Absence of protein A expression is associated with higher capsule production in staphylococcal isolates

Staphylococcus aureus is a major human pathogen, and a leading cause of soft tissue and blood stream infections. One of the causes of its success as a pathogen is the peculiar array of immune evasion factors through which the bacterium avoids host defenses, where the staphylococcal protein A (SpA) plays a major role thanks to its IgG binding activities. Moreover, SpA has recently been proposed as a promising vaccine antigen. In this study, we evaluated the expression of SpA in a collection of staphylococcal strains, about 7% of which did not express SpA (SpA- strains), despite the presence of the gene. By a comparative genomic analysis, we identified that a mutation in the spa 5′ UTR sequence affecting the RBS is responsible for the loss of SpA in a subset of SpA- strains. Using a high-throughput qRT-PCR approach on a selected panel of virulence-related genes, we identified that the SpA- phenotype is associated with lower spa transcript levels and increased expression and production of capsule as well as other changes in the transcription of several key virulence factors. Our data suggest that the SpA- phenotype has occurred in geographically distinct strains through different molecular mechanisms including both mutation, leading likely to translation alterations, and transcriptional deregulation. Furthermore, we provide evidence that SpA- strains are highly susceptible to phagocytic uptake mediated by anti-capsule antibodies. These data suggest that S. aureus may alter its virulence factor expression pattern as an adaptation to the host or environment. Vaccination strategies targeting both SpA and capsule could therefore result in broader coverage against staphylococcal isolates than SpA alone

LINEE GUIDA CLINICHE PER LA PREVENZIONE DELLA CARDIOPATIA ISCHEMICA NELLA IPERCOLESTEROLEMIA FAMILIARE Una patologia sotto-diagnosticata e sotto-trattata

AIMS. Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD) due to lifelong elevated plasma low-density lipoprotein (LDL) cholesterol levels. This paper aims to describe the problem of FH underdiagnosis and undertreatment and to promote CHD prevention providing recommendations for the screening and treatment of patients with FH. Methods and results. In many countries, less then 1% of FH patients are diagnosed, although the estimated prevalence of this condition is about 1/500 for heterozygous FH and the results of FH screening in a general population of Northern Europe suggest a prevalence of 1/200. Studies on FH patients agree on a widespread failure to achieve recommended target of LDL-cholesterol and on a 12-fold increased CHD risk. With a theoretical prevalence between 1/500 and 1/200, it is estimated that 14 to 34 million subjects worldwide have FH. With evidence of plasma cholesterol ≥8 mmol/L (≥310 mg/dL) in an adult or ≥6 mmol/L (≥230 mg/dL) in a child, premature CHD, tendon xanthomas, or sudden premature cardiac death, we recommend the screening for FH of this subject and of all first-degree relatives. The treatment of a patient with diagnosis of FH should have LDL targets of <3.5 mmol/L (<135 mg/ dL) for children, <2.5 mmol/L (<100 mg/dL) for adults, and <1.8 mmol/L (<70 mg/dL) for adults with known CHD or diabetes. Beside life-style and dietary modifications, first line therapies are statins, ezetimibe, and bile acid binding resins in children, and maximal potent statin dose, ezetimibe, bile acid binding resins, and fibrates in adults. Homozygotes FH and in treatment-resistant heterozygotes FH with CHD should be referred for LDL-apheresis. Conclusion. Familial hypercholesterolemia is a common condition that carries a high risk of CHD. The underdiagnosis and undertreatment of FH require a focused intervention that implements the screening and promote the early and aggressive treatment of these patients

Adherence to Antihypertensive Medications andCardiovascular Morbidity Among Newly DiagnosedHypertensive Patients

Background—Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Methods and Results—Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18 806 newly diagnosed hypertensive patients 35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories— high (proportion of days covered, 80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, 40%)—and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P0.032). Conclusions—The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits

The CRACK programme: a scientific alliance for bridging healthcare research and public health policies in Italy

Healthcare utilisation databases, and other secondary data sources, have been used with growing frequency to assess health outcomes and healthcare interventions worldwide. Their increased popularity as a research tool is due to their timely availability, the large patient populations covered, low cost, and applicability for studying real-world clinical practice. Despite the need to measure Italian National Health Service performance both at regional and national levels, the wealth of good quality electronic data and the high standards of scientific research in this field, healthcare research and public health policies seem to progress along orthogonal dimensions in Italy. The main barriers to the development of evidence-based public health include the lack of understanding of evidence-based methodologies by policy makers, and of involvement of researchers in the policy process. The CRACK programme was launched by some academics from the Lombardy Region. By extensively using electronically stored data, epidemiologists, biostatisticians, pharmacologists and clinicians applied methods and evidence to several issues of healthcare research. The CRACK programme was based on their intention to remove barriers that thwart the process of bridging methods and findings from scientific journals to public health practice. This paper briefly describes aim, articulation and management of the CRACK programme, and discusses why it might find articulated application in Italy

Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment

In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved.Peer Reviewe