Structural modeling and gene expression analysis of phosvitinless vitellogenin (vgc) in the Indian freshwater murrel, Channa punctatus (Bloch, 1793).

Vitellogenin (Vg) is a female-specific egg-yolk precursor protein, synthesized in the liver of fish in response to estrogens. In the present study, complete gene of phosvitinless vitellogenin (vgc) was sequenced, its 3D structure was predicted and validated by web-based softwares. The complete nucleotide sequence of vgc was 4126 bp which encodes for 1272 amino acids and showed the presence of three conserved domains viz. LPD_N, DUF1943 and DUF1944. The retrieved amino acid sequence of VgC protein was subjected to in silico analysis for understanding the structural and functional properties of protein. mRNA levels of multiple vg genes have also been quantified during annual reproductive cycle employing qPCR. A correlation has been observed between seasonal changes in gonadosomatic index with estradiol levels and hepatic expression of three types of vg genes (vga, vgb, vgc) during ovarian cycle of murrel. During preparatory phase, when photoperiod and temperature are low; low titre of E2 in blood induces expression of vgc gene. A rapid increase in the levels of E2 favours induction of vgb and vga genes in liver of murrel during early pre-spawning phase when photoperiod is long and temperature is high in nature. These results suggest that among three vitellogenin proteins, VgC is synthesized earlier than VgA and VgB during oogenesis.

Hemoglobin A1c and Cardiovascular Outcomes Following Percutaneous Coronary Intervention: Insights From a Large Single-Center Registry.

OBJECTIVES: The aim of this study was to evaluate post-percutaneous coronary intervention (PCI) outcomes in relation to pre-procedural glycated hemoglobin (HbA1c) levels from a large, contemporary cohort. BACKGROUND: There are limited data evaluating associations between HbA1c, a marker of glycemic control, and ischemic risk following PCI. METHODS: All patients with known HbA1c levels undergoing PCI at a single institution between 2009 and 2017 were included. Patients were divided into 5 groups on the basis of HbA1c level: ≤5.5%, 5.6% to 6.0%, 6.1% to 7.0%, 7.1% to 8.0%, and >8.0%. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death or myocardial infarction (MI), at 1-year follow-up. RESULTS: A total of 13,543 patients were included (HbA1c ≤5.5%, n = 1,214; HbA1c 5.6% to 6.0%, n = 2,202; HbA1c 6.1% to 7.0%, n = 4,130; HbA1c 7.1% to 8.0%, n = 2,609; HbA1c >8.0%, n = 3,388). Patients with both low (HbA1c ≤5.5%) and high (HbA1c >8.0%) levels displayed an increased risk for MACE compared with those with values between 6.1% and 7.0%. Excess risk was driven primarily by higher rates of all-cause death among those with low HbA1c levels, while higher values were strongly associated with greater MI risk. Patterns of risk were unchanged among patients with serial HbA1c levels and persisted after multivariate adjustment. CONCLUSIONS: Among patients undergoing PCI, pre-procedural HbA1c levels display a U-shaped association with 1-year MACE risk, a pattern that reflects greater risk for death in the presence of low HbA1c (≤5.5%) and higher risk for MI with higher values (>8.0%).

One-year outcomes of patients undergoing complex percutaneous coronary intervention with three contemporary drug-eluting stents.

