ASSESSMENT OF CORRELATION IN GENDER AND AGE WITH LIPOPROTEIN LEVELS IN HYPERLIPIDEMIA PATIENTS

ABSTRACTObjective: The main objective of the study was to monitor and compare the correlation between the age and gender with the serum lipoprotein levelsin the hyperlipidemia patients.Methods: The entire study was performed only after getting approval from the Institutional Ethics Committee. This is a prospective observationalstudy and conducted in Department of Cardiology of a tertiary care teaching hospital. A total of 520 patients were included and the data collected bydata entry form, and the results were thoroughly analyzed using various statistical tools for its relevance and significance.Results: From the total study population (n=520), the majority was males 271 (52.1%) than the female population 249 (47.9%). The minimum agein the study population identified was 40 (years) and the maximum age was 89 (years). The average age of the study population was found to be60.94±13.062 (years). The mean averages of total cholesterol in males 217.48±39.33 mg/dL compared to females 231.05±55.05 mg/dL, triglyceridesin males were 209.01±73.08 mg/dL compared to females 235.71±97.16 mg/dL, low-density lipoproteins in males were 156.42±37.02 mg/dLcompared to females 164.19±43.17 mg/dL, and in case of high-density lipoproteins it was 32.61±6.34 mg/dL compared to females 31.48±6.53 mg/dL.Conclusion: From the entire study, it was concluded that the prevalence rate is a more common in male population. The incidence rate is too high inyounger age population. The correlation of age and gender is directly proportional to the incidence of hyperlipidemia.Keywords: Hyperlipidemia, Cardiology, Gender, Age

Gauged Flavor Group with Left-Right Symmetry

We construct an anomaly-free extension of the left-right symmetric model, where the maximal flavor group is gauged and anomaly cancellation is guaranteed by adding new vectorlike fermion states. We address the question of the lowest allowed flavor symmetry scale consistent with data. Because of the mechanism recently pointed out by Grinstein et al. tree-level flavor changing neutral currents turn out to play a very weak constraining role. The same occurs, in our model, for electroweak precision observables. The main constraint turns out to come from WR-mediated flavor changing neutral current box diagrams, primarily K - Kbar mixing. In the case where discrete parity symmetry is present at the TeV scale, this constraint implies lower bounds on the mass of vectorlike fermions and flavor bosons of 5 and 10 TeV respectively. However, these limits are weakened under the condition that only SU(2)_R x U(1)_{B-L} is restored at the TeV scale, but not parity. For example, assuming the SU(2) gauge couplings in the ratio gR/gL approx 0.7 allows the above limits to go down by half for both vectorlike fermions and flavor bosons. Our model provides a framework for accommodating neutrino masses and, in the parity symmetric case, provides a solution to the strong CP problem. The bound on the lepton flavor gauging scale is somewhat stronger, because of Big Bang Nucleosynthesis constraints. We argue, however, that the applicability of these constraints depends on the mechanism at work for the generation of neutrino masses.Comment: 1+23 pages, 1 table, 5 figures. v3: some more textual fixes (main change: discussion of Lepton Flavor Violating observables rephrased). Matches journal versio

Flavor Physics in an SO(10) Grand Unified Model

In supersymmetric grand-unified models, the lepton mixing matrix can possibly affect flavor-changing transitions in the quark sector. We present a detailed analysis of a model proposed by Chang, Masiero and Murayama, in which the near-maximal atmospheric neutrino mixing angle governs large new b -> s transitions. Relating the supersymmetric low-energy parameters to seven new parameters of this SO(10) GUT model, we perform a correlated study of several flavor-changing neutral current (FCNC) processes. We find the current bound on B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on the lightest Higgs boson mass implies an important lower bound on tan beta, which in turn limits the size of the new FCNC transitions. Remarkably, the combined analysis does not rule out large effects in B_s-B_s-bar mixing and we can easily accomodate the large CP phase in the B_s-B_s-bar system which has recently been inferred from a global analysis of CDF and DO data. The model predicts a particle spectrum which is different from the popular Constrained Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces heavy masses, typically above 1 TeV, for the sfermions of the degenerate first two generations. However, the ratio of the third-generation and first-generation sfermion masses is smaller than in the CMSSM and a (dominantly right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes, Fig. 2 corrected; journal versio

The flavor puzzle in multi-Higgs models

We reconsider the flavor problem in the models with two Higgs doublets. By studying two generation toy models, we look for flavor basis independent constraints on Yukawa couplings that will give us the mass hierarchy while keeping all Yukawa couplings of the same order. We then generalize our findings to the full three generation Standard Model. We find that we need two constraints on the Yukawa couplings to generate the observed mass hierarchy, and a slight tuning of Yukawa couplings of order 10%, much less than the Standard Model. We briefly study how these constraints can be realized, and show how flavor changing currents are under control for $K-\bar{K}$ mixing in the near-decoupling limit.Comment: 26 pages, typos are corrected, references are added, the final versio

