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Adenosine triphosphate-binding cassette transporter A1 (ABCA1) and hepatic lipase (LIPC) genes both play an important role in lipid metabolism. ABCA1 and LIPC gene polymorphism has been reported with conflicting results as genetic risk factor for T2DM in different populations. Due to lack of conclusive data from India, present study was conducted to assess the association of ABCA1 and LIPC gene polymorphisms with T2DM risk in the North Indian population. Two SNPs (G656A and C69T) in ABCA1 gene and one SNP (G-250A) in LIPC gene were genotyped in total of 270 subjects using PCR–RFLP genotyping method. The polymorphism at position G656A in ABCA1 and at position G-250A in LIPC gene was significantly associated with development of T2DM (p = 0.016, p = 0.001). Significant association could not be observed between C69T variant of ABCA1 gene and T2DM. Regression analysis also showed that ABCA1 variant G656A and LIPC variant G-250A are associated with T2DM risk in adjusted model for clinical/demographic variables (p = 0.000 and p = 0.034). The levels of total Chl and LDL-C were significantly higher in T2DM patients having GA + AA genotype of ABCA1 gene at SNP G656A (p = 0.012 and p = 0.021). However, BMI, HOMA-IR, TG, and insulin levels were significantly higher in T2DM patients having GA + AA genotype of LIPC gene at SNP G-250A (p = 0.011, 0.048, 0.017, 0.045 respectively). It can be concluded that A allele of ABCA1 variant G656A and LIPC variant G-250A might serve as risk factors in the development of T2DM in the North Indian population.

Ischemic heart disease is the most common cause of cardiovascular morbidity and mortality. Cardiac magnetic resonance (CMR) improves on other noninvasive modalities in detection, assessment, and prognostication of ischemic heart disease. The incorporation of CMR in clinical trials allows for smaller patient samples without the sacrifice of power needed to demonstrate clinical efficacy. CMR can accurately quantify infarct acuity, size, and complications; guide therapy; and prognosticate recovery. Timing of revascularization remains the holy grail of ischemic heart disease, and viability assessment using CMR may be the missing link needed to help reduce morbidity and mortality associated with the disease.

Coronary artery disease is thought to be responsible for up to 60%-80% of out-of-hospital cardiac arrests. The utility of Computed Tomography (CT) chest when it comes to identifying acute coronary occlusion in patients following an arrest has not been studied. We evaluated whether myocardial perfusion on a contrast-enhanced chest CT performed for a non-cardiac cause can predict culprit coronary occlusion as the cause of cardiac arrest and if the absence of a perfusion defect can exclude an ischemic etiology. A retrospective cohort of 53 consecutive patients presenting with VT or VF arrest and successful resuscitation who had contrast chest CT before angiography were identified. CT scans were reviewed for myocardial perfusion defects by a cardiologist and radiologist blinded to angiogram findings. CT results were then compared with angiograms. On coronary angiography, 22 (42%) of the patients presenting with out-of-hospital arrest had critical stenosis. Sensitivity and specificity of perfusion defect on CT in identifying critical stenosis on catheterization was 0.45, 95% CI [0.24, 0.68] and 0.77, 95% CI [59%, 90%], respectively. The positive likelihood ratio was 2.01 (0.91, 4.46) and the negative likelihood ratio was 0.70 (0.46, 1.08). The diagnostic accuracy was 64.2%. Our study did not show much utility for the use of myocardial perfusion defect on an incidental pre-angiography contrast chest CT to predict acute thrombotic occlusion in out-of-hospital cardiac arrest patients. However, this shouldn't discourage further studies evaluating the utility of contrast-enhanced CT images in predicting acute coronary occlusion.

Sodium-glucose co-transporter 2 (SGLT2) receptors are primarily located in the proximal convoluted tubule of the nephron. These receptors are responsible for almost 90% to 95% of tubular reabsorption of the glucose in the nephron. In patients with diabetes mellitus, due to upregulation of SGLT2 receptors, glucose reabsorption is further increased. The Food and Drug Administration approved SGLT2 inhibitors, such as canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin, for the treatment of type 2 diabetes. In addition to their positive effect on blood glucose, additional cardioprotective and renoprotective functions have been demonstrated in major trials such as EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI-58, and CREDENCE. Unlike other antihyperglycemic drugs, reduction in hospitalization for heart failure (HF) was also seen as a class effect with this group, mechanisms of which are probably multifactorial. Subgroup analysis from these major trials indicated a reduction in progression of nephropathy and HF readmission with SGLT2 inhibitors. Although this unique property of canagliflozin was further analyzed in the CREDENCE trial, similar trials for empagliflozin (EMPERIAL-Reduced and EMPERIAL-Preserved) and dapagliflozin (DAPA-HF) are currently underway. Recently released phase III results from DAPA-HF trial indicate that dapagliflozin shows significant reduction in death due to cardiovascular causes and hospitalization in HF compared with the placebo, in both diabetics and nondiabetics. In this review article, the authors attempt to explore the possible underlying molecular mechanisms and data from existing trials pertaining to the HF related outcomes associated with SGLT2 inhibitors.

Background Cardiac amyloidosis (CA) is diagnosed with increasing frequency in the elderly population with severe aortic stenosis (AS), especially with the low-flow, low- gradient phenotype. Prognosis is poor with no treatment. Case presentation The patient is a 94-year-old active male who presented with a stroke that fully resolved. He was found to have low-flow, low-gradient severe AS, along with concomitant CA. Gradients across the aortic valve worsened with the dobutamine challenge test. He underwent successful transfemoral aortic valve replacement (TAVR) and did well postoperatively, where he remained in the hospital for only one day. Treatment of his CA with Tafamidis was recommended; however, the patient declined due to its cost and personal preference. Conclusion To our knowledge, we report on one of the oldest patients to undergo TAVR for low-flow, low-gradient AS with concurrent CA (AS-CA). It might be prudent to screen elderly patients with AS for CA, as prognosis is worse with medical management alone. TAVR has overall improved survival in patients with AS-CA and is considered the procedure of choice, as these patients are typically older and at higher risk for surgical intervention.

Resistin (RETN) protein plays an important role in the regulation of energy, glucose, and lipid homeostasis and maintenance of fasting blood glucose level by modulating hepatic insulin action. Though RETN gene polymorphism at single nucleotide polymorphism (SNP) rs3745367 (+299 G>A) and SNP rs3745368 (+62G>A) has been indicated to be relevant to type 2 diabetes mellitus (T2D), results are contradictory due to incomplete and inconsistent studies. Meta-analysis was conducted to evaluate the relationship between RETN gene polymorphism at SNP rs3745367 and rs3745368 with risk of T2D. A present study included 5276 subjects for polymorphism for SNP rs3745367 and 3617 subjects for SNP rs3745368 reported in 16 different studies available at Pubmed, EMBASE, and Google Scholar from January 2001 to May 2018. Inclusion and exclusion criteria were followed as per international norms. Publication bias was assessed using a funnel plot. The Review Manager 5.3 software was used for statistical analysis. Polymorphism was evaluated using the odds ratio (OR) corresponding to 95% confidence interval (CI). Heterogeneity among the studies was calculated using Q test. I2 was calculated to assess the variation caused by heterogeneity. Association of RETN polymorphism and T2D was analyzed using three genetic models viz. allelic, recessive, and dominant. Significant association was observed between RETN gene polymorphism at SNP rs3745367 and T2D. The pooled odds ratio (OR) was 1.45 (95% CI 1.10–1.92) with a p value of 0.009 under an allelic genetic model, whereas no significant association was found between RETN gene polymorphism at SNP rs3745368 and T2D. The pooled OR was 1.10 (95% CI, 0.66–1.83) with a p value of 0.71 under an allelic genetic model.

Treatment of resistant hypertension is a challenge, especially in patients who have chronic kidney disease. The choice of medications may be limited in this group, making the possibility of device-based therapies attractive. We explore 4 devices and procedures available to treat this vexing issue.

Background and aim INPPL1 gene encodes a lipid phosphatase Src homology 2-containing 5′-inositol phosphatase 2 (SHIP2) which is involved in the negative regulation of insulin signaling. In the light of several association studies of INPPL1 gene polymorphisms with T2DM, and the absence of association studies from India, present study was conducted to assess the association of two SNPs of INPPL1 gene with T2DM risk in North Indian population. Material and method Two single nucleotide polymorphism (SNPs) (+1893CC/AA and + 2945AA/GG) in INPPL1 gene were genotyped in total of 270 subjects with PCR-RFLP genotyping method. Results It was observed that, out of the two SNPs, only +1893CC/AA was found to be significantly associated with T2DM and frequency of A allele (C vs A, p = 0.002) has been found to be significantly higher in T2DM cases. Strong linkage disequilibrium was observed between two SNPs as assessed through D′ and r2 (D′ = 0.984, r2 = 0.009) and AG haplotype (OR = 3.59, 95% CI (1.59–9.80), p = 0.0015) was associated with increased risk of T2DM while CG haplotype (OR = 0.54, 95% CI (0.33–0.88) p = 0.012) significantly decreases the risk of developing T2DM. Regression analysis showed that SNP +1893CC/AA is associated with T2DM risk when adjusted for clinical/demographic variables. Conclusion Results showed that INPPL1 gene polymorphism +1893CC/AA may increase susceptibility to T2DM and ‘A' allele might be serving as a risk factor in development of T2DM in Indian population.

Ranolazine is a piperazine derivative approved as an antianginal. Primarily used as a second-line antianginal in stable coronary artery disease. Ranolazine blocks the late Na + current and prevents the rise of cytosolic calcium. It decreases myocardial wall tension and improves coronary blood flow. Ranolazine is effective in atrial fibrillation (AF) as an adjunct to electrical or pharmacological cardioversion. It can be used in combination with amiodarone or dronedarone. It has also been used in AF arising after coronary artery bypass grafting surgery. Role of ranolazine is also being evaluated in pulmonary arterial hypertension, diastolic dysfunction, and chemotherapy-induced cardiotoxicity. Ranolazine has some anti-glycemic effect and has shown a reduction of hemoglobin A1c in multiple trials. The antianginal effect of ranolazine has also been seen to be more in patients with diabetes compared to those without diabetes. Ranolazine is being evaluated in patients with the peripheral arterial disease with intermittent claudication and hypertrophic cardiomyopathy. Pilot studies have shown that ranolazine may be beneficial in neurological conditions with myotonia. The evidence-base on the use of ranolazine in various conditions is rapidly increasing with results of further trials eagerly awaited. Accumulating evidence may see ranolazine in routine clinical use for many conditions beyond its traditional role as an antianginal.

Inflammatory Cardiomyopathies, with overlapping features on cardiac MRI, could be a fertile ground for diagnostic pit falls A 55 year old female with palpitations manifested inferolateral T wave inversions on EKG. Left ventricular function was normal on echocardiography. A 30 day monitor showed

Inhibitors of sodium-glucose cotransporters type-2 are the most recent addition to the armamentarium of oral antidiabetic agents. This class of drugs has shown promising results in glycemic control and most importantly to reduce cardiovascular disease (CVD) mortality risk. Despite the encouraging data, there is concern regarding their potential for causing or worsening peripheral artery disease (PAD), which may increase the risk of lower extremity amputations. Following the publication of results of CANVAS and CANVAS-R trials, which revealed that leg and mid-foot amputations occurred about twice as often in patients treated with canagliflozin compared to placebo, the Food and Drug Administration (FDA) in the United States issued a black box warning of leg and foot amputations associated with canagliflozin use. In this article, our main aim is to review the available evidence in preclinical and clinical studies regarding SGLT-2 inhibitors and PAD events, the possible mechanisms related to increased risk of amputation, to evaluate whether it is a class effect or individual drug effect, and most importantly, implications for their continued use as antidiabetic agents. It also raises the issue of including PAD events among the end-points when assessing future antihyperglycemic agents. Thus, we also tried to analyze whether outcomes of SGLT2 inhibitors trials mostly focused on stroke, myocardial infarction, heart failure, and peripheral vascular disease-related outcomes remained underrated.

MRI provides a non-invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T1, T2 and T2*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T1, T2 and T2* maps, we posited that an integrated treadmill exercise-quantitative relaxometry paradigm can rapidly characterize exercise-induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T1, T2 and T2* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post-exercise. Our results show that T1, T2 and T2* are significantly and differentially increased immediately post-exercise among the leg muscle groups, and these values recover to near baseline within 30-44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender.

Diabetic cardiomyopathy is recognized as a distinct disease entity characterized by left ventricular dysfunction in absence of hypertension or coronary artery disease, and independent of glucose control. Early detection may be particularly important for preventing cardiovascular morbidity and mortality, but prospective evidence for this approach is lacking. The pathophysiology of diabetic cardiomyopathy does not remain completely understood. Besides several animal models, contemporary imaging techniques have helped not only to define this clinical entity, but to also understand pathophysiologic mechanisms. This review aims to highlight the current understanding of the disease process and to discuss current imaging methods and their limitations.

ObjectivesThis study assessed whether the results of major, potentially practice-altering cardiovascular trials were influenced by the authors' self-declared financial conflicts of interest (FCOI). Secondary objectives included assessment of trial outcomes by source of funding, by FCOI subtype, and by trial endpoints.BackgroundFinancial conflicts of interest, ubiquitous in cardiovascular medicine because of significant investigator-industry collaborations, potentially can influence trial outcomes.MethodsA MEDLINE search was performed using the MeSH term cardiovascular disease limited to randomized controlled trials and clinical trials published from January 1, 2000, through April 15, 2008, in 3 high-impact journals. Two reviewers independently abstracted data from the published article. Chi-square tests, Fisher exact tests, and multivariate logistic regression were used to assess the associations between FCOI and study characteristics and between FCOI and trial outcomes.ResultsOf the 550 articles reviewed, 51.1% satisfied FCOI criteria, including at least one of the following: stock ownership, employee, speaker's bureau, and consultant). Of the 538 articles providing sponsorship information, 34.6% reported funding solely by nonprofit organizations, 48.3% reported funding solely by industry, and 17.1% reported funding by a combination. Prevalence of FCOI significantly increased with level of industry funding: 21.5% (none), 50.0% (shared), 75.0% (industry solely, n = 281, p < 0.0001). However, no differences in reporting of favorable results were detected when articles were analyzed by self-declared FCOI (60.5% vs. 59.5% in those with and without, odds ratio: 1.04, p = 0.81). This result was upheld in multivariate analysis.ConclusionsAuthors' self-declared FCOI and source of funding do not seem to impact outcomes in major cardiovascular clinical trials.

Current models incompletely risk-stratify patients with acute chest pain. In this study, N-terminal pro-B-type natriuretic peptide and cystatin C were incorporated into a contemporary chest pain triage algorithm in a clinically stratified population to improve acute coronary syndrome discrimination. Adult patients with chest pain presenting without myocardial infarction (n = 382) were prospectively enrolled from 2008 to 2009. After clinical risk stratification, N-terminal pro-B-type natriuretic peptide and cystatin C were measured and standard care was performed. The primary end point was the result of a clinical stress test. The secondary end point was any major adverse cardiac event at 6 months. Associations were determined through multivariate stratified analyses. In the low-risk group, 76 of 78 patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 97%). Normal biomarkers predicted normal stress test results with an odds ratio of 10.56 (p = 0.006). In contrast, 26 of 33 intermediate-risk patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 79%). Biomarkers and stress test results were not associated in the intermediate-risk group (odds ratio 2.48, p = 0.09). There were 42 major adverse cardiac events in the overall cohort. No major adverse cardiac events occurred at 6 months in the low-risk subgroup that underwent stress testing. In conclusion, N-terminal pro-B-type natriuretic peptide and cystatin C levels predict the results of stress tests in low-risk patients with chest pain but should not be substituted for stress testing in intermediate-risk patients. There is potential for their use in the early discharge of low-risk patients after clinical risk stratification.

Background Few published data are available on the benefits of aspirin use in patients with unstable angina (UA). Hypothesis Aspirin use carries a mortality benefit in a population-based cohort of patients presenting with UA. Methods All residents of Olmsted County, Minnesota presenting to local emergency departments with acute chest pain from January 1985 through December 1992 having symptoms consistent with UA were identified through medical records. A total of 1628 patients were identified with UA and were stratified by aspirin use in-hospital and at discharge. Cardiovascular mortality and nonfatal myocardial infarction and stroke were assessed over a median of 7.5 years follow-up and all-cause mortality data over a median of 16.7 years. The mean age of patients with UA was 65 years, and 60% were men. Results After a median of 7.5 years follow-up, all-cause and cardiovascular-mortality rates were lower among patients prescribed versus not prescribed aspirin on discharge. There were 949 postdischarge deaths over the median follow-up of 16.7 years. After multivariable adjustment, aspirin use at discharge was associated with a lower long-term mortality (hazard ratio 0.78; 95% confidence interval, 0.65–0.93). Conclusions Aspirin use at hospital discharge following UA is associated with a reduction in long-term mortality. This long-term study extends prior trial results from select populations to a population-based cohort. Copyright © 2010 Wiley Periodicals, Inc. This study was made possible by the Rochester Epidemiology Project (grant no. R01-AR30582 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases). The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Functional coronary ischemia testing is frequently utilized to stratify unstable angina (UA) in emergency department, which is time and resource consuming. We propose that an efficient biomarker based approach including N-terminal pro b-type natriuretic peptide (NT-pro BNP) could supplement

Stress testing to identify obstructive coronary artery disease (CAD) in chest pain (CP) is time-consuming and expensive. We propose a biomarker based approach including N-terminal pro-B-natriuretic peptide (NT-pro BNP) to complement stress testing. ROBUST (Role of Biomarkers in Unstable Angina) was

The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years.The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk.In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy.

Few data are available on the association of high-sensitivity C-reactive protein (hs-CRP) and mortality independent of low-density lipoprotein (LDL) cholesterol in patients undergoing percutaneous coronary intervention (PCI).Consecutive patients (N = 8,834) undergoing PCI between October 28, 2002, and December 31, 2006, were followed through June 30, 2007 (average and maximum follow-up of 1.9 and 4.6 years, respectively). High-sensitivity CRP levels were classified into 4 groups:1.0, 1.0 to 2.9, 3.0 to 9.9, andor =10 mg/L.All-cause mortality rates were 14.4, 17.5, 25.7, and 56.4 per 1,000 person-years in patients with hs-CRP levels of1.0, 1.0 to 2.9, 3.0 to 9.9, andor =10 mg/L, respectively. Compared with patients with hs-CRP1.0 mg/L, the hazard ratios of mortality after multivariable adjustment, including LDL cholesterol, associated with hs-CRP levels of 1.0 to 2.9, 3.0 to 9.9, andor =10 mg/L were 1.27 (95% CI 0.91-1.75), 1.70 (95% CI 1.26-2.29), and 2.99 (95% CI 2.24-3.99), respectively (P trend.001). After multivariable adjustment, trends of higher all-cause mortality at higher hs-CRP were present for patients with LDL cholesterol70, 70 to 99, andor =100 mg/dL (each P.001). A test for interaction between LDL cholesterol and hs-CRP on all-cause mortality was not significant (P = .30).High-sensitivity CRP levels provide significant incremental prognostic information for all-cause mortality in long-term follow-up independent of LDL cholesterol.

