Relationship between adiponectin and copeptin levels with long-term cardiovascular mortality in ST-segment elevation myocardial infarction after percutaneous coronary intervention.

OBJECTIVE: The aim of this study was to determine adiponectin and copeptin levels that might be prognostic for cardiovascular mortality (CvsM) in ST-segment elevation myocardial infarction (STEMI) patients who had percutaneous coronary intervention (PCI). METHODS: Patients who underwent PCI between November 2010 and April 2011 were enrolled and followed for more than eight years. The baseline, demographic and angiographic findings, in-hospital follow up, laboratory results including adiponectin and copeptin levels, and echocardiographic data of the patients were evaluated. RESULTS: There were 78 males and 20 females. The CvsM rate was 26.66% at 112 months of follow up. Some factors were significantly related to CvsM and adiponectin level was an independent predictor of mortality. A cut-off value of ≥ 8 950 ng/ml for adiponectin and ≥ 7.41 ng/ml for copeptin was related to a 3.01- and 2.83-times higher CvsM risk, respectively. CONCLUSION: Adiponectin level was a predictor for CvsM. Higher levels of adiponectin and copeptin could predict a higher risk of CvsM in STEMI patients.

Admission triglyceride-glucose index is predictor of long-term mortality and appropriate implantable cardiac defibrillator therapy in patients with heart failure.

Background: In this study, the main aim was to evaluate the relation of the triglyceride-glucose (TyG) index to long-term mortality and proper shock therapy in patients with an implantable cardiac defibrillator (ICD) implanted for heart failure with reduced ejection fraction. Methods: This retrospective study group consisted of 773 patients treated with ICD for heart failure with reduced ejection fraction. The long-term prognostic effect of the TyG index among tertiles was evaluated regarding mortality and appropriate ICD therapy. Results: In the adjusted model, the mortality rates were 14.0% (hazard ratio: 2.24; 95% CI: 1.42-6.88) in tertile 2 and 23.3% (hazard ratio: 3.88; 95% CI: 1.84-14.38) in tertile 3. Conclusion: The TyG index was found to be an independent predictive marker for both long-term mortality and appropriate ICD therapy.

Synchrotron radiation photoemission spectroscopy of the oxygen modified CrCl3 surface.

We investigate the experimentally challenging CrCl3 surface by photon energy dependent photoemission (PE). The core and valence electrons after cleavage of a single crystal, either in a ultra-high vacuum (UHV) or in air, are studied by keeping the samples at 150 °C, aiming at confirming the atomic composition with respect to the expected bulk atomic structure. A common spectroscopic denominator revealed by data is the presence of a stable, but only partially ordered Cl-O-Cr surface. The electronic core levels (Cl 2p, Cr 2p and 3p), the latter ones of cumbersome component determination, allowed us to quantify the electron charge transfer to the Cr atom as a net result of this modification and the increased exchange interaction between metal and ligand atoms. In particular, the analysis of multiplet components by the CMT4XPS code evidenced the charge transfer to be favored, and similarly the reduced crystal field due to the established polarization field. Though it is often claimed that a significant amount of Cl and Cr atomic vacancies has to be included, such a possibility can be excluded on the basis of the sign and the importance of the shift in the binding energy of core level electrons. The present methodological approach can be of great impact to quantify the structure of ordered sub-oxide phases occurring in mono or bi-layer Cr trihalides.

Mechanical exfoliation and layer number identification of single crystal monoclinic CrCl3.

After the recent finding that CrI3, displays ferromagnetic order down to its monolayer, extensive studies have followed to pursue new two-dimensional (2D) magnetic materials. In this article, we report on the growth of single crystal CrCl3 in the layered monoclinic phase. The system after mechanical exfoliation exhibits stability in ambient air (the degradation occurs on a time scale at least four orders of magnitude longer than is observed for CrI3). By means of mechanical cleavage and atomic force microscopy (AFM) combined with optical identification, we demonstrate the systematic isolation of single and few layer flakes onto 270 nm and 285 nm SiO2/Si (100) substrates with lateral size larger than graphene flakes isolated with the same method. The layer number identification has been carried with statistically significant data, quantifying the optical contrast as a function of the number of layers for up to six layers. Layer dependent optical contrast data have been fitted within the Fresnel equation formalism determining the real and imaginary part of the wavelength dependent refractive index of the material. A layer dependent (532 nm) micro-Raman study has been carried out down to two layers with no detectable spectral shifts as a function of the layer number and with respect to the bulk.

