Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design.

Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.

Determinants of left ventricular hypertrophy in patients with recent diagnosis of essential hypertension.

Objective: Development of left ventricular hypertrophy (LVH) is a multifactorial phenomenon. We retrospectively assessed the risk factors for LVH in patients with recent diagnosis of essential hypertension.

Methods: We analysed 1518 participants with recent diagnosis of essential hypertension (≤2 years).

Vascular endothelial growth factor blockade prevents the beneficial effects of β-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure.

Background: Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, β-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart.

Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA <50 copies/ml and immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline.

β1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy.

Background: The sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G-protein-coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein-coupled receptor kinase-2, which triggers desensitization and downregulation processes.

Molecular aspects of the cardioprotective effect of exercise in the elderly.

Aging is a well-recognized risk factor for several different forms of cardiovascular disease. However, mechanisms by which aging exerts its negative effect on outcome have been only partially clarified. Numerous evidence indicate that aging is associated with alterations of several mechanisms whose integrity confers protective action on the heart and vasculature.

Genetic test for dilated and hypertrophic cardiomyopathies: useful or less than useful for patients?

Genetic testing for potentially heritable cardiomyopathies has advanced from basic scientific discovery to clinical application. Nowadays, genetic diagnostic tests for cardiomyopathies are clinically available. As a consequence is fundamental the understanding of the clinical utility, in terms of diagnosis and prognosis, of genetic test results.

Toxicological effects induced by the nanomaterials fullerene and nanosilver in the polychaeta Laeonereis acuta (Nereididae) and in the bacteria communities living at their surface.

Fullerene (nC60) and nanosilver (nAg) are nanomaterials with bactericide properties. The increments in their use raise questions about their potential environmental impacts, including estuarine ones. The polychaete Laeonereis acuta (Nereididae) secretes mucus that is colonized by bacteria communities.

Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy.

Background: Visceral Leishmaniasis (VL) is endemic in 88 countries, in areas of relatively low incidence with a relevant proportion of immune suppressed patients clinical presentation, diagnosis and management may present difficulties and pitfalls.

Methods: Demographic data, clinical, laboratory features and therapeutic findings were recorded in patients identified by a regional VL disease registry from January 2007 to December 2010.

Results: A total of 55 patients (36 adults mean age 48.

Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure.

Background: Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels.

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways.

Fanconi anaemia (FA) is a genetic cancer predisposition disorder associated with cytogenetic instability, bone marrow failure and a pleiotropic cellular phenotype, including low thresholds of responses to oxidative stress, cross-linking agents and selected cytokines. This study was aimed at defining the scope of abnormalities in gene expression using the publicly available FA Transcriptome Consortium (FTC) database (Gene Expression Omnibus, 2009 and publicly available as GSE16334). We evaluated the data set that included transcriptomal analyses on RNA obtained from low-density bone marrow cells (BMC) from 20 patients with FA and 11 healthy volunteers, by seeking to identify changes in expression of over 22,000 genes, including a set of genes involved in: (i) bioenergetic pathways; (ii) antioxidant activities; (iii) response to stress and metal-chelating proteins; (iv) inflammation-related cytokines and (v) DNA repair.

Advocacy practices among U. S. pediatric dentists.

Purpose: Advocacy is the primary mission of the American Academy of Pediatric Dentistry (AAPD), but members' participation in advocacy is not well known. The purpose of this study was to examine advocacy by AAPD members and their attitudes toward various advocacy-related activities.

Methods: An Internet-based questionnaire, e-mailed to 4,328 AAPD members via Survey Monkey, consisted of 19 questions on: demography; advocacy training; attitudes toward advocacy; and past, recent, and current advocacy practices.

Access to treatment for HBV infection and its consistency with 2008 European guidelines in a multicentre cross-sectional study of HIV/HBV co-infected patients in Italy.

Background: A survey was performed in 2008 to evaluate the profiles of patients with chronic hepatitis B cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes: i) factors associated with access to the anti-HBV treatment in a cohort of HIV/HBV co-infected patients cared for in tertiary centers of a developed country with comprehensive coverage under the National Health System (NHS); ii) consistency of current anti-HBV regimens with specific European guidelines in force at the time of the study and factors associated with the receipt of sub-optimal regimens.

