Identification of microRNAs associated with human fragile X syndrome using next-generation sequencing.

Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene which can lead to a loss or shortage of the FMR1 protein. This protein interacts with specific miRNAs and can cause a range of neurological disorders. Therefore, miRNAs could act as a novel class of biomarkers for common CNS diseases. This study aimed to test this theory by exploring the expression profiles of various miRNAs in Iranian using deep sequencing-based technologies and validating the miRNAs affecting the expression of the FMR1 gene. Blood samples were taken from 15 patients with FXS (9 males, 6 females) and 12 controls. 25 miRNAs were differentially expressed in individuals with FXS compared to controls. Levels of 9 miRNAs were found to be significantly changed (3 upregulated and 6 downregulated). In Patients, the levels of hsa-miR-532-5p, hsa-miR-652-3p and hsa-miR-4797-3p were significantly upregulated while levels of hsa-miR-191-5p, hsa-miR-181-5p, hsa-miR-26a-5p, hsa-miR-30e-5p, hsa-miR-186-5p, and hsa-miR-4797-5p exhibited significant downregulation; and these dysregulations were confirmed by RT-qPCR. This study presents among the first evidence of altered miRNA expression in blood samples from patients with FXS, which could be used for diagnostic, prognostic, and treatment purposes. Larger studies are required to confirm these preliminary results.

Recent trends in adult body mass index and prevalence of excess weight: Data from the Canadian Primary Care Sentinel Surveillance Network.

OBJECTIVE: To explore recent body mass index (BMI) trends over time among Canadian adults seen in primary care to identify the best target groups for preventive interventions. DESIGN: Retrospective descriptive cohort design. SETTING: Data for this study were derived from the Canadian Primary Care Sentinel Surveillance Network database. PARTICIPANTS: All patients aged 18 years and older who had BMI measurements available between 2011 and 2016 were identified. A closed cohort (N = 243 078 unique patients) with a start date of January 1, 2011, was defined. Patients were excluded if key variables were missing or if BMI measurements were 15 kg/m2 or less or 50 kg/m2 or greater. MAIN OUTCOME MEASURES: The dependent variable for this study was BMI (kg/m2). Measured BMI values recorded in electronic medical records were used. A linear mixed-effect estimate was fit to model changes in BMI over time with control of baseline age and sex. RESULTS: Patients in the Canadian Primary Care Sentinel Surveillance Network database experienced a modest increase in mean (95% CI) BMI by 2.1% from 28.5 (28.4 to 28.6) kg/m2 in 2011 to 29.1 (28.9 to 29.2) kg/m2 in 2016 (P < .0001). This increase is not a measured difference in BMI in the same individual but reflects the difference in the average BMI of the population in 2011 versus 2016. Male patients had BMI values that were on average 1.02 kg/m2 higher than those of female patients (P < .0001). Mean BMI values increased most rapidly in young adults (18 to 34 years) compared with older adults. CONCLUSION: The findings indicate that current obesity management in primary care is failing to moderate weight trajectories in different groups by age and sex. The results also suggest that younger age groups, in whom accelerated weight gain occurred, should be the target of prevention initiatives.

Utility of the CHA2DS2-VASc Score in Prediction of Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery.

OBJECTIVE: The authors aimed to investigate the role of CHA2DS2-VASc score and its components in prediction of postoperative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective cohort. SETTING: Single-center university-affiliated tertiary cardiac center. PARTICIPANTS: A total of 2,981 consecutive patients who underwent isolated CABG between 2010 and 2012 were included. INTERVENTIONS: All patients underwent isolated CABG and were followed until discharge or in-hospital death. The primary outcome was the development of new-onset POAF during the hospital course. MEASUREMENTS AND MAIN RESULTS: During hospitalization, continuous electrocardiogram monitoring was used to detect POAF episodes. New-onset POAF developed in 15.8% of patients following isolated CABG. Patients with POAF had significantly higher CHA2DS2-VASc scores than those without POAF (2.66 ± 1.51 v 2.12 ± 1.36, p < 0.001). After adjustment for potential confounders, CHA2DS2-VASc score was significantly associated with POAF (odds ratio [OR]: 1.295, 95% CI: 1.205-1.391). However, further analyses showed that this effect was restricted to patients with a CHA2DS2-VASc score of ≥2 (OR: 1.813, 95% CI: 1.220-2.694). In multivariate analysis of the CHA2DS2-VASc components, age ≥75 (OR: 3.737, 95% CI: 2.702-5.168), age 65 to 74 (OR: 2.126, 1.701-2.658), hypertension (OR: 1.310, 95% CI: 1.051-1.633), and cerebrovascular accident (OR: 1.807, 95% CI: 1.197-2.726) were independent predictors of POAF. However, the association between POAF and female sex, diabetes mellitus, congestive heart failure, and vascular disease was not statistically significant. CONCLUSIONS: CHA2DS2-VASc score is a useful tool for the prediction of POAF after isolated CABG. However, the risk should be interpreted cautiously, since the risk score's promising effect relies on only several of its components.

