In Vivo Suppression of Precore mRNA Synthesis Is Associated with Mutations in the Hepatitis B Virus Core Promoter

AbstractWe have examined the in vivo effect of hepatitis B virus (HBV) core promoter mutations on the expression of precore mRNA and pregenomic RNA transcripts in the liver of 24 patients with chronic HBV infection, applying a novel transcript-specific RT-PCR assay. The double A1762T/G1764A mutation in the basic core promoter was detected in 11 cases. This mutation was in all cases associated with absence or low levels of precore mRNA transcripts without significantly affecting the levels of total core promoter-directed transcription in the liver of infected patients. Precore mRNA synthesis was suppressed by the A1762T/G1764A mutation regardless of the presence of the precore stop codon mutation G1896A, suggesting that in addition to downregulating an immunomodulatory protein this double basic core promoter mutation may also confer a replication advantage to the virus. Additional mutations detected in the core promoter may also contribute to the observed changes in precore mRNA levels. Our in vivo study shows therefore that the double A1762T/G1764A mutation is associated with the specific suppression of precore mRNA synthesis directed by the HBV core promoter

How to misuse echo contrast

<p>Abstract</p> <p>Background</p> <p>Primary intracardiac tumours are rare, there are however several entities that can mimic tumours. Contrast echocardiography has been suggested to aid the differentiation of various suspected masses. We present a case where transthoracic echocardiography completely misdiagnosed a left atrial mass, partly due to use of echo contrast.</p> <p>Case presentation</p> <p>An 80 year-old woman was referred for transthoracic echocardiography because of one-month duration of worsening of dyspnoea. Transthoracic echocardiography displayed a large echodense mass in the left atrium. Intravenous injection of contrast (SonoVue, Bracco Inc., It) indicated contrast-enhancement of the structure, suggesting tumour. Transesophageal echocardiography revealed, however, a completely normal finding in the left atrium. Subsequent gastroscopy examination showed a hiatal hernia.</p> <p>Conclusion</p> <p>It is noteworthy that the transthoracic echocardiographic exam completely misdiagnosed what seemed like a left atrial mass, which in part was an effect of the use of echo contrast. This example highlights that liberal use of transoesophageal echocardiography is often warranted if optimal display of cardiac structures is desired.</p

Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review

Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data. We performed a systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterize the distribution of disease, and they have been compared with a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis

Pegylated Interferon and Ribavirin Dosing Strategies to Enhance Sustained Virologic Response

Hepatitis C virus (HCV) affects about 170 million people worldwide and is the most common chronic blood borne infection in the United States. Since the advent of blood screening protocols in the early 1990s, injection drug use has become the leading cause of infection. Hepatitis C can have both hepatic and nonhepatic manifestations of infection. Hepatic manifestations include hepatic fibrosis, cirrhosis, liver cancer, and liver failure. The standard treatment for chronic HCV is combination therapy with pegylated interferon-α and ribavirin. Although pegylated interferon and ribavirin has been used against HCV for close to a decade, advances in therapy have centered on doses and treatment durations. There has been increasing interest in applying on-treatment response or viral kinetics to predict antiviral response rates and shape therapeutic intervention. Protease inhibitors are a promising adjuvant to combination therapy, but their efficacy and safety are still under investigation

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013

2019 ESC/EAS Guidelines for themanagement of dyslipidaemias: lipid modification to reduce cardiovascular risk

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