Methods: The study focuses on 374 (87.

Impact of diabetes on cardiac sympathetic innervation in patients with heart failure: a 123I meta-iodobenzylguanidine (123I MIBG) scintigraphic study.

Objective: Impaired parasympathetic and sympathetic nervous system activity have been demonstrated in patients with diabetes mellitus (DM) and correlated with worse prognosis. Few data are available on the effect of DM on cardiac neuropathy in heart failure (HF). The aim of the current study was to assess cardiac sympathetic activity in HF patients with and without DM.

From clinical description, to in vitro and animal studies, and backward to patients: oxidative stress and mitochondrial dysfunction in Fanconi anemia.

Fanconi anemia (FA) is a rare genetic disease associated with deficiencies in DNA repair pathways. A body of literature points to a pro-oxidant state in FA patients, along with evidence for oxidative stress (OS) in the FA phenotype reported by in vitro, molecular, and animal studies. A highlight arises from the detection of mitochondrial dysfunction (MDF) in FA cell lines of complementation groups A, C, D2, and G.

[Audit system on quality of breast cancer diagnosis and treatment: results of quality indicators on screen-detected lesions in Italy, 2010].

This survey, conducted by the Italian breast screening network (GISMa), collects yearly individual data on diagnosis and treatment on about 50% of all screen-detected, operated lesions in Italy. The 2010 results show good overall quality and an improving trend over time. Critical issues were identified, including waiting times and compliance with the recommendations on not performing frozen section examination on small lesions.

Oral anticoagulation therapy in heart failure patients in sinus rhythm: a systematic review and meta-analysis.

Background: Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated.

Methodology And Principal Findings: We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm.

β-adrenergic receptors and G protein-coupled receptor kinase-2 in Alzheimer's disease: a new paradigm for prognosis and therapy?

Alzheimer's disease (AD) is a devastating form of dementia that imposes a severe burden on health systems and society. Although several aspects of AD pathogenesis have been elucidated over the last few decades, many questions still need to be addressed. In fact, currently available medications only provide symptomatic improvement in patients with AD without affecting disease progression.

Sjøgren's syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials.

An involvement of oxidative stress (OS) was found in recent studies of Sjøgren's syndrome (SS) that reported significant changes in protein oxidation, myeloperoxidase activity, TNF-α, nitrotyrosine, and GSH levels in plasma from SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl-lysine, were reported in saliva from SS patients. Previous reports concurred with a role of OS in SS pathogenesis, by showing a decreased expression of antioxidant activities in conjunctival epithelial cells of SS patients and in parotid gland tissue samples from SS patients.

Instruments for geriatric assessment: new multidimensional assessment approaches.

During the last century the considerable increase in life expectancy has led to important demographic changes and, consequently, to new clinical scenarios. Nowadays, chronic conditions, comorbidities and socio-economic factors constitute a relevant health management issue. In particular, the definition of frail elderly individuals has proven to have a strong role in the identification of high-risk patients, their clinical management and prognosis.

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management.

Fanconi anaemia (FA) is a genetic disease featuring bone marrow failure, proneness to malignancies, and chromosomal instability. A line of studies has related FA to oxidative stress (OS). This review attempts to evaluate the evidence for FA-associated redox abnormalities in the literature from 1981 to 2010.

Blockade of β-adrenoceptors restores the GRK2-mediated adrenal α(2) -adrenoceptor-catecholamine production axis in heart failure.

Background And Purpose: Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of β-adrenoceptor antagonist (β-blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. β-Blockers have been shown to reduce SNS hyperactivity in HF, but the underlying molecular mechanisms are not understood.

[From bench to bedside: new insights into the treatment of heart failure].

Despite significant advances in pharmacological and clinical treatment, heart failure remains a leading cause of morbidity and mortality worldwide. G-protein coupled receptors are a wide superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Since heart failure is characterized by the overactivity of different neurohormones, such as catecholamines and angiotensin II, responsible for several detrimental effects on the cardiovascular system, over the last decade therapeutic strategies targeting beta-adrenergic and angiotensin receptors have been developed.