Left Atrial Size; a Missing Component in Scoring Systems for Predicting Atrial Fibrillation Following Coronary Artery Bypass Surgery.

BACKGROUND: Several risk factors have been associated with the development of postoperative atrial fibrillation (AF). However, some important factors that may play substantial roles have been neglected in the final suggested risk models. In this study, we aimed to derive a new clinical risk index to predict AF in coronary artery bypass graft (CABG) patients. METHODS: In this retrospective cohort study we enrolled 3047 isolated CABG patients. A random sample of 2032 patients was used to derive a risk index for the prediction of post-CABG AF. A multivariate logistic regression model identified the independent preoperative predictors of post-CABG AF, and a simple risk index to predict AF was constructed. This risk index was cross-validated in a validation set of 1015 patients with isolated CABG. RESULTS: Post-CABG AF occurred in 15.9% and 15.7% of the patients in the prediction and validation sets, respectively. Using multivariate stepwise analysis, four preoperative variables including advanced age, left atrial (LA) enlargement, hypertension and cerebrovascular accident contributed to the prediction model (area under the receiver operating characteristic curve curve = 0.66). The effect of advanced age appeared to be dominant [age ≥ 75 years; odds ratio: 4.134, 95% confidence interval (CI): 2.791-6.121, p < 0.001]. Moderate to severe LA enlargement had an odds ratio of 2.176 (95% CI: 1.240-3.820, p = 0.013) for developing AF in our risk index. CONCLUSIONS: LA size was an important factor in risk stratification of post-CABG AF, which remained significant in the final model. Future scoring system studies might benefit from the use of this variable to obtain a more robust predictive value.

The association between CYBA gene C242T variant and risk of metabolic syndrome.

BACKGROUND: Both inflammation and oxidative stress may contribute to pathogenesis of metabolic syndrome (MetS). The C242T polymorphism (rs4673) in the CYBA gene, as the main components of NAD (P) H oxidase, causes inter-individual variability in the enzyme activity. We aimed to investigate the association between this polymorphism with MetS and its components. METHODS: Two hundred nine patients with MetS and 232 controls were included in this study. MetS was defined based on NCEP ATP-III A criteria with some modifications. The C242T polymorphism within CYBA gene was determined by using PCR-based restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: After applying a multiple logistic regression model with adjusting for potential confounders of MetS including, age, sex, body mass index, hypertension, used medications, and diabetes mellitus, C242T polymorphism was found to be associated with the presence of MetS in men but not in the total population or in women. T allele as compared to C allele was associated with decreased odds of MetS in men (adjusted OR = 0.42, 95% CI = 0.24-0.74; P = .003), but not in women (adjusted OR = 1.03, 95% CI = 0.07-1.61; P = .890), or in the total population (adjusted OR = 0.72, 95% CI = 0.51-1.02; P = .063). CONCLUSION: This study shows that T allele of C242T polymorphism in CYBA gene is protective against MetS in Iranian men but not in women. Further cohort studies with larger sample size in subgroups of men and women are required to confirm such association in other racial or ethnic group.

Prothrombin Gene G20210A Variant in Angiographically Documented Patients with Coronary Artery Stenosis.

