Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure

OBJECTIVES: To investigate the effects of aldosterone receptor blockade in postinfarction heart failure. METHODS: Eighty-seven rats with moderate myocardial infarction were randomized to receive either no drug or canrenone, the active metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a combination of the two drugs. Treatment was initiated 1 month after coronary ligation and lasted 4 weeks. Echocardiography was performed at baseline and after 4 weeks. LV catheterization, isolated heart studies, morphometric histology, myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the treatment period. RESULTS: Infarct sizes were 33+/-3, 32+/-3, 34+/-3, and 34+/-4% in the placebo, canrenone, ramipril, and combination groups, respectively. Canrenone attenuated LV remodeling, improved LV systolic and diastolic function, and markedly reduced interstitial and perivascular fibrosis. These effects were increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine content was decreased while ventricular fibrillation threshold significantly augmented by canrenone. SERCA-2 levels remained unchanged. CONCLUSIONS: Canrenone attenuated LV dilation and interstitial remodeling, and improved LV filling dynamics and systolic function in the rat model of postinfarction heart failure. Addition of ramipril conferred further cardioprotection. Canrenone also reduced myocardial norepinephrine content and increased ventricular fibrillation threshold. The data provide a potential explanation for the decreased sudden death observed in the RALES study.The mechanisms of action of aldosterone inhibition are still poorly understood, despite its proven efficacy in heart failure. Rats with postinfarction heart failure were randomized to receive for 1 month either no drug or canrenone, or ramipril, or a combination of canrenone and ramipril. Canrenone treatment was associated with a significant attenuation of LV dilation, better LV diastolic and systolic dynamics, and a marked reduction of reactive fibrosis. These effects were enhanced by concomitant ramipril therapy. Moreover, canrenone increased ventricular fibrillation threshold and reduced myocardial norepinephrine content. The data may explain the reduced mortality demonstrated by the RALES.     

Radiation therapy in indolent primary cutaneous B cell lymphoma: a single institute experience

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p?=?0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p?=?0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.     

Melanoma: Diagnosis,Staging, and Treatment. Consensus group recommendations

The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.     

Newspaper coverage of HIV/AIDS in China from 2000 to 2010

Mass media in China play a significant role in the dissemination of HIV/AIDS knowledge to the general public. Previous studies have described how the Chinese mass media portray HIV/AIDS in general, but no study has yet to examine changes in patterns of HIV/AIDS reporting over time. This study aims to describe and examine newspaper coverage of HIV/AIDS in China from 2000 to 2010. A systematic search of the China Core Newspapers Database was conducted to identify HIV/AIDS-focused news articles; we found 3648 articles. Results show that coverage rates of HIV/AIDS in newspapers remained low, with only about three articles published per newspaper per year between 2000 and 2010. The sources focused primarily on prevention methods (23.7%), development of a cure or vaccine (21.2%), and education and awareness (17.2%). The HIV/AIDS-related topic covered in an article varied significantly depending on scope (national vs. local) of the newspaper (χ²=130.37, p<0.001) and article type (χ²=455.72, p<0.001). Totally, more articles were classified as positive than negative from 2002 to 2010. Findings indicate that the HIV/AIDS news-reporting pattern has shifted in the past decade, with more news stories disclosing information about prevention or treatment. However, coverage of HIV/AIDS remains insufficient. Enhancing collaboration between health educators and media sources can be an important strategy in disseminating HIV/AIDS knowledge.     

Control of Dielectric and Mechanical Properties of Styrenic Block Copolymer by Graphite Incorporation