Supersymmetric constraints from Bs -> mu+mu- and B -> K* mu+mu- observables

We study the implications of the recent LHCb limit and results on Bs -> mu+mu- and B -> K* mu+mu- observables in the constrained SUSY scenarios. After discussing the Standard Model predictions and carefully estimating the theoretical errors, we show the constraining power of these observables in CMSSM and NUHM. The latest limit on BR(Bs -> mu+mu-), being very close to the SM prediction, constrains strongly the large tan(beta) regime and we show that the various angular observables from B -> K* mu+mu- decay can provide complementary information in particular for moderate tan(beta) values.Comment: 30 pages, 14 figure

Proximal correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum

Extent: 11p.OBJECTIVE: To examine the social and behavioural correlates of metabolic phenotypes during ‘at-risk’ and ‘case’ stages of the metabolic disease continuum. DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A total of 718 community-dwelling adults (57% female), aged 18--92 years from a regional South Australian city. MEASUREMENTS: Total body fat and lean mass and abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting venous blood was collected in the morning for assessment of glycated haemoglobin, plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet (96-item food frequency), sleep duration and frequency of sleep disordered breathing (SDB) symptoms, and family history of cardiometabolic disease, education, lifetime occupation and household income were assessed by questionnaire. Current medications were determined by clinical inventory. RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had known diabetes (‘cases’), otherwise were classified as the ‘at-risk’ population. In both ‘at-risk’ and ‘cases’, four major metabolic phenotypes were identified using principal components analysis that explained over 77% of the metabolic variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other phenotypes in ‘cases’, whereas all phenotypes were inter-correlated in the ‘at-risk’. Over and above other socioeconomic and behavioural factors, medications were the dominant correlates of all phenotypes in ‘cases’ and SDB symptom frequency was most strongly associated with FMI, LLM and GLY phenotypes in the ‘at-risk’. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to be most strongly predictive of diabetes development. Reducing SDB symptom frequency and optimising the duration of sleep may be important concomitant interventions to standard diabetes risk reduction interventions. Prospective studies are required to examine this hypothesis.MT Haren, G Misan, JF Grant, JD Buckley, PRC Howe, AW Taylor, J Newbury and RA McDermot

Proximal correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum

Extent: 11p.OBJECTIVE: To examine the social and behavioural correlates of metabolic phenotypes during ‘at-risk’ and ‘case’ stages of the metabolic disease continuum. DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A total of 718 community-dwelling adults (57% female), aged 18--92 years from a regional South Australian city. MEASUREMENTS: Total body fat and lean mass and abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting venous blood was collected in the morning for assessment of glycated haemoglobin, plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet (96-item food frequency), sleep duration and frequency of sleep disordered breathing (SDB) symptoms, and family history of cardiometabolic disease, education, lifetime occupation and household income were assessed by questionnaire. Current medications were determined by clinical inventory. RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had known diabetes (‘cases’), otherwise were classified as the ‘at-risk’ population. In both ‘at-risk’ and ‘cases’, four major metabolic phenotypes were identified using principal components analysis that explained over 77% of the metabolic variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other phenotypes in ‘cases’, whereas all phenotypes were inter-correlated in the ‘at-risk’. Over and above other socioeconomic and behavioural factors, medications were the dominant correlates of all phenotypes in ‘cases’ and SDB symptom frequency was most strongly associated with FMI, LLM and GLY phenotypes in the ‘at-risk’. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to be most strongly predictive of diabetes development. Reducing SDB symptom frequency and optimising the duration of sleep may be important concomitant interventions to standard diabetes risk reduction interventions. Prospective studies are required to examine this hypothesis.MT Haren, G Misan, JF Grant, JD Buckley, PRC Howe, AW Taylor, J Newbury and RA McDermot

Prognostic or predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1

Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)). Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation and the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%) and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02,p<0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). Notably, NOTCH1 mutation status separates patients with a strong and a weak benefit from ofatumumab addition to CHL (NOTCH1wt:HR0.50,p<0.01, NOTCH1mut:HR0.81,p=0.45). In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial. These results validate NGS-based mutation analysis in a multicenter trial and provide a basis for expanding molecular testing in the prognostic workup of patients with CLL. ClinicalTrials.gov registration number: NCT0074818

Bub3 Is a Spindle Assembly Checkpoint Protein Regulating Chromosome Segregation during Mouse Oocyte Meiosis

In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1–3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed