Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS1 16-42 antigen

Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116–42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116–42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines.publishedVersio

Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS116-42 antigen

Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116–42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116–42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines

ERGONOMIC CONCEPTS IN DENTAL MEDICINE

Dental medicine is an extremely complex medical field, comprising several specialties (orthodontics and dentofacial orthopedics, prosthodontics, dental surgery, endodontics etc.), which in most cases also require the assistance of a dental nurse. Purpose. In this paper, we have tried to present a number of very interesting ergonomic aspects in the dental office, which aim at simplifying work at this level. Material and method. This study was conducted between May and July 2018 using a questionaire applied to a number of 69 dental practitioners from Bucharest. Results and discussions. Results obtained in this study give us an image about how current dental practitioners understand ergonomics in daily practice. Conlclusions. All the aspects discussed in this study have an important role in the ergonomy of daily activity of a dental office. More important is that the majority of dentists involved in the stuty understand and apply the ergonomic concepts underlined by this study

Ischemic Heart Disease in the Context of Different Comorbidities

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide [...

The Professional and Psycho-Emotional Impact of the COVID-19 Pandemic on Medical Care—A Romanian GPs’ Perspective

The aim of this study was to assess the psycho-emotional impact and the adjustment degree of Romanian general practitioners (GPs) in the coronavirus disease 2019 (COVID-19) pandemic context. With a cross-sectional design, the study included 677 GPs to whom a validated questionnaire based on different items targeting three factors was sent: burden of prevention, presence of stress symptoms, and adjustment to pandemic. The burden of prevention and the adjustment effort to the pandemic were felt significantly more by female doctors and by GPs working in associated offices. The case definition quality, the support received, the professional life changes, and the stress symptoms proved to be the main predictors for the adjustment to pandemic. The adjustment measurement questionnaire can be used in further studies to identify the most supportive public health practices in difficult epidemiological contexts

Pharmacological Targets in Chronic Heart Failure with Reduced Ejection Fraction

Heart failure management has been repeatedly reviewed over time. This strategy has resulted in improved quality of life, especially in patients with heart failure with reduced ejection fraction (HFrEF). It is for this reason that new mechanisms involved in the development and progression of heart failure, along with specific therapies, have been identified. This review focuses on the most recent guidelines of therapeutic interventions, trials that explore novel therapies, and also new molecules that could improve prognosis of different HFrEF phenotypes

Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function

Comparable Efficacy in Ischemic and Non-Ischemic ICD Recipients for the Primary Prevention of Sudden Cardiac Death

(1) Background: In patients suffering from heart failure, the main causes of death are either hemodynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extent from these devices. (2) Methods: The primary outcome of this single-center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients—symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death—were included retrospectively: 59% ischemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP) patients. Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not significantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 patients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95% confidence interval (CI) 0.45 to 2.28; p = 0.97). All-cause mortality occurred in 14 of 166 patients (8.4%) in the NICMP group and 18 of 237 patients (7.6%) in the ICMP group. Sudden cardiac death occurred in two patients (1.2%) in the NICMP group and in four patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; p = 0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusions: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovascular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies

The Cardiovascular Effects of Cocoa Polyphenols—An Overview

Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%–65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health