Background: Studies on the association between the prothrombin G20210A variant and coronary artery disease (CAD) risk are inconclusive. This study aimed to investigate the possible association between the G20210A variant in the prothrombin gene and documented CAD and its severity. Methods: This study enrolled 1460 patients who were consecutively admitted for elective coronary angiography. Via the standard angiographic techniques, coronary angiographies were done and the presence and severity of CAD were determined through the clinical vessel score and the Gensini score. Prothrombin G20210A genotypes were identified using PCR-RFLP. Results: This cross-sectional study was performed on 953 men and 507 women at a mean age of 58.21±10.33 years. The median and the interquartile range for the Gensini score were not statistically significantly different between the wild (GG) and mutant (AA+GA) genotypes (P=0.440). The association between the G20210A polymorphism and the severity of CAD with respect to the vessel score also showed no significant linear trend of higher numbers of diseased vessels (P= 0.765 for the Mantel-Haenszel test of linear trend) in the AA+GA genotype as compared with the GG genotype. Conclusion: Our data failed to confirm the hypothesis that the G20210A variant mutation may be a significant determinant of CAD risk or its severity.

Next generation sequencing applications for cardiovascular disease.

The Human Genome Project (HGP), as the primary sequencing of the human genome, lasted more than one decade to be completed using the traditional Sanger's method. At present, next-generation sequencing (NGS) technology could provide the genome sequence data in hours. NGS has also decreased the expense of sequencing; therefore, nowadays it is possible to carry out both whole-genome (WGS) and whole-exome sequencing (WES) for the variations detection in patients with rare genetic diseases as well as complex disorders such as common cardiovascular diseases (CVDs). Finding new variants may contribute to establishing a risk profile for the pathology process of diseases. Here, recent applications of NGS in cardiovascular medicine are discussed; both Mendelian disorders of the cardiovascular system and complex genetic CVDs including inherited cardiomyopathy, channelopathies, stroke, coronary artery disease (CAD) and are considered. We also state some future use of NGS in clinical practice for increasing our information about the CVDs genetics and the limitations of this new technology. Key messages Traditional Sanger's method was the mainstay for Human Genome Project (HGP); Sanger sequencing has high fidelity but is slow and costly as compared to next generation methods. Within cardiovascular medicine, NGS has been shown to be successful in identifying novel causative mutations and in the diagnosis of Mendelian diseases which are caused by a single variant in a single gene. NGS has provided the opportunity to perform parallel analysis of a great number of genes in an unbiased approach (i.e. without knowing the underlying biological mechanism) which probably contribute to advance our knowledge regarding the pathology of complex diseases such as CVD.

Association between the Hepatic Lipase Promoter Region Polymorphism (-514 C/T) and the Presence and Severity of Premature Coronary Artery Disease.

Background: Hepatic lipase (HL) plays a crucial role in lipid metabolism, but there is debate about whether HL acts in a more pro- or more anti-atherogenic fashion. We aimed to examine the relationship between the -514 C/T polymorphism within the HL gene (LIPC) and the risk of angiographically determined premature coronary artery disease (CAD). Methods: Four hundred seventy-one patients with newly diagnosed angiographically documented (≥ 50% luminal stenosis of any coronary vessel) premature CAD were compared to 503 controls (subjects with no luminal stenosis in coronary arteries). A real-time polymerase chain reaction and high-resolution melting analysis was used to distinguish between the genotypes. Results: There was no significant difference in the distribution of -514 C/T genotypes between the 2 groups in the whole population or in the men, but the examined polymorphism was found to be associated with the presence of CAD in the women (p value = 0.029). After the application of a multiple logistic regression model, the minor T allele of the LIPC gene was not found to be independently associated with the presence of CAD either in the total population (adjusted OR = 0.97, 95% CI = 0.75-1.25; p value = 0.807) or in the women (adjusted OR = 0.91, 95% CI = 0.59-1.40; p value = 0.650) and in the men (adjusted OR = 1.15, 95% CI = 0.81-1.64; p value = 0.437) separately. Conclusion: Our findings suggest that there is no relationship between the LIPC -514 C/T and the risk of premature CAD or its severity in patients undergoing coronary angiography.

Association between herpes simplex virus Types 1 and 2 with cardiac myxoma.

Most cases of atrial myxoma are sporadic, and the exact etiology is unknown. We examined if herpes simplex virus (HSV)-1 and HSV-2 antigens and/or DNA could be detected in a cohort of Iranian patients with cardiac myxomas. From July 2004 to June 2014, among a total of 36,703 patients undergoing open heart surgeries, consecutive patients with cardiac myxoma who were treated by surgical excision at our center included in this study. Of 73 patients studied, 56% were female with a mean age of 54 years (ranging from 23 to 77 years). Seventy-four myxomas were surgically removed from 73 patients, since one patient had two myxomas which were located on both the right atrium and right ventricle. The materials for this analysis were retrospectively gathered from extracted tumors that stored in a pathology bank of tissue paraffin blocks. The formalin fixed paraffin embedded tissue samples were investigated for HSV genomic DNA by both immunohistochemistry (IHC) and polymerase chain reaction (PCR) analysis. In all 74 cases there was no presence of HSV 1 and HSV 2 infection. This suggests that HSV may not play a role in sporadic cardiac myxomas; however, evidence for such association is currently lacking, and further studies are required to determine such a role.

The Role of M2000 as an Anti-inflammatory Agent in Toll-Like Receptor 2/microRNA-155 Pathway.

BACKGROUND: M2000 is a newly designed and safe Non-Steroidal Anti-Inflammatory Drug (NSAID). The aim of this study was to assess the effects of M2000 on expression levels of Suppressor of Cytokine Signaling-1 (SOCS-1) and Src Homology-2 domain-containing inositol-5'-phosphatase 1 (SHIP1) proteins via Toll-Like Receptor (TLR) 2/microRNA-155 pathway. METHODS: HEK293 TLR2 cell line and Peripheral Blood Mononuclear Cells (PBMCs) were treated by different concentrations of M2000 in MTT assay. RNA was extracted by miRNeasy Mini kit. Then, cDNA was synthesized and the expression levels of SOCS1, SHIP1 and miRNA155 were evaluated by Quantitative Real time PCR. RESULTS: Our results showed that M2000 significantly increased the expression levels of SOCS1 and SHIP-1 in Lipopolysachride (LPS)-treated and non-treated cells. Moreover, M2000 decreased expression level of miR-155 in LPS treated PBMCs. CONCLUSION: M2000 can be used as NSAID in LPS induced inflammation and decrease inflammatory cytokines production by targeting SOCS1, SHIP1 and miR-155 in auto-immune and inflammatory diseases.

NQO1 C609T Polymorphism is Associated with Coronary Artery Disease in a Gender-Dependent Manner.

Findings on the association of NQO1 C609T polymorphism in the NQO1 gene and cardiovascular disease susceptibility are controversial. The objective of the current study was to examine the relationship between this polymorphism and the presence and severity of angiographically determined coronary artery disease (CAD). One-hundred and forty-five patients with newly diagnosed angiographically documented CAD (≥50 % luminal stenosis of any coronary vessel) as case group were compared to 139 controls (subjects with no luminal stenosis at coronary arteries). The presence of C609T polymorphism was analyzed using polymerase chain reaction-based restriction fragment length polymorphism. Among total population, those with combined CT/TT (T allele carrier) genotype showed a trend toward lower odds of CAD compared to those with CC (wild type) genotype, but it did not reach a statistically significant level (p = 0.061). When data were analyzed separately for men or women, CT + TT group as compared to CC genotype was associated with decreased odds of CAD in women (adjusted OR 0.4, 95 % CI 0.2-0.9; p = 0.043), but not in men (adjusted OR 0.8, 95 % CI 0.3-1.9; p = 0.612). The C609T polymorphism within NQO1 is independently associated with CAD in women, but no association was observed in whole study population or in men.

Analyzing Gensini Score as a Semi-Continuous Outcome.

Background: Investigators frequently encounter continuous outcomes with plenty of values clumped at zero called semi-continuous outcomes. The Gensini score, one of the most widely used scoring systems for expressing coronary angiographic results, is of this type. The aim of this study was to apply two statistical approaches based on the categorization and original scale of the Gensini score to simultaneously assess the association between covariates and the presence and severity of coronary artery disease (CAD). Methods: We considered the data on 1594 individuals admitted to Tehran Heart Center with CAD symptoms from July 2004 to February 2008. The participants' baseline demographic and clinical characteristics were collected, and their coronary angiographic results were expressed through the Gensini score. The generalized ordinal threshold and two-part models were applied for the statistical analyses. Results: Totally, 320 (20.1%) individuals had a Gensini score of zero. The results of neither the two-part model nor the generalized ordinal threshold model showed a significant association between Factor V Leiden and the occurrence of CAD. However, based on the two-part model, Factor V Leiden was associated with the severity of CAD, such that the Gensini score increased by moving from a wild genotype to a heterozygote (ß = 0.44; 95% CI: 0.20-0.69 in logarithm scale) or a homozygote mutant (ß = 0.70; 95% CI: 0.28- 1.12 in logarithm scale). The proportional odds assumption was not met in our data ([Formula: see text]= 54.26; p value < 0.001); however, a trend toward severe CAD was also observed at each category of the Gensini score using the generalized ordinal threshold model. Conclusion: We conclude that besides loss of information by sorting a semi-continuous outcome, violation from the proportional odds assumption complicates the final decision, especially for clinicians. Therefore, more straightforward models such as the two-part model should receive more attention while analyzing such outcomes.

Red Cell Distribution Width and Severe Left Ventricular Dysfunction in Ischemic Heart Failure.

OBJECTIVE: The red cell distribution width (RDW), a simple and widely available marker, has been linked with an increased risk of adverse outcomes in patients with heart failure (HF) and risk of death, and cardiovascular events in those with previous myocardial infarction, but its relation with the severity of left ventricular (LV) dysfunction is not fully investigated. The aim of this study was to assess the prognostic value of the RDW in post myocardial infarction patients with typical signs and symptoms of HF and with reduced LV ejection fraction (EF). METHODS: Patients (n = 350) came from an ongoing registry of consecutive patients who admitted for ischemic heart disease at our center. All patients were followed up 1 year after the initial hospitalization by telephone interviews. The outcomes studied were mortality and hospitalization because of decompensated HF. RESULTS: RDW-coefficient of variation (express in percentage) was calculated from SD of mean corpuscular volume and mean corpuscular volume itself. Using logistic regression analysis, 3 variables consisting age, RDW level, and hemoglobin were identified as independent predictors of severe LV dysfunction (LVEF <30%). Levels of RDW were associated with the presence of severe LV dysfunction, with an accuracy of 61.4% (95% confidence interval: 56.2%-66.4%) and 66.9% (95% confidence interval: 61.8%-71.6%), using cut-off values of higher than 13.5 and 13.8, respectively. CONCLUSION: Our results suggest that elevated RDW may be used as a prognostic tool among HF patients with the documented myocardial infarction because it is an inexpensive, rapidly calculated test that is already routinely in use in practice.

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR).

BACKGROUND: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. METHODS: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. CONCLUSION: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.

Relationship between calculated total antioxidant status and atherosclerotic coronary artery disease.

OBJECTIVE: Antioxidants play a major role in the cellular protection cascade against oxidative damage. Oxidative stress has been linked to the pathogenesis of coronary atherosclerosis. Our aim was to evaluate the association between calculated serum total antioxidant status (cTAS) and the presence and severity of coronary artery disease (CAD). METHODS: One hundred and seventy-four patients with angiographically documented significant (≥50%) luminal stenosis (n=123) or with minimal (<50%) luminal stenosis (n=51) in at least one coronary artery or major branch segment in the epicardial coronary tree were categorized as CAD+ group; 88 patients with no luminal stenosis were considered as the control group. The level of cTAS (mmol/L) was evaluated using the following equation: (0.63×albumin concentration)+(1.02×uric acid concentration)+(1.53×bilirubin concentration). RESULTS: In univariate analyses, mean levels of cTAS, uric acid, and creatinine were significantly higher in CAD+ group than in controls. However, adjusted cTAS level was not found to be a CAD predictor in the total population [odds ratio (OR)=1.20; 95% confidence interval (CI): 0.81-1.76; p=0.364] or in men (OR=1.25; 95% CI: 0.73-2.12; p=0.420) and women (OR=1.20; 95% CI: 0.66-2.19; p=0.553). A weak but statistically significant correlation was found between cTAS and Gensini score (Spearman's ρ=0.16, p=0.015). CONCLUSION: In patients with suspicious CAD, the level of cTAS was not found to be an independent predictor for the presence of CAD. Further studies with larger sample size are required to confirm the results.