Characterization of liver specific promoters in a foamy viral vector pMD09.

Foamy viruses (FVs) or spumaviruses are retroviruses that are explored as vectors for gene therapy. The good feature of foamy viruses is its broad tropism; however, their infections result in non-targeted gene expression. Here, we attempted to design the liver targeted viral gene delivery by employing liver specific gene promoters like albumin (ALB), transthyretin (TTR) and hepatitis B virus (HBV) promoters. We compared the relative gene expression of liver specific promoters versus the U3 promoter in liver cell line (HepG2) and non-liver cell lines: human fibrosarcoma cell line (HT1080), baby hamster kidney cell line (BHK), human embryonic kidney cell line (HEK 293T) and cervical cancer cell line (HeLa). We have found that the promoter exchange didn't affect viral assembly. The ability to drive gene expression was best with TTR promoter which was followed by HBV and ALB promoter. The use of TTR, HBV and ALB promoters are helpful in achieving liver specific gene expression. Keywords: foamy virus; gene therapy; liver; albumin; transthyretin promoter; HBV promoter.

A comparative study of hepatitis B virus X protein mutants K130M, V131I and KV130/131MI to investigate their roles in fibrosis, cirrhosis and hepatocellular carcinoma.

Hepatitis B virus (HBV) genomic mutations A1762T, G1764A and AG1762/1764TA cause production of HBV X protein (HBx) mutants, namely K130M, V131I and KV130/131MI. These mutations are important biomarkers for the development of cirrhosis and hepatocellular carcinoma (HCC) in chronic HBV patients. This study comparatively analyses the impact of intracellular expression of HBx mutants on HCC cell line Huh7. It was found that expression of KV130/131MI induced: cell proliferation, altered expression of cell cycle regulatory genes in favour of cell proliferation, intracellular reactive oxygen species (ROS) production and mitochondrial depolarization. KV130/131MI may be directly involved in host cell proliferation and hepatocarcinogenesis via altering expression of cell cycle regulatory genes. KV130/131MI may also play pivotal roles in fibrosis and cirrhosis via inducing ROS production and mitochondrial depolarization. Furthermore, these might be the possible reasons for higher occurrence of AG1762/1764TA as compared to A1762T and G1764A in cirrhosis and HCC patients.

Are inflammatory parameters predictors of amputation in acute arterial occlusions?

Background The aim of the present study was to investigate the role of inflammatory markers to predict amputation following embolectomy in acute arterial occlusion. Methods A total of 123 patients operated for arterial thromboembolectomy due to acute embolism were included in the study. The patients without an extremity amputation following thromboembolectomy were classified as Group 1 ( n = 91) and the rest were classified as Group 2 ( n = 32). These groups were compared in terms of clinical and demographic characteristics, C-reactive protein, complete blood count parameters, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red cell distribution width. Results The average age was 68.0 ± 11.7 years. The most common thromboembolism localization was femoral artery. When preoperative mean C-reactive protein ( p = 0.0001), mean platelet volume ( p = 0.0001), platelet-lymphocyte ratio ( p = 0.0001), neutrophil-lymphocyte ratio ( p = 0.0001) and red cell distribution width ( p = 0.0001) were compared, a statistically significant difference was observed between groups. In univariate and multivariate regression analysis, higher levels of preoperative C-reactive protein ( p = 0.009) and mean platelet volume ( p = 0.04) were detected as independent risk factors of early extremity amputation. Conclusion We observed that preoperative mean platelet volume and C-reactive protein were predictors of amputation after thromboembolectomy in acute arterial occlusion.

Occurrence of co-infection with dengue viruses during 2014 in New Delhi, India.