The objective of this study was to determine short- and long-term cardiovascular outcomes in unselected patients with diabetes mellitus (DM) with acute ischemic chest pain (AICP). In patients with DM presenting to the emergency department with AICP, short-term cardiovascular outcomes remain discordant between trials and registries, whereas long-term outcomes are not well-described. A consecutive cohort of all residents of Olmsted County, Minnesota, presenting with AICP from January 1, 1985, to December 31, 1992, was followed for a median duration of 16.6 years. The primary outcome was long-term all-cause mortality. Other outcomes included a composite of death, myocardial infarction, stroke, and revascularization (major adverse cardiovascular and cerebrovascular events [MACCEs]) as well as heart failure (HF) events at 30 days and at a median of 7.3 years, respectively. Of the 2,271 eligible patients, 336 (14.8%) were classified with DM. The crude 30-day MACCE rate was 10.1% in patients with DM and 6.1% in those without DM (p = 0.007). HF events were more common in patients with DM at 30 days (9.8% vs 3.1%, p

Diabetic cardiomyopathy is the presence of myocardial dysfunction in the absence of coronary artery disease and hypertension. Hyperglycemia seems to be central to the pathogenesis of diabetic cardiomyopathy and to trigger a series of maladaptive stimuli that result in myocardial fibrosis and collagen deposition. These processes are thought to be responsible for altered myocardial relaxation characteristics and manifest as diastolic dysfunction on imaging. Sophisticated imaging technologies also have permitted the detection of subtle systolic dysfunction in the diabetic myocardium. In the early stages, these changes appear reversible with tight metabolic control, but as the pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients independently of common comorbidities, such as coronary artery disease and hypertension. Therapeutic agents specifically targeting processes that lead to these pathophysiologic changes are in the early stages of development. Although glycemic control and early administration of neurohormonal antagonists remain the cornerstones of therapeutic approaches, newer treatment targets are currently being explored.

The non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are commonly utilized agents for musculoskeletal conditions. The harmful cardiorenal effects of some nsNSAIDs are well described and thought to be related to inhibition of prostanoid synthesis. Since the non-specific inhibition of both cyclooxygenase enzymes was associated with a higher incidence of gastrointestinal side effects, the selective targeting of the COX-2 enzymes with the COX-2 inhibitors promised and delivered a lower incidence of gastrointestinal side effects. However, the COX-2 inhibitors have not been found to be bereft of cardiorenal side effects. Indeed, some of these agents lead to increased blood pressure, an excessive risk of congestive heart failure and pro-thrombotic effects, especially in high risk populations. These deletrious effects, however, may not be class-specific and possibly related to pharmacokinetics, enzyme specificity and endothelium effects. This article also reviews the body of literature linking the nsNSAIDs and COX-2 inhibitors with important adverse cardiorenal effects and their putative mechanisms.

The effect of the variables of polydimethylsiloxane (PDMS) soft segment (SS) length, hard segment (HS) type and content as well as choice of chain extender (its MW and symmetry) on the morphology of segmented polyurethane and polyurea copolymers was investigated. The methods of dynamic mechanic analysis, small angle X-ray scattering, atomic force microscopy, and mechanical testing were used in this analysis. Average PDMS MW of 900, 2500 or 7000 g/mol were utilized and the hard segment content ranged from 16 to 50 wt%. HMDI was used as the diisocyanate. All copolymers were synthesized via the prepolymer method. The PDMS MW had a marked effect on the morphology of the materials. Copolymers with PDMS MW of 2500 and 7000 g/mol were clearly found to be well microphase separated relative to those containing the 900 g/mol PDMS SS. The polyurea sample with a PDMS MW of 7000 and HS content of 25 wt% exhibited a remarkable service temperature window (for rubber-like behavior) of ca. 230 °C (from −55 to 175 °C) whereas it was ca. 200 °C wide (from −55 to 145 °C) for the equivalent polyurethane sample. In general, the degree of microphase separation was found to be greater in the polyurea samples due to their more cohesive bidentate hydrogen bonding.

Objectives: To assess the effect of sliding scale insulin (SSI) use on glycemic control and length of hospital stay in patients with diabetes mellitus. Methods: A prospective cohort study of 182 patients with diabetes mellitus as a primary diagnosis or a comorbid condition admitted consecutively to the internal medicine wards over a 6-week period. Demographic, clinical and laboratory data were collected from in-patient medical records. Data were analyzed using Chi-square and independent t-tests and presented as the mean ± standard error of the mean. Results: Of the total 182 in-patients with Type 2 diabetes, 130 (71.4%) were placed on SSI (Group A) and 52 (28.6%) on standing-dose antihyperglycemic therapy without the use of SSI (Group B). While there was no difference in admission blood glucose values (mg/dl) between Group A (236 ± 14.3) and Group B (237 ± 6.4), higher average in-hospital fasting blood glucose values were recorded from Group A (168 ± 7.2) compared with Group B (139 ± 11.5), p = 0.04. Plasma glucose values at discharge were not significantly different between the two groups with an average of 172 ± 8.1 for Group A and 170 ± 18.1 for Group B. Also, there was no significant difference in the number of days of hospitalization between the two groups with an average of (7.6 ± 0.89) for Group A and (10 ± 4.7) for Group B. Conclusion: SSI use is associated with higher in-hospital blood glucose and does not offer any advantage in terms of duration of hospital stay as compared with standard-dose antihyperglycemic therapy.

The influence of the extent of hydrogen bonding in mediating the long-range connectivity and percolation of the hard segment phase in model tri-segment oligomeric polyurethanes (PU) was explored by using LiCl as a molecular probe. A 22 wt% hard segment containing model PU plaque based on a mono-functional oligomeric polyether, 80:20 2,4:2,6 isomeric mixture of toluene diisocyanate, and water as a chain extender was employed. Samples cast from 20 wt% solutions in dimethyl acetamide were utilized. The tapping-mode atomic force microscopy (AFM) phase image of the solution cast film sample (soft segment Tg −63 °C) without LiCl exhibited the presence of long interconnected ribbon-like hard domains. The long-range connectivity and percolation of the hard phase that arose during plaque formation gave rise to a brittle rigid solid. A systematic break-up of the hard domains was also observed by AFM when the concentration of LiCl was increased from 0.1 to 1.5 wt%. DSC analysis indicated that the samples were able, however, to maintain a microphase separated morphology even at the highest LiCl concentration utilized in the study. FT-IR data confirmed that LiCl interacts with the hard domains of the model PU samples by disrupting the hydrogen bonding capability of the urea hard segments. A systematic softening of the samples was observed with increasing LiCl content as confirmed by thermomechanical analysis. Thus, this study indicates that hydrogen bonding plays an important role in assisting the hard segments in PU to develop long-range connectivity and percolation of this phase through the soft matrix.

Low molecular weight model trisegmented polyurethanes based on monofunctional polyols, or ‘monols’, with water-extended toluene diisocyanate (TDI) based hard segments (HS) are investigated. The formulations of the materials generated are similar to those of flexible polyurethane foams with the exceptions that the conventional polyol is substituted by an oligomeric monofunctional polyether of ca. 1000 g/mol molecular weight; and no surfactant is utilized. Plaques formed from these model systems are shown to be solid materials at ambient even at their relatively low molecular weights of 3000 g/mol and less. SAXS, DSC, and AFM are utilized to investigate the microphase separated morphologies of the samples generated. WAXS results show that the local packing of the HS is of a similar nature as that in actual flexible polyurethane foams. AFM phase images, for the first time, reveal the ability of the HS to self-assemble through bidentate hydrogen bonding and form lath-like percolated structures, resulting in solid plaques, even though the overall volume of the system is well dominated by the two terminal liquid-like polyether segments.

Approximately 30 years after their preparation, the nanoscale morphology of a series of ‘model’ segmented polyurethane elastomers has been further elucidated using the technique of tapping mode AFM. The materials investigated are based on 1,4-butanediol extended piperazine based hard segments and employ poly(tetramethylene oxide) soft segments. The chemistry of these polyurethanes was specifically controlled in a manner which yielded monodisperse hard segments precisely containing either one, two, three, or four repeating units. Phase images obtained via AFM, for the first time, enable visual representation of the microphase separated morphology of these materials. AFM images also confirmed the presence of a spherulitic morphology, as shown several years ago using SALS and SEM. In addition, applying AFM to films of freshly prepared solution cast samples, the observed lath-like hard domains are suggested to preferentially orient with their long axis along the radial direction of the spherulites, while the respective crystalline hard segments comprising the hard domains are, in turn, preferentially oriented perpendicular to the spherulitic radius. The hard domain connectivity was found to increase with increasing percentage hard segment content of the polymers.

The cardiometabolic syndrome, an interesting constellation of maladaptive cardiovascular, renal, metabolic, prothrombotic, and inflammatory abnormalities, is now recognized as a disease entity by the American Society of Endocrinology, National Cholesterol Education Program, and World Health Organization, among others. These cardiovascular and metabolic derangements individually and interdependently lead to a substantial increase in cardiovascular disease (CVD) morbidity and mortality, making the cardiometabolic syndrome an established and strong risk factor for premature and severe CVD and stroke. Established and evolving treatment strategies including moderate physical activity, weight reduction, rigorous blood pressure control, correction of dyslipidemia, and glycemic control have proven beneficial in reversing these abnormal responses and decreasing the CVD risk.

Lithium bromide (LiBr) was incorporated in formulations based on molded flexible polyurethane foams in order to alter systematically the phase separation behavior and thus give insight into urea phase connectivity. The formulations of the materials generated were similar to those of molded flexible polyurethane foams except that a surfactant and a low molecular weight cross-linking agent (such as diethanol amine) were not used. The resulting materials were evaluated by using the techniques of atomic force microscopy (AFM), SAXS, and DSC. Atomic force microscopy and SAXS were used to demonstrate that the materials with and without LiBr were microphase separated and possessed average interdomain spacings of ca. 90 A, typical of flexible polyurethane foams. AFM phase images also showed that incorporation of LiBr reduced the urea phase aggregation, which is known to take place in flexible polyurethane foams, and led to a more homogeneous distribution of the urea microdomains in the soft polyol phase....

In continuing efforts to understand urea phase connectivity in flexible polyurethane foams and its implications on physical properties, LiCl is used to alter the phase-separation behavior of slabstock foams. Comparisons are also drawn with plaque counterparts, which are prepared using the same polyol, isocyanate, and chain extender (water). LiCl is shown to alter the solid-state phase separation behavior of the foams and the plaques in a similar manner. This is confirmed using multiple characterization techniques, which provide information at different scale lengths. The foams and plaques with and without LiCl are shown to possess a microphase separated morphology with interdomain spacings of ca. 100 A. SAXS and TEM reveal that addition of LiCl reduces the urea aggregation behavior, typical in slabstock polyurethane foams, leading to a loss in the urea phase macro connectivity. Hard segment ordering, as studied by WAXS and FTIR, is shown to be of a similar nature in the plaque and foam, which do not incorporate LiCl. Addition of LiCl leads to a loss in the segmental packing behavior, or micro level connectivity of the urea phase, in both the plaques and corresponding foams, as inferred from WAXS and FTIR. The LiCl additive interacts with the polyol soft segments in an insignificant manner as shown from FTIR and DMA. In addition, foams containing LiCl are found to possess more intact cell windows due to the influence of LiCl on reaction kinetics as well as its effect on the precipitation of the urea phase. The experimental observations are supported by quantum mechanical calculations using a density functional theory approach, where molecular interactions between LiCl and model ether, urethane, and urea compounds are investigated. Interaction geometries of most stable complexes and their stability energies are calculated. Stability energies of ether/LiCl, urethane/LiCl, and urea/LiCl were determined to be −189, −617, and −687 kJ/mol, respectively, reinforcing that LiCl interacts predominantly with urea hard segments and in a minimal manner with the polyol soft segments.

The left ventricle (LV) typically dominates the conversation around cardiovascular risk. This includes symptoms stemming from LV ischemia, signs of increased LV voltage by electrocardiography in hypertensive heart disease and, apparently, a focus on the LV to open an editorial devoted to the right ventricle (RV) in preclinical risk assessment.

The morphological features of three flexible slabstock polyurethane foams based on varied contents of 2,4 and 2,6 toluene diisocyanate (TDI) isomers are investigated. The three commercially available TDI mixtures, that is, 65:35 2,4/2,6 TDI, 80:20 2,4/2,6 TDI, and 100:0 2,4/2,6 TDI were used. The foams were characterized at different length scales with several techniques. Differences in the cellular structure of the foams were noted with scanning electron microscopy. Small-angle X-ray scattering was used to demonstrate that all three foams were microphase-separated and possessed similar interdomain spacings. Transmission electron microscopy revealed that the aggregation of the urea phase into large urea-rich regions decreased systematically on increasing the asymmetric TDI isomer content. Fourier transform infrared spectroscopy showed that the level of bidentate hydrogen bonding of the hard segments increased with the 2,6 TDI isomer content. Differential scanning calorimetry and dynamic mechanical analysis (DMA) were used to note changes in the soft-segment glass-transition temperature of the foams on varying the diisocyanate ratios and suggested that the perfection of microphase separation was enhanced on increasing the 2,6 TDI isomer content. The preceding observations were used to explain why the foam containing the highest content of the symmetric 2,6 TDI isomer exhibited the highest rubbery storage modulus, as measured by DMA. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 258–268, 2003

Urea phase connectivity has been probed by systematically varying the hard segment content, and lithium chloride content, in a series of plaques based on slabstock flexible polyurethane foams. The plaque formulations are identical to those of slabstock polyurethane foams with the exception that a surfactant is not utilized. Small angle X-ray scattering (SAXS) is used to demonstrate that all materials investigated are microphase separated with similar interdomain spacings, irrespective of hard segment content (21–37 wt%) or LiCl content. Several complimentary characterization techniques are employed to reveal that urea phase connectivity is present at different length scales. Macrolevel connectivity, or connectivity of the large-scale urea rich aggregates typically observed in flexible slabstock polyurethane foams, is probed using SAXS, TEM, and atomic force microscopy. These techniques collectively show that the urea aggregation increases as the hard segment content is increased. Incorporation of LiCl is shown to systematically reduce the urea aggregation behavior, thus leading to a loss in the macroconnectivity of the urea phase. Wide angle X-ray scattering is used to probe the regularity in segmental packing, or the microlevel connectivity between the hard segments, which is observed to decrease systematically on addition of LiCl. The loss in microlevel connectivity is suggested to increase chain slippage, and leads to increased rates of stress-relaxation for the samples containing LiCl. Materials containing LiCl also display relatively short rubbery plateaus as compared to their counterparts which do not contain the additive. Modulus values, as obtained at ambient conditions by stress-strain analyses, are found to be a stronger function of LiCl content when the hard segment content is higher.