The rs5888 single nucleotide polymorphism in scavenger receptor class B type 1 (SCARB1) gene and the risk of premature coronary artery disease: a case-control study.

BACKGROUND: Several single nucleotide polymorphisms (SNPs) in lipid transport genes have been shown to be associated with premature coronary artery disease (PCAD). The scavenger receptor BI (SCARB1) is a key component of the reverse cholesterol transport and lipid metabolism. We aimed to examine the relationship between the rs5888 SNP within SCARB1and the risk of angiographically determined PCAD. METHODS: We used an age cut-off of 55 years for women and 45 years for men to define PCAD. Five-hundred and five patients with newly diagnosed angiographically documented PCAD (≥ 50 % luminal stenosis of any coronary vessel) as case group compared with 546 controls (subjects with no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score as well as Gensini score. A real-time polymerase chain reaction (PCR) and High Resolution Melting (HRM) analysis was used to distinguish between genotypes. RESULTS: T allele as compared to C allele was associated with increased odds of PCAD in total population (adjusted OR = 1.3, 95 % CI = 1.0 to 1.5; p = 0.020), and in women (adjusted OR = 1.3, 95 % CI = 1.0 to 1.8; p = 0.037), but not in men (adjusted OR = 1.2, 95 % CI = 0.9 to 1.5; p = 0.311). There was also no significant association between the examined polymorphism and the severity of CAD in whole or in men or women subgroups. CONCLUSIONS: Our findings suggest that the SNP (rs5888) within SCARB1 is independently associated with PCAD in a sex-dependent manner.

Cholesteryl ester transfer protein gene polymorphism (I405V) and premature coronary artery disease in an Iranian population.

The effect of human cholesteryl ester transfer protein (CETP) expression on atherogenesis is still under debate. The rs5882 (I405V) polymorphism affect CETP function. We aimed to examine the relationship between the rs5882 polymorphism and the risk of angiographically determined coronary artery disease (CAD). To define premature CAD (PCAD), an age cutoff of 55 years for women and 45 years for men was used. An age- and sex-matched case-control study was conducted in 560 patients with newly diagnosed angiographically documented PCAD (≥50% luminal stenosis of any coronary vessel) and an equal number of control patients with normal coronary arteries (no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score and Gensini score. A real-time polymerase chain reaction (PCR) and high resolution melting analysis were used to distinguish between genotypes. The I405V genotype distributions were not statistically different in CAD and non-CAD groups in univariate and multivariable-adjusted logistic regression analyzes. The median and inter-quartile range for Gensini score was not significantly different among the AA (43, 24 to 73), AG (40, 20 to 66), and GG (45, 25 to 72) genotypes (p = 0.097). Furthermore, the distribution of vessel score did not statistically differ between these genotypes (p = 0.691). Our results suggest that there is no significant association between CETP I405V polymorphism and the risk of PCAD presence and severity. Larger prospective studies are needed to investigate such associations in different populations.

Takayasu's Arteritis Presenting with Headache and Peripheral Facial Palsy: A Case Report.

Takayasu's arteritis (TA) is a rare case of granulomatous arteritis which mainly involves the aorta and its large branches. Although arterial hypertension is the most common feature of the disease in both adults and children, patients with TA may present with numerous clinical manifestations. Our patient was a 45-year-old woman, known to have hypertension from 3 years earlier following assessments made for severe headache. One year after the diagnosis of hypertension, she developed a left-sided lower motor neuron facial palsy, which was treated with oral corticosteroids (Prednisolone). Notably, the patient's headache was relieved after she took corticosteroid therapy. Transthoracic echocardiography revealed severe aortic insufficiency and aneurysmal changes in the ascending aorta, and she was referred to our center for further evaluation. In multi-slice computed-tomography angiography, significant long stenosis of the left subclavian artery was seen and the diameter of the ascending aorta was 50 mm. The patient underwent the Bentall operation. The pathologic examination of the aortic wall specimen was compatible with giant cell aortitis and more in favor of TA with the ascending aortic aneurysm. At 6months' follow-up, the patient was in good condition and had almost recovered from facial palsy.

Project Management of Randomized Clinical Trials: A Narrative Review.

CONTEXT: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. EVIDENCE ACQUISITION: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. RESULTS: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. CONCLUSIONS: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management.