Dengue fever is an arthropod-borne viral infection that has become endemic in several parts of India including Delhi. We studied occurrence of co-infection with dengue viruses during an outbreak in New Delhi, India in 2014. For the present study, blood samples collected from symptomatic patients were analysed by RT-PCR. Eighty percent of the samples were positive for dengue virus. The result showed that DENV-1 (77%) was the predominant serotype followed by DENV-2 (60%). Concurrent infection with more than one serotype was identified in 43% of the positive samples. Phylogenetic analysis clustered DENV-1 strains with the American African and DENV-2 strains in Cosmopolitan genotypes. Four common amino-acid mutations were identified in the envelope gene of DENV-1 sequences (F337I, A369T, V380I and L402F) and one common mutation (N390S) in the DENV-2 sequences. Further analysis revealed purifying selection in both the serotypes. A significant number of patients were co-infected with DENV-1 and DENV-2 serotypes. Although we do not have direct evidence to demonstrate co-evolution of these two stereotypes, nonetheless their simultaneous occurrence does indicate that they are favoured by evolutionary forces. An ongoing surveillance and careful analysis of future outbreaks will strengthen the concept of co-evolution or otherwise. Whether the concurrent dengue viral infection is correlated with disease severity in a given population is another aspect to be pursued. This study is envisaged to be useful for future reference in the context of overall epidemiology.

Association of admission serum laboratory parameters with new-onset atrial fibrillation after a primary percutaneous coronary intervention.

OBJECTIVES: New-onset atrial fibrillation (NOAF) during hospitalization is considered a frequent complication associated with worse outcomes in the setting of ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the association of admission serum laboratory parameters, neutrophil to lymphocyte ratio (NLR), and monocyte to high-density lipoprotein ratio (MHR) with NOAF in STEMI patients treated with a primary percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 621 patients who were hospitalized with a diagnosis of STEMI and treated with primary PCI were retrospectively enrolled in the study. NOAF during index hospitalization and overall mortality were reported as the clinical outcomes. RESULTS: In our study population, 40 (6.4%) patients developed NOAF during index hospitalization. Monocyte counts, mean platelet volume (MPV), red cell distribution width (RDW), NLR, MHR, C-reactive protein (CRP), creatinine, glucose, and uric acid levels were higher in the NOAF+ group compared with the NOAF- group. In multivariate regression analysis, age, left-ventricular ejection fraction, left atrial volumes, admission heart rate, multivessel disease, increased levels of CRP, MPV, RDW, uric acid, NLR, and MHR independently predicted NOAF. In addition, NOAF was found to be an independent predictor of overall mortality in the study population. CONCLUSION: For the first time in the literature, admission serum levels of MPV, RDW, uric acid, NLR, and MHR were found to be correlated independently with NOAF after primary PCI.

The neutrophil-to-lymphocyte ratio is associated with bare-metal stent restenosis in STEMI patients treated with primary PCI.

BACKGROUND: The clinical importance of complete blood count (CBC) parameters such as the neutrophil-to-lymphocyte ratio (NLR) has been shown in cardiovascular diseases. Stent restenosis (SR) is a major adverse event after stent implantation. In this study, we aimed to investigate the correlation of CBC parameters with SR rates after primary percutaneous coronary intervention (PCI). METHODS: Patients who had undergone primary PCI for ST-segment elevation myocardial infarction (STEMI) and control angiography during follow-up were retrospectively recruited. Patients were categorized according to admission NLR tertiles, and clinical, hematological, and angiographic data were compared. RESULTS: A total of 404 patients (207 patients with SR and 197 patients without SR) were included in the study. Patients were categorized into three groups according to the tertiles of admission NLRs; the NLR was less than 3.38 in tertile 1 (n=134), between 3.38 and 6.26 in tertile 2 (n=135), and greater than 6.26 in tertile 3 (n=135). During a follow-up period of a median of 14 months (minimum 6 months, maximum 60 months) SR developed in 80 patients of tertile 3 (59%), 74 patients of tertile 2 (55%), and 53 patients of tertile 1 (40%), which were significantly different (P=0.01). According to multivariate Cox regression analysis, male sex, stent length (odds ratio 1.04, 95% confidence interval 1.01-1.06, P=0.01), admission NLRs (odds ratio 1.13, 95% confidence interval 1.08-1.19, P=0.01), and white blood cell and neutrophil counts remained the independent predictors of SR in the study population. Other CBC parameters and admission C-reactive protein, creatinine, and fasting glucose levels were not independently correlated with SR. On receiver operating curve analysis, admission NLRs higher than 3.84 were found to predict SR with a sensitivity of 73.4% and a specificity of 50.8% (area under the curve 0.604, P=0.01). CONCLUSION: High NLR levels, white blood cell counts, and neutrophil counts at admission are independently correlated with SR after primary PCI.

