Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

ObjectivesWe sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.BackgroundEpidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.MethodsA systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.ResultsA total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).ConclusionsThere is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking

Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights From Large Randomized Statin Trials

ObjectivesWe sought to assess the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering and rates of elevated liver enzymes, rhabdomyolysis, and cancer.BackgroundAlthough it is often assumed that statin-associated adverse events are proportional to LDL-C reduction, that assumption has not been validated.MethodsAdverse events reported in large prospective randomized statin trials were evaluated. The relationship between LDL-C reduction and rates of elevated liver enzymes, rhabdomyolysis, and cancer per 100,000 person-years was assessed using weighted univariate regression.ResultsIn 23 statin treatment arms with 309,506 person-years of follow-up, there was no significant relationship between percent LDL-C lowering and rates of elevated liver enzymes (R2<0.001, p = 0.91) or rhabdomyolysis (R2= 0.05, p = 0.16). Similar results were obtained when absolute LDL-C reduction or achieved LDL-C levels were considered. In contrast, for any 10% LDL-C reduction, rates of elevated liver enzymes increased significantly with higher statin doses. Additional analyses demonstrated a significant inverse association between cancer incidence and achieved LDL-C levels (R2= 0.43, p = 0.009), whereas no such association was demonstrated with percent LDL-C reduction (R2= 0.09, p = 0.92) or absolute LDL-C reduction (R2= 0.05, p = 0.23).ConclusionsRisk of statin-associated elevated liver enzymes or rhabdomyolysis is not related to the magnitude of LDL-C lowering. However, the risk of cancer is significantly associated with lower achieved LDL-C levels. These findings suggest that drug- and dose-specific effects are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer

Reconnoitering the role of long-noncoding rnas in hypertrophic cardiomyopathy: A descriptive review

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomy-opathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including MYH7, MYBPC3, ACTC1, TPM1, MYL2, MYL3, TNNI3, and TNNT23. Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding RNAs (lncRNAs) are a large class of transcripts ≥200 nucleotides in length that do not encode proteins. Compared to coding mRNAs, most lncRNAs are not as well-annotated and their functions are greatly unexplored. Nevertheless, increasing evidence shows that lncRNAs are involved in a variety of biological processes and diseases including HCM. Accumulating evidence has indicated that lncRNAs are dysregulated in HCM, and closely related to sarcomere construction, calcium channeling and homeostasis of mitochondria. In this review, we have summarized the known regulatory and functional roles of lncRNAs in HCM

Commotio Cordis

Sudden arrhythmic death as a result of a blunt chest wall blow has been termed Commotio Cordis (CC). CC is being reported with increasing frequency with more than 180 cases now described in the United States Commotio Cordis Registry. The clinical spectrum is diverse; however young athletes tend to be most at risk, with victims commonly being struck by projectiles regarded as standard implements of the sport. Sudden death is instantaneous and victims are most often found in ventricular fibrillation (VF). Chest blows are not of sufficient magnitude to cause any significant damage to overlying thoracic structures and autopsy is notable for the absence of any structural cardiac injury. Development of an experimental model has allowed for substantial insights into the underlying mechanisms of sudden death. In anesthetized juvenile swine, induction of VF is instantaneous following chest impacts that occur during a vulnerable window before the T wave peak. Other critical variables, including the impact velocity and location, and the hardness of the impact object have also been identified. Rapid left ventricular pressure rise following chest impact likely results in activation of ion channels via mechano-electric coupling. The generation of inward current through mechano-sensitive ion channels results in augmentation of repolarization and non-uniform myocardial activation, and is the cause of premature ventricular depolarizations that are triggers of VF in CC. Currently available chest protectors commonly used in sport are not adequately designed to prevent CC. The development of more effective chest protectors and the widespread availability of automated external defibrillators at youth sporting events could improve the safety of young athletes

The Impact of Human Resource Management Practices, Organizational Culture, Motivation and Knowledge Management on Job Performance with Leadership Style as Moderating Variable in the Jordanian Commercial Banks Sector

