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1.  Attitude of Medical and Dental First Year Students Towards Teaching Methods in a Medical College of Northern India. 
Background: Teaching in most Asian countries is still dominated by teacher-centered classrooms in which students passively receive information from the teacher. Studies have shown that students’ inactivity in traditional teacher-centered classes makes them bored that consequently decrease their concentration and learning. To counter these problems active learning methods are being promoted to enhance their interest in studying. This present study was done to explore effective teaching system from a student’s perspective. The aim of the study was to examine the attitude of medical and dental first year students towards teaching methods.
Materials and Methods: The study was undertaken at on 150 Medical and Dental first year students. The study was conducted using general questionnaires along with feedback form to know their opinion about different teaching methodology.
Results: A 94.67% of the students were unsatisfied with traditional Lecture teaching. 89.33% favoured combination of traditional lectures and active learning techniques, 74.67% students find active learning methods to be interesting, 77.33% found them as attention seekers, 89.33% are motivated for in-depth study and 85.33% students are motivated for independents learning. 100% students agreed that active learning methods provide opportunities of student interaction while 86.67% students are happy with the teacher–student interaction it provides. Audio-visual aids are the most favoured (94.67%) and test questions are most criticized active teaching method.
Conclusion: Our study disclosed that the majority of student’s positively believe in using different active learning techniques for classroom activities.
PMCID: PMC4316323  PMID: 25654017
Active learning; Dental; Medical; Passive learning; Teaching
2.  Current overview on challenges in regenerative endodontics 
Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment.
The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice.
Materials and Methods:
A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled.
Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes.
Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth.
PMCID: PMC4313471  PMID: 25657518
Endodontics; regeneration; stem cells; tissue engineering
3.  Regenerative Endodontics: A Road Less Travelled 
Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering.
PMCID: PMC4253294  PMID: 25478476
Endodontics; Regeneration; Revascularization; Scaffolds; Stem cells; Tissue engineering
4.  Reference ranges of PR duration and P-wave indices in individuals free of cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Journal of electrocardiology  2013;46(6):10.1016/j.jelectrocard.2013.05.006.
In this brief report, we provide normal reference ranges for PR duration [unadjusted and heart rate adjusted] and P-wave indices [duration, amplitude and terminal force in V1] in individuals free of cardiovascular disease and its risk factors. We used automatically processed digital ECG data from 1252 US participants [mean age 59 (± 10) years, 738 women, 588 whites, 207 African-Americans, 217 Hispanics, 240 Chinese] from the Multi-Ethnic Study of Atherosclerosis [MESA]. In multivariable adjusted linear regression models with PR and each P-wave variable as a separate outcome, significant age, sex and race differences in these markers were observed. Subsequently, we report reference ranges for abnormal [2nd and 98th percentiles], borderline abnormal [5th and 95th percentiles] and mean [SD] values of PR and P-wave indices stratified by age [middle age (45–64 years) and seniors (65–84 years)], sex [men and women] and race [whites, African Americans, Hispanics and Chinese].
PMCID: PMC3795794  PMID: 23806475
P-wave indices; PR interval; MESA
5.  Full Mouth Rehabilitation in a Medically Compromised Patient with Fluorosis 
Severely worn out dentition needs to be given definite attention as it not only affects aesthetics but can also cause psychological distress to the affected individual. It can cause chewing difficulty, temporomandibular joint problems, headaches, pain and facial collapse. Before any attempt to restore severely worn dentition, aetiology of excessive tooth wear should be established. Severe wear can result from chemical cause, mechanical cause or a combination of various causes. Dental fluorosis can also result in severe wear of teeth. Teeth sometimes become extremely porous and friable with a mottled appearance ranging from yellow to brown-black. There occurs loss of tooth substance and anatomic dental deformities resulting in un-aesthetic dentition requiring full mouth rehabilitation. Here a similar case of full mouth rehabilitation of severely worn dentition due to dental fluorosis in a 27-year-old patient is presented. This case report conjointly presents the uncommon association of diabetes insipidus with dental fluorosis. Diabetes insipidus through its characteristic symptom of polydipsia can result in intake of more than permitted dose of fluoride thus causing dental fluorosis. In literature only few cases have been reported of dental fluorosis in association of diabetes insipidus. Full mouth rehabilitation of the patient was successfully accomplished through well-planned systematic approach to simultaneously fulfill aesthetic, occlusal and functional parameters.
PMCID: PMC4149160  PMID: 25177654
Dental fluorosis; Diabetes insipidus; Rehabilitation; Tooth wear; Vertical dimension of occlusion
6.  N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis 
Circulation. Heart failure  2012;5(6):727-734.
Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population.
Methods and Results
A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54–2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3–10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001).
Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population.