Can the T-peak to T-end interval be a predictor of mortality in patients with ST-elevation myocardial infarction?

BACKGROUND: The interval between the peak and the end of the T wave (Tp-e interval) on 12-lead ECG is a measure of transmural dispersion of repolarization and may be related to malignant ventricular arrhythmias. The objective of this study was to investigate whether the Tp-e interval predicts in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing a primary percutaneous coronary intervention (pPCI). METHODS: This study included 488 consecutive patients with STEMI treated with pPCI. Electrocardiograms were obtained after pPCI and the Tp-e interval was measured in leads without ST-segment elevation. RESULTS: There were 46 (9.4%) deaths in the population, with a mean follow-up time of 21.1±10.2 months. The Tp-e interval was associated with not only in-hospital ventricular tachycardia/fibrillation, target vessel revascularization, and death but also long-term target vessel revascularization and death. Furthermore, the Tp-e interval measured using the tail method was found to be a significant predictor of long-term mortality in multivariable Cox analyses [odds ratio 1.018, 95% confidence interval (1.004-1.033)]. Findings were similar in the Tp-e interval and the heart rate-corrected Tp-e interval (cTp-e). CONCLUSION: Tp-e and cTp-e measured using the tail method were found to be predictors of both in-hospital and long-term mortality.

Evaluation of coronary microvascular function and nitric oxide synthase intron 4a/b polymorphism in patients with coronary slow flow.

OBJECTIVE: Slow coronary flow (SCF) is reported to be associated with increased risk of cardiovascular disease. We have used coronary flow reserve measurement by transthoracic Doppler echocardiography to determine coronary microvascular function in patients with SCF and to determine whether the intron 4a/b polymorphism of the eNOS gene influences coronary endothelial function. METHODS: Overall, 96 patients with SCF and 79 controls were enrolled in the study. Coronary flow was quantified according to the thrombolysis in myocardial infarction (TIMI) frame count (TFC) on angiogram. Coronary diastolic peak flow velocities (DPFV) were measured with color Doppler flow mapping at baseline and after dipyridamole infusion. Coronary flow reserve was calculated as the ratio of hyperemic to baseline DPFV. The eNOS 4a/b polymorphism was detected by PCR. Patients with diabetes were excluded from the study. RESULTS: The SCF group was comparable to the control group in terms of demographic and clinical characteristics, except for hemoglobin and HDL-cholesterol levels, TFC of the left anterior descending artery, the circumflex artery, and the right coronary artery; the mean TFC was higher in the SCF group. Hyperemic DPFV and the hyperemic/baseline DPFV ratio were significantly lower in the SCF group when compared with the control group. However, baseline DPFV were similar in both groups. The number of patients with eNOS4 a/a and eNOS4 a/b phenotypes was statistically higher in SCF groups. The frequency of allele 'a' of the eNOS4 gene was also statistically higher in the SCF group. When patients were grouped according to the presence or absence of allele 'a' of the eNOS4 gene, statistically significant differences were found in the TFC of the left anterior descending artery, the circumflex artery; mean TFC; baseline DPFV; and hyperemic/baseline DPFV. Univariate analysis in which eNOS4 b/b was used as the referent group showed that the presence of allele 'a' of the eNOS4 gene significantly predicted SCF (odds ratio: 2.79, 95% confidence interval: 1.32-5.89; P=0.007). In multivariate analysis using a model adjusted for variables with a P value lower than 0.10 in univariate analyses, the presence of allele 'a' of the eNOS4 gene was found to be an independent predictor of SCF (odds ratio: 3.22, 95% confidence interval: 1.28-8.82; P=0.013). CONCLUSION: The presence of allele 'a' may be a risk factor for microvascular endothelial dysfunction and higher TFCs in SCF patients.