The structure–property relationship of dielectric elastomers, as well as the methods of improving the control of this relationship, has been widely studied over the last few years, including in some of our previous works. In this paper, we study the control, improvement, and correlation, for a significant range of temperatures, of the mechanical and dielectric properties of polystyrene-b-(ethylene-co-butylene)-b-styrene (SEBS) and maleic-anhydride-grafted SEBS (SEBS-MA) by using graphite (G) as filler in various concentrations. The aim is to analyze the suitability of these composites for converting electrical energy into mechanical energy or vice versa. The dielectric spectroscopy analysis performed in the frequency range of 10 to 1 MHz and at temperatures between 27 and 77 °C emphasized an exponential increase in real permittivity with G concentration, a low level of dielectric losses (≈10⁻³), as well as the stability of dielectric losses with temperature for high G content. These results correlate well with the increase in mechanical stiffness with an increase in G content for both SEBS/G and SEBS-MA/G composites. The activation energies for the dielectric relaxation processes detected in SEBS/G and SEBS-MA/G composites were also determined and discussed in connection with the mechanical, thermal, and structural properties resulting from thermogravimetric analysis, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses.     

Public views on the Covid‐19 immunity certificate: A scoping review

IntroductionAlready in its first implementation, the introduction of the Covid‐19 immunity certificate has generated some debate among the public. This debate might be a hindrance to the effective realization of this policy. This study aimed to systematically review published research evaluating public feeling of the Covid‐19 immunity certificate policy measure and to find which factors might influence its acceptance.MethodsWe followed the scoping review methods manual by the Joanna Briggs Institute. We included studies with no time limits that presented novel data, and no exclusions have been made based on study design. We excluded articles that presented just expert opinions.ResultsWe found and reviewed 17 articles. The included studies were conducted in two main countries (the United Kingdom and Switzerland), with the rest from Israel, Italy, Spain, Germany, Australia, Taiwan and China. Both qualitative and quantitative studies were included, and nonrepresentative samples were mostly used to explore the public feeling about the Covid‐19 immunity certification. The included studies showed that public views on immunity certification are quite contradictory and influenced by age, gender, ethnicity, political orientation and attitudes towards Covid‐19 vaccination. The topic more often addressed by the included studies was the public''s views on the positive and negative implications of the Covid‐19 immunity certificate in terms of ethical, legal and behavioural consequences of this measure.ConclusionThe varying acceptance rates are notable and may partly be linked to differences in demographics, Covid‐19 concerns and ideological beliefs, as seen in other health‐related tracking policies. Moreover, dominant factors behind the (un)success of this policy are complex and entangled with the cultural and political dimensions rather than being just technical. For this reason, it is important to expand psychosocial research to better understand the concerns behind health certifications and allow planning of culturally based and ethically sound suitable strategies. This would be very relevant to increasing public approval and compliance with this public health measure.Patient or Public ContributionThis does not apply to our work as it was a review paper.     

Extracellular vesicles mediate the communication between multiple myeloma and bone marrow microenvironment in a NOTCH dependent way

Multiple myeloma (MM) is an incurable hematologic neoplasm, whose poor prognosis is deeply affected by the propensity of tumor cells to localize in the bone marrow (BM) and induce the protumorigenic activity of normal BM cells, leading to events associated with tumor progression, including tumor angiogenesis, osteoclastogenesis, and the spread of osteolytic bone lesions. The interplay between MM cells and the BM niche does not only rely on direct cell-cell interaction, but a crucial role is also played by MM-derived extracellular vesicles (MM-EV). Here, we demonstrated that the oncogenic NOTCH receptors are part of MM-EV cargo and play a key role in EV protumorigenic ability. We used in vitro and in vivo models to investigate the role of EV-derived NOTCH2 in stimulating the protumorigenic behavior of endothelial cells and osteoclast progenitors. Importantly, MM-EV can transfer NOTCH2 between distant cells and increase NOTCH signaling in target cells. MM-EV stimulation increases endothelial cell angiogenic ability and osteoclast differentiation in a NOTCH2-dependent way. Indeed, interfering with NOTCH2 expression in MM cells may decrease the amount of NOTCH2 also in MM-EV and affect their angiogenic and osteoclastogenic potential. Finally, we demonstrated that the pharmacologic blockade of NOTCH activation by γ-secretase inhibitors may hamper the biological effect of EV derived by MM cell lines and by the BM of MM patients. These results provide the first evidence that targeting the NOTCH pathway may be a valid therapeutic strategy to hamper the protumorigenic role of EV in MM as well as other tumors.