OBJECTIVES: We aimed to evaluate the 1-year outcomes of three everolimus-eluting stents (EES) for complex percutaneous coronary intervention (PCI). BACKGROUND: It is controversial whether contemporary bioresorbable-polymer drug-eluting stents (BP-DES) are associated with better outcomes compared with durable-polymer DES (DP-DES). METHODS: Patients undergoing PCI with cobalt-chromium (CoCr)-DP-EES (Xience), platinum-chromium (PtCr)-DP-EES (Promus), or PtCr-BP-EES (Synergy) at one high-volume institution between 2015 and 2017 were included. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of death, myocardial infarction, and target-vessel revascularization. Associations were also examined in patients undergoing complex PCI. Multivariable analysis was conducted to adjust for baseline differences across groups. RESULTS: We included n = 5,446 patients (CoCr-DP-EES, n = 3,177; PtCr-DP-EES, n = 1,555; PtCr-BP-EES, n = 714). Patients treated with PtCr-BP-EES had higher comorbidity burden and procedural complexity. At 1 year, MACE rates were 8.9% for CoCr-DP-EES versus 8.9% for PtCr-DP-EES versus 8.6% for PtCr-BP-EES (p = .97). The incidence of definite/probable stent thrombosis (ST) was also similar (0.6 vs. 0.4 vs. 0.3%, p = .69). Complex PCI was performed in n = 2,894/5,446 (53.1%). At 1 year, MACE rates were 11.5 versus 10.7 versus 10.3%, respectively (p = .83). The incidence of definite/probable ST was also similar (0.9 vs. 0.3 vs. 0.3%, p = .22). On multivariable analysis, stent type was not an independent predictor of MACE either in the overall or in the complex PCI population. CONCLUSIONS: We observed comparable 1-year rates of MACE and definite/probable ST in patients undergoing PCI with CoCr-DP-EES, PtCr-DP-EES, and PtCr-BP-EES. Results were unchanged among patients undergoing complex PCI. Future multicenter randomized studies should confirm and extend our findings.

Cardiovascular outcomes after percutaneous coronary intervention on bifurcation lesions with moderate to severe coronary calcium: A single-center registry study.

BACKGROUND: Both target vessel calcification and target vessel bifurcation are associated with worse outcomes following percutaneous coronary intervention (PCI). Whether these entities in combination interact to influence outcomes after PCI of complex coronary disease is not known. OBJECTIVES: This study evaluated the association of target vessel bifurcation and target vessel calcification, alone and in combination, with adverse events following PCI. METHODS: Registry data from 21,165 patients who underwent PCI with drug-eluting stents (DES) between January 2009 and December 2017 were analyzed. Patients were divided into four groups according to the presence or absence of target vessel bifurcation and presence of none/mild or moderate/severe target vessel calcification on angiography. Associations between lesion groups and 1 year major adverse cardiac events (MACE) were examined using Cox regression analysis. RESULTS: At 1 year, unadjusted rates of MACE, death, myocardial infarction (MI), as well as stent thrombosis were highest in the group with both bifurcation lesion and moderate/severe calcification. After adjusting for confounders such as age, renal disease, and smoking, hazard ratios for MACE were 1.14 (95%CI 0.99-1.33) for bifurcation with none/mild calcification, 1.21 (95%CI 1.06-1.38) for no bifurcation and moderate/severe calcification, and 1.37 (95%CI 1.14-1.64) for bifurcation and moderate severe calcification, compared to patients with no bifurcation and none/mild calcification. CONCLUSIONS: The presence of a bifurcating target vessel with moderate/severe calcification is associated with a higher risk of adverse outcomes than either attribute alone. New approaches are needed to improve outcomes in this subset of patients with complex coronary artery disease.

Structural analysis and characterization of egg-envelope in the Indian freshwater murrel, Channa punctatus.

Egg-envelope, an acellular coat, surrounds the egg and is essential for vitellogenin incorporation. It also plays a pivotal role during fertilization and provides protection to the developing embryo. In the present study, scanning electron microscopy was used to elucidate the structural details of isolated egg-envelopes from the Indian freshwater murrel, Channa punctatus. Several pores and single micropyle were observed on outer surface, whereas inner layer indicated deposition of proteinaceous material. The constituent proteins of egg-envelope were further characterized by Fourier transform infrared (FT-IR) spectroscopy, and electrophoresis and mass-spectrometry (MALDI-TOF-MS/MS). The secondary structure of egg-envelope proteins showed the presence of antiparallel ß-pleated sheets and aromatic amino acids. These proteins resolved into two peptides (130 kDa and 68 kDa) under denaturing conditions, which exhibited glycoprotein nature. The peptide band with low molecular mass showed significant similarity with transmembrane protein, whereas peptide band with high molecular mass matched with choriogenin protein of other fishes. These results confirm that chorion is derived from precursor protein, Choriogenin, in murrel. Chemical composition of egg-envelope supports that chorion is responsible exchange material and chemical defence during embryogenesis.

Impact of insulin treated and non-insulin-treated diabetes compared to patients without diabetes on 1-year outcomes following contemporary PCI.

OBJECTIVE: We compared 1-year outcomes in insulin-treated diabetes mellitus (ITDM) and non-ITDM patients compared to nondiabetic (DM) patients following contemporary percutaneous coronary intervention (PCI). BACKGROUND: ITDM is associated with extensive atherosclerotic disease and worse cardiovascular prognosis compared to non-ITDM patients. METHODS: We evaluated PCI patients at a large tertiary center from 2010 to 2016, grouped according to diabetes and treatment status at baseline. One-year major adverse cardiac events (MACE) were defined as a composite of death, myocardial infarction (MI), or target vessel revascularization. Outcomes were adjusted using multivariable Cox regression methods. RESULTS: During the study period, 16,889 patients underwent PCI including 13.7% ITDM, 34.0% non-ITDM, and 52.3% non-DM patients. Patients with DM were younger, including more females and non-white patients, with higher body mass index and greater prevalence of prior revascularization and chronic kidney disease. Compared to others, ITDM patients more often presented with acute coronary syndrome, in-stent restenosis, or severe lesion calcification. There were no differences in discharge rates of dual antiplatelet therapy and statins, whereas beta-blockers were more commonly prescribed in DM patients. At 1-year, both ITDM and non-ITDM patients had greater risk of MACE compared with non-DM patients, and ITDM conferred greater adjusted risk than non-ITDM (ITDM = HR: 2.11, 95% CI [1.79,2.50]; non-ITDM = HR: 1.27, 95%CI [1.09,1.47]). CONCLUSIONS: The negative prognostic effect of DM following contemporary PCI is heightened in the presence of insulin treatment, compared to non-DM patients. Focus on secondary prevention, prescription of and adherence to optimal medical therapy is necessary for post-PCI risk reduction.

Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single-center registry.

PURPOSE: Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI). BACKGROUND: CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events. METHODS: A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year. RESULTS: Within the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1-year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p-trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP. CONCLUSIONS: The presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.

Impact of stent diameter on outcomes following percutaneous coronary intervention with second-generation drug-eluting stents: Results from a large single-center registry.

BACKGROUND: In patients treated with bare metal stents and first-generation drug-eluting stents (DES) smaller stent diameter (SD) has been associated with worse long term outcomes after percutaneous coronary intervention (PCI). Data on the impact of small SD on outcomes after PCI with second-generation DES is scarce. METHODS: Consecutive patients treated with second-generation DES between 2010 and 2016 were included in a single tertiary center. Patients were grouped according to SD: ≤2.50 mm, 2.75 ≤ 3.00 mm, 3.25 ≤ 3.50 mm, and >3.50 mm. One-year event rates were estimated using the Kaplan-Meier method and adjusted hazard ratios were generated using Cox regression analysis. The primary endpoint was major adverse cardiac events (MACE; death, myocardial infarction [MI], or target vessel revascularization [TVR]). RESULTS: Of the 17,607 patients who underwent PCI with second-generation DES, 32.6% (n = 5,741) had SD ≤2.5 mm, 39.1% (n = 6,890) had SD 2.75 ≤ 3.0 mm, 22.2% (n = 3,910) had SD 3.25 ≤ 3.5 mm, and 6.1% (n = 1,066) had SD >3.5 mm. At 1 year, MACE rates were 10.5%, 9.5%, 8.0%, and 8.0%, respectively, with increasing SD (p = .006). TVR rates decreased with increasing SD (7.2%, 5.8%, 4.7%, and 3.3%, respectively [p < .0001]) whereas rates of MI across SD groups were comparable (1.7%, 1.9%, 2.0%, and 1.5%, respectively [p = .60]). After multivariable adjustment, smaller SD remained associated with higher rates of MACE, TVR, and target lesion revascularization. CONCLUSION: In a large cohort of patients undergoing PCI with second-generation DES, smaller SD was associated with increased MACE, driven by higher rates of repeat revascularization. Further research into the optimal treatment of small coronary arteries is warranted.

Outcomes by Gender and Ethnicity After Percutaneous Coronary Intervention.

Limited data on gender differences by ethnicity after percutaneous coronary intervention (PCI) exist. In this prospective cohort study, we examined gender differences in 1-year outcomes among patients from 4 ethnic groups who underwent PCI from 2010 to 2016 at a tertiary center. The primary outcome was 1-year major adverse cardiovascular events (MACE) defined as composite of all-cause death, nonfatal myocardial infarction (MI), or target lesion revascularization. Secondary outcomes included composite of death or MI and individual components of MACE. Baseline characteristics and outcomes were compared between gender in each ethnic group. The study included 16,361 patients: 7,881 whites (26.1% women), 1,943 blacks (47.3% women), 2,621 Asians (22.6% women), and 3,916 Hispanics (39.3% women). Women were older with more co-morbidities than men. Unadjusted, women had higher incidence of 1-year MACE than men among whites and Asians but not blacks or Hispanics, which was driven by a greater incidence of death in white women and greater incidence of MI in Asian women compared with male counterparts. After adjustment, findings showed similar risk of 1-year MACE in women versus men in whites, Asians, and Hispanics (Whites: hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.16; Asians: HR 1.14, 95% CI 0.77 to 1.67; Hispanics: HR 0.97, 95% CI 0.74 to 1.27). Black women had lower risk of 1-year MACE compared with black men (HR 0.67, 95% CI 0.46 to 0.97), driven by lower risk of death or MI. In conclusion, this study suggests that risk factors account for adverse events in women after PCI.

Temporal trends, determinants, and impact of high-intensity statin prescriptions after percutaneous coronary intervention: Results from a large single-center prospective registry.

BACKGROUND: High-intensity statins (HIS) are recommended for secondary prevention following percutaneous coronary intervention (PCI). We aimed to describe temporal trends and determinants of HIS prescriptions after PCI in a usual-care setting. METHODS: All patients with age ≤75 years undergoing PCI between January 2011 and May 2016 at an urban, tertiary care center and discharged with available statin dosage data were included. HIS were defined as atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg, and simvastatin 80 mg. RESULTS: A total of 10,495 consecutive patients were included. Prevalence of HIS prescriptions nearly doubled from 36.6% in 2011 to 60.9% in 2016 (P < .001), with a stepwise increase each year after 2013. Predictors of HIS prescriptions included ST-segment elevation myocardial infarction/non-ST-segment elevation myocardial infarction (odds ratio [OR] 4.60, 95% CI 3.98-5.32, P < .001) and unstable angina (OR 1.31, 95% CI 1.19-1.45, P < .001) as index event, prior myocardial infarction (OR 1.48, 95% CI 1.34-1.65, P < .001), and co-prescription of ß-blocker (OR 1.26, 95% CI 1.12-1.43, P < .001). Conversely, statin treatment at baseline (OR 0.86, 95% CI 0.77-0.96, P = .006), Asian races (OR 0.73, 95% CI 0.65-0.83, P < .001), and older age (OR 0.90, 95% CI 0.88-0.92, P < .001) were associated with reduced HIS prescriptions. There was no significant association between HIS prescriptions and 1-year rates of death, myocardial infarction, or target-vessel revascularization (adjusted hazard ratio 0.98, 95% CI 0.84-1.15, P = .84), although there was a trend toward reduced mortality (adjusted hazard ratio 0.71, 95% CI 0.50-1.00, P = .05). CONCLUSION: Although the rate of HIS prescriptions after PCI has increased in recent years, important heterogeneity remains and should be addressed to improve practices in patients undergoing PCI.

Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions.

Aims: It remains unknown what percentage of patients treated with percutaneous coronary artery intervention (PCI) have high residual inflammatory risk (RIR). Moreover, the impact of RIR on clinical outcomes has not been established. The objective of this study is to determine the prevalence of patients with persistent high levels of inflammation after PCI and to evaluate clinical outcomes according to inflammatory response. Methods and results: This is a retrospective cohort study assessing patients undergoing PCI between 2009 and 2016 with serial inflammatory status assessment from a large, prospective, and single-centre PCI registry. Assessment of inflammation status with at least two high sensitive C-reactive protein (hsCRP) measurements at baseline and follow-up with >4 weeks apart. High RIR was defined as an hsCRP≥ 2 mg/L. Patients were divided into four groups: persistent high RIR, increased RIR (first low-, then high hsCRP), attenuated RIR (first high-, then low hsCRP), or persistent low RIR. The primary endpoint was all-cause mortality at 1 year follow-up. Occurrence of myocardial infarction (MI) was assessed as secondary outcome. Seven thousand and twenty-six patients were identified with serial hsCRP measurements (30.8% of all PCI patients). Of these patients 2654 (38%) had persistent high RIR, 719 patients (10%) had increased RIR, 1088 patients (15%) had attenuated RIR, and persistent low RIR was seen in 2565 patients (37%). All-cause mortality at 1 year was 2.6% in patients with persistent high RIR, compared with 1.0% in increased RIR, 0.3% in attenuated RIR, and 0.7% in persistent low RIR patients, P < 0.01. MI at 1 year was observed in 7.5% of persistent high RIR, compared with 6.4% in increased RIR, 4.6% in attenuated RIR, and 4.3% in persistent low RIR, P < 0.01. In an adjusted model, including accounting for diabetes mellitus, acute coronary syndrome, and baseline low-density lipoprotein, results were sustained. Conclusion: Persistent high RIR is observed frequently in patients undergoing PCI. In these patients, significantly higher all-cause mortality and MI rates are observed at 1 year follow-up. Residual inflammatory risk in patients undergoing PCI should be identified and treatment options should be further explored.

Impact of Diabetes Mellitus on Ischemic Events in Men and Women After Percutaneous Coronary Intervention.

Studies have shown worse outcome for women compared with men after percutaneous coronary intervention (PCI), especially in the presence of diabetes mellitus (DM). We aimed to investigate the risk of ischemic events after PCI in women versus men stratified by the presence or absence of DM. A total of 17,154 consecutive patients from a single-center PCI registry enrolled from January 2009 to December 2014 were categorized accordingly: female/non-DM, female/DM, male/non-DM, and male/DM. End points included death and myocardial infarction (MI) at 1 year. Of the overall population, 15% (n = 2,631) were female/non-DM, 17% (n = 2,891) were female/DM, 38% (n = 6,483) were male/non-DM, and 30% (n = 5,149) were male/DM. Within the 4 study groups, female/DM had the highest risk, whereas female/non-DM and male/DM showed similar risks and male/non-DM showed lowest risk for death (4.64% vs 3.08% vs 2.93% vs 2.31%; p-trend <0.0001 over all groups and p = 0.69 between female/non-DM and male/DM, respectively) and MI (4.15% vs 3.99% vs 3.71% vs 2.55%; p trend <0.0001 over all groups and p = 0.97 between female/non-DM and male/DM, respectively). After multivariate adjustment findings were largely unchanged suggesting highest risk for adverse events in diabetic women compared with other groups and comparable risks for death and MI in nondiabetic women compared with diabetic men. In conclusion, these findings highlight the combined influence of DM and female gender as strong determinants of post-PCI risk while also illustrating "risk equivalence" between nondiabetic women versus diabetic men.