Assessment of interleukin-1 gene cluster polymorphisms in lone atrial fibrillation: new insight into the role of inflammation in atrial fibrillation.

BACKGROUND: Systemic inflammation is accepted as one of the pathophysiological mechanisms of atrial fibrillation (AF). The role of inflammation has been shown previously. Interleukin (IL) system is the main modulator of the inflammatory responses and genetic polymorphisms of IL-1 cluster genes are associated with increased risk for inflammatory diseases. OBJECTIVES: To investigate the association between polymorphisms of IL-1 cluster genes and lone AF. SUBJECTS AND METHODS: DNA samples were collected from 70 proven lone AF patients and 70 healthy subjects. Genomic DNA was typed for the variable number of the tandem repeat (VNTR) IL-1 receptor antagonist (RN) gene polymorphism, IL-1B -511 C > T(rs16944) promoter polymorphism, and +3953 C > T(rs1143634) polymorphism in exon 5 by polymerase chain reaction. RESULTS: In lone AF group the frequency of IL-1RN2/2 and IL-1RN1/2 genotypes were higher than in the control group (7.2% vs 4.3% and 48.5% vs 22.8%, respectively; χ(2) = 14.1; P = 0.028). The frequency of allele 2 was significantly higher in the lone AF group (32.1% vs 15.7%; χ(2) = 10.7; P = 0.005). Allele and genotype distribution of IL-1B -511 C > T and +3953 C > T polymorphisms were not statistically different between the groups. C-reactive protein (CRP) levels were higher in lone AF patients compared to the control group (median = 1.25, interquartile range [IQR] = 0.85 vs median = 1.08, IQR 0.46 mg/L, respectively; P = 0.02). In multivariate regression analysis, presence of allele 2 of IL-1 VNTR polymorphism and elevated plasma high-sensitive-CRP levels were the independent predictors of lone AF. CONCLUSION: Presence of allele 2 of VNTR polymorphism of IL-1RN gene may cause increased risk for lone AF probably due to the inadequate limitation of inflammatory reactions.

Role of HBV genotype in predicting response to lamivudine therapy in patients with chronic hepatitis B.

BACKGROUND: Predictors of response of chronic hepatitis B (CHB) to lamivudine therapy need better definition. Whether hepatitis B virus (HBV) genotypes could serve as such a predictor has not been well studied. AIM: To study the association of HBV genotypes with the outcome of lamivudine treatment in patients with CHB. METHODS: Seventy-six patients with CHB (45 HBeAg +ve) received lamivudine 100 mg/day, orally for 12 mo. Infecting HBV genotypes were determined in pre-treatment specimens using restriction fragment length polymorphism. End-of-treatment response (ETR) and sustained viral response (SVR) were defined as undetectable HBV DNA (< 0.5 pg/mL) at 12 and 18 months, respectively. RESULTS: ETR was observed in 26 (34%) and SVR in 11 (14%) patients receiving lamivudine. The pre-treatment characteristics of the responders and non-responders were comparable. Genotypes A and D were observed in 28 (37%) and 48 (63%) patients, respectively. The frequency of genotypes A and D was comparable between responders (28.6% vs. 37.5%) and non-responders (71.4% vs. 62.5%), respectively (p=ns). Of the 26 responders, SVR could be evaluated in 20 subjects; 9 (45%) relapsed and 11 achieved SVR. Patients with genotype D achieved higher SVR rate than genotype A (10 of 48, 28.8% vs. 1 of 28, 3.5% p =0.0359). CONCLUSIONS: Forty-five percent of Indian patients with CHB who achieve ETR relapse, and SVR to lamivudine therapy is achieved in 14%. Patients with genotype D achieve higher SVR rate than with genotype A.

Base-pair alterations in the epsilon-lower stem due to a novel double substitution in the precore gene of HBV-e negative variant were recovered by secondary mutations.