Clinical Trial Registration
URL: Unique identifier: NCT00005487.
PMCID: PMC4124746  PMID: 23032197
N-terminal pro-B-type natriuretic peptide; heart failure; left ventricular mass
7.  Overview on the Current Antibiotic Containing Agents Used in Endodontics 
Antibiotics are systemically and locally used extensively in endodontics. However, local antibiotic application mode is considered more effective than systemic administration. The local mode enables the dentist to target bacteria in every nook and corner of root canal system, which is otherwise beyond reach if targeted by instrumentation or conventional root canal treatment protocols. Therefore, they are an important adjunct to conventional treatment of root canal. The present study reviews the various antibiotic containing dental agents used in endodontics. A web-based research on MedLine was performed with terms Review Articles published in the last 10 year's dental journals in English for literature researching, extracting, and synthesizing data. Relevant articles were shortlisted. Important cross-reference articles were also reviewed.
PMCID: PMC4158642  PMID: 25210667
Antibiotics; Intracanal medicaments; Irrigants; Obturation; Regeneration
8.  Minor Isolated Q Waves and Cardiovascular Events in the MESA Study 
The American journal of medicine  2013;126(5):450.e9-450.e16.
The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown.
To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA).
This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events.
During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P = .030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity.
The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.
PMCID: PMC3741651  PMID: 23582938
Electrocardiography; MESA; Minor isolated Q waves; Race/ethnicity
9.  Relations of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA) 
The British journal of nutrition  2012;109(8):1490-1497.
Type 2 diabetes is a highly prevalent but preventable disorder. We assessed the association between an a priori Mediterranean diet score (MeDiet) and fasting glucose and insulin at baseline and incident type 2 diabetes after 6-year follow-up in MESA. Dietary intake was measured at baseline by a 127-item food frequency questionnaire in 5,390 men and women aged 45-84 years free of prevalent diabetes and clinical CVD. A MeDiet score was created based on intake of 10 food components: vegetables, whole grains, nuts, legumes, fruits, ratio of monounsaturated to saturated fat, red and processed meat, dairy, fish and alcohol. Multivariable linear and proportional hazard models were used to estimate the association of MeDiet, categorized in quintiles, with baseline insulin and glucose, and incident diabetes, respectively. Models adjusted for demographic, physiologic and behavioral characteristics. After multivariable adjustment, individuals with a higher MeDiet score had lower baseline mean (95% CI) insulin levels [mean Q1: = 5.8 (5.6-6.0) umol/l; mean Q5: = 4.8 (4.6-5.0) umol/l; p-trend= <0.0001]. A higher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During follow-up, 412 incident diabetes events accrued. MeDiet was not significantly related to risk of incident diabetes (p-trend=0.64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori Mediterranean diet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and lower blood glucose prior to adjustment for obesity, but not with lower incidence of diabetes.
PMCID: PMC4002212  PMID: 22932232
10.  Psychosocial Risks: Is Risk Management Strategic Enough in Business and Policy Making? 
Safety and Health at Work  2013;4(2):87-94.
In times of continuous change and volatile markets, organizations are increasingly characterized by downsizing, work intensification, and resource rationalization. This has resulted in diversification, and the emergence of new risks within the field of occupational health and safety, with an important impact. This paper focuses on one such type of risk in the modern workplace—psychosocial risks. The current study aimed to explore stakeholder perspectives, regarding the extent to which psychosocial risks are incorporated into strategic risk management practices, at both the business and policy level.
Semi-structured interviews were conducted with 14 professionals, representing employer, expert, policy maker, and trade union stakeholder perspectives.
It was found that the majority of organizations do not sufficiently, if at all, understand and incorporate psychosocial risks into strategic decision making, whereby the key barrier related to practical difficulties of not knowing how to manage psychosocial risks adequately.
The study found that there is a need to close the gap between policy and practice on a number of levels. Future recommendations comprise a policy framework and infrastructure underpinned by educational initiatives, partnerships, and networks to drive a shift in attitudes toward recognizing the duality of the concept of risk (including both potential negative and positive outcomes) and moving beyond simple regulatory compliance.
PMCID: PMC3732138  PMID: 23961331
organizations; policy making; psychosocial risk; strategy
11.  Right Ventricular Morphology and the Onset of Dyspnea: The MESA-Right Ventricle Study 
PLoS ONE  2013;8(2):e56826.
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
PMCID: PMC3574101  PMID: 23457622
12.  Myocardial Structure, Function and Scar in Patients with Type 1 Diabetes 
Circulation  2011;124(16):1737-1746.
We report relationships of cardiovascular disease (CVD) risk factors with myocardial structure, function and scar in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
Cardiac magnetic resonance (CMR) was obtained in 1017 patients with type 1 diabetes. Gadolinium CMR was also obtained in 741 patients. The mean age was 49 ± 7 years, 52% were men, and mean diabetes duration was 28± 5 years. Associations of CVD risk factors with CMR parameters were examined using linear and logistic regression models. History of macroalbuminuria was positively associated with LV mass (by +14.8 g) leading to a significantly higher LV mass/EDV ratio (by 8%). Mean hemoglobin A1c (HbA1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 ml per unit mean HbA1c %) and stroke volume (−2.3 ml per unit mean HbA1c %) and positively related to elevated LV mass/EDV ratio (0.02 g/ml per unit). The overall prevalence of myocardial scar was 4.3% by CMR and 1.4% by clinical adjudication of myocardial infarction. Both mean HbA1c (Odds ratio (O.R.) 1.5 [1.0–2.2] per unit) and macroalbuminuria (OR 3.5 [1.2–9.9]) were significantly associated with myocardial scar as well as traditional CVD risk factors.
In addition to traditional CVD risk factors, elevated mean HbA1c and macroalbuminuria were significantly associated with alterations in LV structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function.
PMCID: PMC3215589  PMID: 21947298
Myocardial function; myocardial scar; type 1 diabetes; delayed enhancement; CMR
13.  Sex and Race Differences in Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
Circulation  2011;123(22):2542-2551.
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
PMCID: PMC3111939  PMID: 21646505
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
14.  Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
PLoS ONE  2012;7(2):e30480.
Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114).
SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex.
After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48–5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19–1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02–12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes.
SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study.
PMCID: PMC3281845  PMID: 22363441
15.  Physical Activity and Right Ventricular Structure and Function 
Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.
Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.
Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.
Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.
PMCID: PMC3056232  PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
16.  Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women 
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
PMCID: PMC3037859  PMID: 21068189
imaging; cardiovascular diseases; sex
17.  Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: The MESA-RV Study 
Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p = 0.008 and p = 0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p = 0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.
PMCID: PMC3045574  PMID: 20923324
Inflammation; thrombosis; hypertension; pulmonary
18.  The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events: Multiethnic Study of Atherosclerosis 
Background. There is an association between chronic kidney disease (CKD) and metabolic syndrome (MetS). We examined the joint association of CKD and MetS with incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African-Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and MetS was defined by NCEP criteria. Cox proportional regression adjusting for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol was performed to assess the joint association of CKD and MetS with incident CVD events. Participants were divided into four groups by presence of CKD and/or MetS and compared to the group without CKD and MetS (CKD−/MetS−). Tests for additive and multiplicative interactions between CKD and MetS and prediction of incident CVD were performed. Results. During follow-up period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression analysis demonstrated that CKD and MetS were independent predictors of CVD (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared to the CKD−/MetS− group, adjusted HR for the CKD+/MetS+ group was 5.56 (95% CI 3.72–8.12). There was no multiplicative interaction between CKD and MetS (P = 0.2); however, there was presence of additive interaction. The relative excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the attributable portion (AP) was 0.49 (0.24–0.74). Conclusion. Our findings illustrate that the combination of CKD and MetS is a strong predictor of incident clinical cardiovascular events due to presence of additive interaction between CKD and MetS.
PMCID: PMC3154776  PMID: 21860804
19.  Relation of Cardiovascular Risk Factors to Right Ventricular Structure and Function as Determined by Magnetic Resonance Imaging (Results from the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2010;106(1):110-116.
The impact of cardiovascular risk factors on the left ventricle is well known but their impact on right ventricle has not been studied using advanced imaging techniques. The purpose of this study was to determine the relation between cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images were analyzed in 4204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression models were used to study the cross sectional association between individual RV parameters and risk factors. All RV parameters except ejection fraction decreased with age (p<0.0001). RV mass was positively associated with systolic blood pressure (+0.4g, p<0.0001) and high density lipoprotein (HDL) cholesterol (+0.2g, p<0.0001); inversely with diastolic blood pressure (−0.3g, p<0.0001) and total cholesterol (−0.2g, p<0.01). RV end diastolic volume was positively associated with systolic blood pressure (+1.6ml, p<0.01) and HDL cholesterol (+1.8ml, p<0.0001); and inversely with diastolic blood pressure (−2.2 ml, p<0.0001), total cholesterol (−1.4ml, p<0.0001), current smoking (−2.7ml, p<0.05) and diabetes mellitus (−3.1ml, p<0.01). RV ejection fraction was positively related with systolic blood pressure (+1.0%, p<0.0001), HDL cholesterol (+0.4%, p<0.0001) and inversely with diastolic blood pressure (−0.7%, p<0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and HDL cholesterol are associated with subclinical changes in RV mass and volumes.