Lithium chloride was added to systematically alter the phase separation behavior, and hence, the nature of urea phase connectivity, in a series of plaques based on molded flexible polyurethane foam formulations. The plaques prepared were found to possess varied levels of urea phase connectivity that was examined at different length scales using several characterization techniques. SAXS, TEM, and t-AFM were used to show that addition of LiCl systematically reduced the formation of the urea aggregate structures typically observed in flexible polyurethane foam formulations and thus led to a loss in urea phase connectivity at the macrolevel. SAXS, DSC, and DMA revealed that formulations with and without LiCl exhibited similar interdomain spacings and soft segment glass transitions, suggesting that incorporation of LiCl did not prevent the plaques from undergoing partial microphase separation. WAXS demonstrated that addition of LiCl led to a loss in the local ordering of the hard segments within the microdomains, i.e., it led to a reduction of microlevel connectivity or the regularity in segmental packing of the urea phase. High-magnification t-AFM images showed that increasing the LiCl content dispersed the urea component more homogeneously and in a more uniform manner in the polyol matrix, and thus altered the connectivity of the urea phase at the microdomain level. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2956–2967, 2002

Introduction: Late gadolinium enhancement on cardiac magnetic resonance imaging (LGE-CMR) has been shown to predict adverse cardiovascular outcomes, especially ventricular arrhythmic events. Hypothesis: A few studies, limited by small sample size, have examined the relationship between myocardial scar and cardiac resynchronization therapy (CRT) response. We performed a meta-analysis to determine whether scar identified on LGE predicts response to CRT in cardiomyopathy. Methods: We searched PubMed and Embase for clinical trials reporting CRT response based on scar determined by LGE -CMR. Primary outcome was defined as improvement in NYHA class or echocardiographic parameters (not limited to but including dP/dT, radial strain and reduction of LV end systolic volume). Random effects model was used to pool the data across the studies. Results: After screening 1876 articles, we identified 14 clinical trials that met inclusion criteria. A total of 984 patients were included in the analysis. There was no significant heterogeneity across the studies (I 2 =30%, p= 0.13). Presence of scar on LGE-CMR decreased CRT response by 39% (RR: 0.61 (95% CI 0.53 - 0.71; p Conclusions: The presence of any myocardial scar detected by LGE predicts sub-optimal response to CRT in cardiomyopathy. This shows that identification of scar using LGE- CMR can be used as an important risk stratification tool for CRT response.

Weeds, one of the major kinds of pests, continue to cause major problems in agriculture throughout the world, reducing yield and quality of crops by competing for water, nutrients, and sunlight, essential for vigorous crop growth. Due to the recent trends in environmental awareness concerning the side effects of herbicides, public pressure is mounting to force industry to develop safer, more environmental friendly approaches for controlling weeds. Microbial-based pesticides, referred to as bioherbicides, for the management of weeds offer such an approach. In majority of the cases, the bioherbicides include fungal organisms as the active ingredients; therefore, the term mycoherbicide has often been used interchangeably with bioherbicide. Considerable progress has been made during the past four decades in the use of fungi as biocontrol agent of weeds. There has been a great number of naturally occurring fungal strains researched for possible use as mycoherbicides, but only a small proportion have been developed to commercial products. Currently, a total of 17 mycoherbicides (8 in the USA, 4 in Canada, 2 in South Africa, and 1 each in the Netherlands, Japan, and China) have been registered around the globe. The advancement of formulation techniques is of paramount importance to the continued development of mycoherbicides. It is also essential to continue intensive screening programs for the selection of fungal pathogens, especially hemibiotrophs, if mycoherbicides are to become a viable component of integrated weed management in the future. Recent trend is the application of several host-specific fungal pathogens in a bioherbicide mixture as a multicomponent bioherbicide system for simultaneous, broad-spectrum weed biocontrol. Many microbes, although they rarely have an effect under natural conditions, can be developed as effective bioherbicides. At Kurukshetra, during the last 30 years, searches for fungal BCAs have been made on 26 weeds (7 aquatic and 19 terrestrial), and a number of them have been evaluated for their biocontrol potential against the notorious weeds of this region. The mycoherbicides which have been commercialized and are in the process of commercialization have been discussed in detail in this chapter.