The HBe negative phenotype, a natural precore mutant (G1896A/G1897A) of HBV with aborted HBeAg expression is known to cause chronic hepatitis. The destabilized C : G base-pairing in the lower stem of epsilon-hairpin due to G1896A substitution is reportedly compensated by a second C1858T mutation and suggested to play an important role in enhanced selection of the HBe negative variant. We undertook to investigate presence of such compensatory mutations at other positions by analyzing epsilon-sequences (nts. 1847-1907) as well as to look for their effect(s), if any, on the consensus sequence of the overlapping core-initiator of HBe negative HBV variants in CLD patients. Three of the 5 HBe negative patients had classical G1896A mutation having a second compensatory mutation at nt. 1858. One patient showed an additional G1897A substitution, presenting as a novel precore stop codon mutation (UGG-->UAA), followed by a compensatory mutation at position 1857. In the third patient, a G1899A substitution was seen which compensated the impaired U at position 1855. Other substitution and deletion mutations were also observed in the remaining epsilon-hairpin, which however, did not produce any compensatory mutation. Further, all the precore variants showed a conserved G at position 1904, important for the optimal context of their core-initiator which however, remained impaired with A (nt. 1850). Our results suggest that the nts. 1851-1859 and nts. 1895-1904 in the lower stem, and restoration of authentic base-pairings therein, maintain the structural integrity and stability of the epsilon-hairpin. This may have a role in the enhanced selection of the HBe negative variants and persistence of HBV infection in chronic liver disease patients.

Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis.

BACKGROUND/AIMS: HBV-related chronic liver disease patients often present with hepatic decompensation and are not eligible for interferon therapy. Whether long-term lamivudine is effective in these patients was prospectively evaluated. METHODS: Eighteen patients with HBV-related decompensated cirrhosis, all with quantitative DNA +ve and 10 HBeAg +ve, were given lamivudine 150 mg/d. RESULTS: Each patient received at least 9 months (mean 17.9) of lamivudine. Three HBeAg+ve patients (30%) seroconverted to anti-HBe and one lost HBsAg during the follow-up. An improvement from baseline in the aspartate aminotransferase (130 vs. 72 IU/l, p<0.04); alanine aminotransferase (111 vs. 58 IU/l, p<0.01) and Child-Pugh score (8.3 vs 6.7, p<0.013) was seen. Lamivudine had no significant side-effects. HBV DNA became undetectable in all patients by 8 weeks of therapy. In three (17%) patients, HBV DNA again became positive at 9, 9 and 27 months. YMDD mutant was, however, detected in only one (6%). A significant reduction was noted in the morbidity and hospitalizations for complications of liver disease before and after starting lamivudine (1.5+/-0.7 vs. 0.6+/-0.7, p<0.002). CONCLUSIONS: In decompensated HBV-related cirrhosis, lamivudine: i) is effective in suppressing HBV DNA and seroconversion to anti-HBe (30%), ii) can achieve significant improvement in clinical and biochemical status of liver functions.

Lithium and anti-viral drug toxicity: II. Further studies on the ability of lithium to modulate the hematopoietic toxicity associated with the anti-viral drug zidovudine (AZT).

Lithium is an agent capable of influencing many aspects of blood cell production, in particular, the formation of granulocytes. Because of this property, lithium has been demonstrated to be an effective agent whenever granulocyte production is either faulty or inadequate. The anti-viral drug zidovudine (AZT) has used been extensively in the treatment of acquired immune deficiency syndrome (AIDS). However, its effectiveness is limited because of the myelosuppression and bone marrow toxicity associated with its use. We have previously demonstrated that lithium, when combined with AZT in vitro with normal bone marrow cells or when administered in vivo to mice receiving dose-escalation AZT, reduced the myelosuppression and marrow toxicity of AZT significantly. We report here further studies designed to evaluate the extent of lithium's capacity to modulate AZT toxicity by investigating the ability of lithium to influence blood cell production when administered to normal mice during an initial exposure to AZT. C57BL6 were administered dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a period of 4-weeks in the presence or absence of lithium carbonate (1 mM). This was followed by an additional 4-week period during which mice received only AZT. Animals were analyzed on a weekly basis for their peripheral blood indices. Animals receiving dose-escalation AZT demonstrated anemia, thrombocytopenia, and neutropenia which was dose-related. During the period when animals received combination lithium/AZT, there was significantly less anemia, thrombocytopenia, and neutropenia as compared to the AZT controls.(ABSTRACT TRUNCATED AT 250 WORDS)