PMCID: PMC2901248  PMID: 20609657
20.  High prevalence of Left Ventricular Regional Dysfunction in Arrhythmogenic Right Ventricular Dysplasia: a tagged MRI study 
Although arrhythmogenic right ventricular dysplasia (ARVD) is characterized by predominantly right sided morphologic changes, genetic/histological and molecular changes are biventricular. Alterations in regional left ventricular (LV) strain in patients referred for suspicion of ARVD have not previously been determined.
Methods and Results
The study population included 21 patients with suspected ARVD who underwent evaluation with MRI including tagging. Eleven healthy volunteers served as controls. Global RV and LV function were studied by MRI and peak regional systolic circumferential strain (Ecc, %) was calculated by harmonic phase from tagged MRI based on a 16-segment model. Patients who met ARVD Task Force criteria were classified as definite ARVD, whereas patients with a positive family history who had one additional minor criterion and patients without a family history with at least 1 major or 2 minor criteria were classified as probable ARVD.
Of the 21 ARVD subjects, 11 had definite ARVD (63.6% males, mean age 41.2 ± 14.2 years) and, 10 had probable ARVD (30% males, 34.9 ± 12.1 years). Compared with controls (58.9 ± 6.2%), probable ARVD patients (53.6 ± 7.6%) had similar global RV ejection fraction (RVEF) (p> 0.05), but definite ARVD patients (45.2 ± 6.0%) had significantly reduced RVEF (p< 0.0001). Global LVEF was normal in all three groups (p>0.05). Compared to controls, mean LV circumferential strain (Ecc) was significantly reduced in 7/16 (44%) segments in definite ARVD, and 3/16 segments (19%) in probable ARVD (p< 0.05 for all).
There was a high prevalence of regional LV dysfunction in patients with definite ARVD, with less dysfunction in those with probable ARVD. Further, the extent of regional LV dysfunction appeared to parallel RV dysfunction, whereas global LV function was normal. Similar to the RV abnormalities, our findings suggest ARVD results in regional alterations of LV dysfunction prior to global abnormalities.
PMCID: PMC3036009  PMID: 20197508
ARVD; LV involvement; tagging; regional strain
21.  Diagnostic and Prognostic Utility of ECG for Left Ventricular Hypertrophy Defined by MRI in Relationship to Ethnicity: The Multi-Ethnic Study of Atherosclerosis (MESA) 
American heart journal  2010;159(4):652-658.
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for LV mass measurement. Ethnicity is believed to affect ECG performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity.
Methods and Results
Data were analyzed from 4967 participants (48% males, mean age 62 ± 10 years; 39% Caucasian, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 yearsfor incident CVD. Thirteen traditional ECG-LVH criteria were assessed and showed overall and ethnicity-specific low sensitivity (10–26%) and high specificity (88–99%) in diagnosing MRI-defined LVH. 10 out of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared to Caucasians (p=0.02–0.001). The sum of amplitudes of S wave in V1, S wave in V2 and R wave in V5 (a MESA specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared to prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (ROC area=0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product and Framingham-adjusted Cornell voltage predicted increased CVD risk (p<0.05).
ECG has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared to other ethnic groups.
PMCID: PMC2856691  PMID: 20362725
23.  Th2 but Not Th1 Immune Bias Results in Altered Lung Functions in a Murine Model of Pulmonary Cryptococcus neoformans Infection▿  
Infection and Immunity  2009;77(12):5389-5399.
Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known if Cryptococcus neoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C. neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show that C. neoformans can significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.
PMCID: PMC2786439  PMID: 19752036
24.  Role of cardiovascular magnetic resonance imaging in arrhythmogenic right ventricular dysplasia 
Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic cardiomyopathy characterized clinically by ventricular arrhythmias and progressive right ventricular (RV) dysfunction. The histopathologic hallmark is fibro-fatty replacement of RV myocardium. It is inherited in an autosomal pattern with variable penetrance. ARVD is unique in that it most commonly presents in young, otherwise healthy and highly athletic individuals. The cause of ARVD is not well-known but recent evidence suggests strongly that it is a disease of desmosomal dysfunction. The disease involvement is not limited only to the RV as left ventricle (LV) has also been reportedly affected. Diagnosis of ARVD is challenging and is currently based upon a multi-disciplinary work-up of the patient as defined by the Task Force. Currently, implanted cardioverter defibrillators (ICD) are routinely used to prevent sudden death in patients with ARVD. Cardiovascular MR is an important non-invasive diagnostic modality that allows both qualitative and quantitative evaluation of RV. This article reviews the genetics of ARVD, current status and role of CMR in the diagnosis of ARVD and LV involvement in ARVD.
PMCID: PMC2483704  PMID: 18570661

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