PSPC1 Binds to HCV IRES and Prevents Ribosomal Protein S5 Binding, Inhibiting Viral RNA Translation.

Hepatitis C virus (HCV) infects the human liver, and its chronic infection is one of the major causes of Hepatocellular carcinoma. Translation of HCV RNA is mediated by an Internal Ribosome Entry Site (IRES) element located in the 5'UTR of viral RNA. Several RNA Binding proteins of the host interact with the HCV IRES and modulate its function. Here, we demonstrate that PSPC1 (Paraspeckle Component 1), an essential paraspeckle component, upon HCV infection is relocalized and interacts with HCV IRES to prevent viral RNA translation. Competition UV-crosslinking experiments showed that PSPC1 interacts explicitly with the SLIV region of the HCV IRES, which is known to play a vital role in ribosomal loading to the HCV IRES via interaction with Ribosomal protein S5 (RPS5). Partial silencing of PSPC1 increased viral RNA translation and, consequently, HCV replication, suggesting a negative regulation by PSPC1. Interestingly, the silencing of PSPC1 protein leads to an increased interaction of RPS5 at the SLIV region, leading to an overall increase in the viral RNA in polysomes. Overall, our results showed how the host counters viral infection by relocalizing nuclear protein to the cytoplasm as a survival strategy.

Society for Cardiovascular Magnetic Resonance 2022 Cases of SCMR case series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2022 digital collection of cases are presented in this manuscript.

Transfemoral aortic valve replacement in a nonagenarian with aortic stenosis and cardiac amyloidosis: case report.

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.

Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Ranolazine: Multifaceted Role beyond Coronary Artery Disease, a Recent Perspective.

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.

Biomarkers after risk stratification in acute chest pain (from the BRIC Study).

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.

Inflammatory bowel disease: perioperative pharmacological considerations.

The perioperative management of patients with inflammatory bowel disease is challenging given the altered immune system that results from a variety of biologic and immunomodulator therapies. Clinicians are often faced with challenges and complicated equations when deciding on the type and dose of medication. To understand the effect of these medications and review the evidence regarding the management of these medications in the perioperative setting, a PubMed-based literature search (January 1, 1960, through April 1, 2011) was conducted using the following search terms: perioperative management, risk, outcome, inflammatory bowel disease, ulcerative colitis, Crohn's disease, aminosalicylates, glucocorticoids, purine analogues, cyclosporine, methotrexate, biologic therapy, infliximab, and thromboembolism. The 414 articles identified were manually sorted to exclude those that did not address perioperative risk, outcomes, and medications in the abstracts, yielding 84 articles for review. Additional references were obtained from the citations within the retrieved articles. This review surveys the findings of the selected articles and presents guidelines and resources for perioperative medication management for patients with inflammatory bowel disease undergoing surgery.

Antimicrobial efficacy of fruit extracts of two piper species against selected bacterial and oral fungal pathogens

Aim: To assess the antimicrobial efficacy of five solvent extracts of two Piper species commonly used in diet and traditional medicine, P. cubeba and P. longum, against selected bacterial and oral fungal pathogens i.e. Streptococcus mutans, Staphylococcus aureus, Candida albicans and Saccharomyces cerevisiae. Methods: The antimicrobial activity of five extracts of cubeb berries and Indian long pepper fruits was determined by the agar well diffusion method. The minimum inhibitory concentration (MIC) for the acetonic, methanolic and ethanolic extracts was determined by the modified agar well diffusion method. Results: Of the 5 fruit extracts evaluated, acetone, ethanol and methanol extracts of both the Piper spp. were found to have variable antimicrobial activities against all the four oral pathogens. The acetonic fruit extract of P. cubeba was the most effective against both the yeasts with the highest zone of inhibition (15.31 mm) against C. albicans followed by the methanolic (12.31 mm) and ethanolic (11.94 mm) extracts. C. albicans was found to be most sensitive pathogen, which survived up to 6.25 mg/mL in the acetonic extract (MIC = 12.5 mg/mL) followed by the methanolic and ethanolic extracts (MIC = 25 mg/mL). The acetonic, methanolic and ethanolic extracts of P. longum fruits showed almost equal inhibition zones of both yeasts, ranging between 10.64 and 14 mm. C. albicans survived up to 12.5 mg/mL (MIC= 25 mg/mL) while S.cerevisiae survived up to 25 mg/mL (MIC = 50 mg/mL). Conclusions: The crude extracts obtained from the fruits of the two Piper spp. may be used to treat oral fungal species, especially C. albicans, as they produced larger inhibition zones than antifungal drugs often used to treat these pathogens.

Discontinuation of antiplatelet therapy prior to low-risk noncardiac surgery in patients with drug-eluting stents: a retrospective cohort study.

BACKGROUND: Drug-eluting coronary stents (DESs) pose a challenge in the perioperative period. Sirolimus and paclitaxel may inhibit reendothelialization of the traumatized vessel, making it vulnerable to platelet-mediated thrombosis. Given the anecdotal evidence and case series suggesting that DESs may be more vulnerable to thrombosis on discontinuation of antiplatelet agents than are bare-metal stents, we sought to quantify this risk. METHODS: We linked the Cleveland Clinic Heart Center database with the Cleveland Clinic Internal Medicine Preoperative Assessment Consultation and Treatment (IMPACT) Center database to identify all patients who had undergone DES placement at the Cleveland Clinic and subsequently were evaluated for noncardiac surgery between July 2003 and July 2005. Outcome measures included 30-day rate of postoperative myocardial infarction (MI), DES thrombosis, major bleeding, and all-cause mortality. RESULTS: We identified 114 patients who underwent noncardiac surgery a median of 236 days (IQR 125-354) after stent placement. Forty-five patients (40%) underwent surgery within 180 days of stenting, 15 of whom (13%) underwent surgery within 90 days of stenting. Eighty-eight patients (77%) discontinued all antiplatelet agents a median of 10 days before surgery. No patients died. Two patients (1.8%, 95% CI 0.5%-6.2%) suffered postoperative MIs, but postoperative catheterization showed neither had DES thrombosis (0%, 95% CI 0%-3.3%). One patient developed major bleeding (0.9%, CI 0.2%-4.8%). CONCLUSIONS: These data suggest that the overall risk of stent thrombosis is low in low-risk noncardiac surgery patients with DESs, particularly those who have undergone at least 180 days of antiplatelet therapy, even after complete discontinuation of antiplatelet agents.