This technique could be considered the preferred approach in patients who could not overcome longer scanning times or unable to hold their breath instead of delayed-enhancement magnetic resonance imaging for detection of infarcted myocardium. However, compared with standard imaging, the volume of myocardial infarction is slightly overestimated.


Assuntos
Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , Adulto , Idoso , Doença Crônica , Meios de Contraste , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Ecocardiografia Tridimensional/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
12.
BMC Proc ; 12(Suppl 9): 46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30275894

RESUMO

Obesity is a risk factor for heart disease, stroke, diabetes, high blood pressure, and other chronic diseases. Some drugs, including fenofibrate, are used to treat obesity or excessive weight by lowering the level of specific triglycerides. However, different groups have different drug sensitivities and, consequently, there are differences in drug effects. In this study, we assessed both genetic and nongenetic factors that influence drug responses and stratified patients into groups based on differential drug effect and sensitivity. Our methodology of investigating genetic factors and nongenetic factors is applicable to studying differential effects of other drugs, such as statins, and provides an approach to the development of personalized medicine.

13.
Pharmacogenomics J ; 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30214008

RESUMO

More than 1100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project. We identified 69,319 genetic variations within 160 pharmacogenomic genes, of which 8207 variants are in strong LD (r2>0.8) with known pharmacogenomic variants. Of the latter, eight are coding or structural variants predicted to have high impact, with 19 additional missense variants that are predicted to have moderate impact. In conclusion, we identified putatively functional variants within known pharmacogenomics loci that could account for the association signals and represent the missing causative variants underlying drug response phenotypes.

14.
Nat Commun ; 9(1): 2976, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061609

RESUMO

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

15.
Sci Rep ; 8(1): 5675, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618737

RESUMO

The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10-8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10-8) and multi-trait analysis (P = 2.9 × 10-9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes.

16.
Nat Genet ; 50(4): 524-537, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29531354

RESUMO

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

17.
Radiol Med ; 123(6): 399-405, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29426964

RESUMO

PURPOSE: The purpose of this study was to investigate the prevalence of incidental pulmonary embolism (IPE) in suspected stroke patients receiving carotid computed tomography angiography (CTA) and its characteristics. MATERIALS AND METHODS: A total of 4873 cases receiving carotid CTA between January 2013 and December 2016 were retrospectively reassessed by one radiologist. Patients with previous or suspected PE were excluded. The remaining prior contrast-enhanced carotid CTA studies were regarded as a "potentially incidental" IPE when a filling defect was found in one or more pulmonary arteries and subjected to the other two thoracic radiologists independently for reviewing and assessing for characteristics of the IPE and the image quality of the PE. The differences were noted between inpatients and outpatients in prevalence of IPE. Characteristics of the patients with IPE were also studied in terms of gender, age, as well as clinical indication. RESULTS: The prevalence of IPE among these suspected stroke patients was 0.8% on carotid CT angiography, and 24 (96%) of all IPEs had not been previously diagnosed by the original reporting radiologists. Most of the IPEs were at the lobar or segmental levels, single and in right upper lobe of pulmonary arteries. In most of the cases, the reviewing radiologists judged the contrast bolus as good. The outpatient group had a lower percentage of patients with IPE when compared with the inpatient counterpart (p = 0.024). The prevalence of IPE in patients with suspected stroke was higher with the increasing of age (p = 0.013). CONCLUSIONS: IPE can occur in suspected stroke patients on carotid CT angiography, and most of them have been previously neglected in clinical practice. Radiologists should check the higher pulmonary arterial vasculature carefully on the contrast-enhanced carotid CTA scans.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Achados Incidentais , Embolia Pulmonar/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos
18.
J Hum Genet ; 63(3): 327-337, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29321517

RESUMO

Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p < 5.0 × 10-8) for the NOX4 locus (lead variant rs2289125, ß = -0.15, p = 5.3 × 1011). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.


Assuntos
Afro-Americanos/genética , Aterosclerose/sangue , Aterosclerose/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla , Homocisteína/sangue , Adulto , Alelos , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Polimorfismo de Nucleotídeo Único , Vigilância da População , Locos de Características Quantitativas , Característica Quantitativa Herdável , Adulto Jovem
19.
Genet Epidemiol ; 42(3): 276-287, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29280188

RESUMO

Recent studies showed that population substructure (PS) can have more complex impact on rare variant tests and that similarity-based collapsing tests (e.g., SKAT) may suffer more severely by PS than burden-based tests. In this work, we evaluate the performance of SKAT coupling with principal components (PC) or variance components (VC) based PS correction methods. We consider confounding effects caused by PS including stratified populations, admixed populations, and spatially distributed nongenetic risk; we investigate which types of variants (e.g., common, less frequent, rare, or all variants) should be used to effectively control for confounding effects. We found that (i) PC-based methods can account for confounding effects in most scenarios except for admixture, although the number of sufficient PCs depends on the PS complexity and the type of variants used. (ii) PCs based on all variants (i.e., common + less frequent + rare) tend to require equal or fewer sufficient PCs and often achieve higher power than PCs based on other variant types. (iii) VC-based methods can effectively adjust for confounding in all scenarios (even for admixture), though the type of variants should be used to construct VC may vary. (iv) VC based on all variants works consistently in all scenarios, though its power may be sometimes lower than VC based on other variant types. Given that the best-performed method and which variants to use depend on the underlying unknown confounding mechanisms, a robust strategy is to perform SKAT analyses using VC-based methods based on all variants.


Assuntos
Estudos de Associação Genética , Variação Genética , Análise de Componente Principal , Simulação por Computador , Fatores de Confusão (Epidemiologia) , Humanos , Modelos Genéticos
20.
Genet Epidemiol ; 42(3): 288-302, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29226381

RESUMO

Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping. To address these challenges and to take these opportunities, we propose a robust and powerful two-step testing procedure Local Ancestry Adjusted Allelic (LAAA) association. In the first step, LAAA robustly captures associations due to allelic effect, ancestry effect, and interaction effect, allowing detection of effect heterogeneity across ancestral populations. In the second step, LAAA identifies the source of association, namely allelic, ancestry, or the combination. By jointly modeling allele, local ancestry, and ancestry-specific allelic effects, LAAA is highly powerful in capturing the presence of interaction between ancestry and allele effect. We evaluated the validity and statistical power of LAAA through simulations over a broad spectrum of scenarios. We further illustrated its usefulness by application to the Candidate Gene Association Resource (CARe) African American participants for association with hemoglobin levels. We were able to replicate independent groups' previously identified loci that would have been missed in CARe without joint testing. Moreover, the loci, for which LAAA detected potential effect heterogeneity, were replicated among African Americans from the Women's Health Initiative study. LAAA is freely available at https://yunliweb.its.unc.edu/LAAA.


Assuntos
Afro-Americanos/genética , Alelos , Grupo com Ancestrais do Continente Europeu/genética , Pool Gênico , Estudo de Associação Genômica Ampla/métodos , Simulação por Computador , Humanos , Desequilíbrio de Ligação , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estatística como Assunto , Fatores de Tempo
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