Abstract: In this paper, the effect of three human resource management practices namely, compensation and benefits, training and development, and performance appraisal and achievement was examined along with organizational culture, motivation and knowledge management on job performance among Jordanian banks. The construct of job performance was measured by the combination of task performance and organizational citizenship behavior. The study employed convenience sampling to which 30 questionnaires were distributed. The finding showed a significant impact of human resource management practices (compensation and benefits, training and development, and appraisal and achievement), organizational culture, motivation and knowledge management on job performance in the Jordanian banks. On the basis of the findings, the researcher provided recommendations for the banks in terms of strengthening the relationship between their knowledge management job performance. The study also provided implications to theory and practice based on the findings.Â

Inflammatory cytokines and atrial fibrillation: current and prospective views

Atrial fibrillation (AF) is the most common sustained arrhythmia and a challenging clinical problem encountered in daily clinical practice. There is an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions including AF. Historical evidence supports an association between AF and inflammation and is consistent with the association of AF with inflammatory conditions of the heart, such as myocarditis and pericarditis. AF has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. Increased plasma interleukin (IL)-6, C-reactive protein (CRP), and plasma viscosity support the existence of an inflammatory state among “typical” populations with chronic AF. These indexes of inflammation are related to the prothrombotic state and may be linked to the clinical characteristics of the patients (underlying vascular disease and comorbidities), rather than simply to the presence of AF itself. It has been suggested that inflammation may have a role in the development of atrial arrhythmias after cardiac surgery, and that a genetic predisposition to develop postoperative complications exists. Cytokines can have a prognostic significance; IL-6 levels, CRP, and other cytokines may have prognostic value in AF. Cytokine lowering therapies, statins, angiotensin converting enzyme inhibitors and other anti-inflammatory agents may have a role in the treatment of AF. The present article provides an overview of the evidence linking inflammatory cytokines to AF and their therapeutic and prognostic implications

Regulation of Angiotensin- Converting Enzyme 2 in Obesity: Implications for COVID-19

The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2

Desulphurization of Simulated Oil Using SAPO-11 with CNT's as Adsorbent: A Kinetic Study

In this study, sulfur was removed from imitation oil using oxidative desulfurization process. Silicoaluminophosphate (SAPO-11) was prepared using the hydrothermal method with a concentration of carbon nanotubes (CNT) of 0% and 7.5% at 190 °C crystallization temperature. The final molar composition of the as-prepared SAPO-11 was Al2O3: 0.93P2O5: 0.414SiO2. 4% MO/SAPO-11 was prepared using impregnation methods. The produced SAPO-11 was described using X-ray diffraction (XRD) and Brunauer-Emmet-Teller (N2 adsorption–desorption isotherms). It was found that the addition of CNT increased the crystallinity of SAPO-11. The results showed that the surface area of SAPO-11 containing 7.5% CNT was 179.54 m2/g, and the pore volume was 0.317 cm3/g. However, the surface area of SAPO-11 containing 0% CNT was 125.311 m2/g, and pore volume was 0.275 cm3/g, while nanoparticles with an average particle diameter of 24.8 nm were obtained. Then, the prepared SAPO-11 was used in the oxidative desulfurization process. The oxidative desulfurization was studied using several factors affecting desulfurization efficiency, such as time (40, 60, 80, 100, and 120) min, amount of MO/SAPO-11 (0.3, 0.4, 0.5, 0.6, and 0.7) g/100 ml of simulated oil (100 ppm of dibenzothiophene), the amount of hydrogen peroxide (4ml) oxidizer/100 ml of simulated oil, and the temperature ranges from (40, 50, 60, 70, and 80 °C). The results showed that an increase in MO/SAPO-11 led to an increase in desulfurization. The best removal percentage for sulfur content was 92.79%, obtained at 70 °C and 0.6 g of MO/SAPO-11 containing 7.5% CNT, and the removal was 82.34% at 0% CNT and the same other conditions. While the equilibrium was achieved after 100 min. The results revealed that Freundlich's model described the adsorption of sulfur compounds better than Langmuir's, where the R2 of the Freundlich model was 0.9979 and the R2 of the Langmuir model was 0.9554

Case-finding of chronic obstructive pulmonary disease with questionnaire, peak flow measurements and spirometry : a cross-sectional study

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