A combined approach to assess the potential coverage of a multicomponent protein-based vaccine

Meningococcal disease caused by Neisseria meningitidis sero- group B is a public health concern even in developed countries. Despite glycoconjugate vaccines against the other invasive sero- groups (A, C, W135, Y) are already available and successfully introduced in many countries, no vaccine is currently in use for prevention of serogroup B meningitis. A protein based, multicomponent vaccine (4CMenB) has been developed and proposed for prevention of invasive serogroup B meningococcal disease (MenB). This novel vaccine has been tested in clinical trials and shown to be well tolerated and immunogenic, inducing bactericidal antibodies in infants, adolescents and adults. The high level of genetic and antigenic variability observed in MenB clinical isolates, requires a suitable method to assess the ability of the 4CMenB vaccine to cover genetically diverse menig- ococcal strains and to estimate the potential public health impact. To this purpose the Meningococcal Antigen Typing System (MATS) has been developed and recently described. This method provides a quick and reproducible tool to estimate the level of expression and immunoreactivity of each of the vaccine antigens, in any meningococcal isolate, and it is related to the likelihood that the isolate will be killed by sera from immunized subjects. A multi-laboratory study involving several European countries, demonstrates that the 4CMenB has the potential to protect against a significant proportion of menB strains circulating in Europe. The full article is free available on www.jpmh.or

Heart failure: Tools for nursing and medical treatment

Background: To validate a structured interview designed to evaluate the healthcare and information needs of patients with heart failure (HF), who were also characterized by means of the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 36-item Short-Form Health Survey (SF-36). Methods: Forty-five in- and outpatients with HF were administered a structured interview concerning their information and healthcare needs (together with the KCCQ and SF-36) with the aim of investigating the effects of healthcare models on their quality of life (QoL). Twenty- -one patients were also involved in a one-week test-retest validity study carried out in order to verify reproducibility and stability by means of concordance and K statistics. Results: The reproducibility of the structured interview was good or very good for all items, with a mean Kw of 0.59; the clarity and acceptability of most of the questions were good. Positive judgements of hospital care inversely related to the patients’ New York Heart Association class. The subjects about which the patients sought greater information were diet, sleep, therapies and physical exercise, with cardiologists and general practitioners (GPs) being more involved than nurses. The most frequently discussed subject was diagnostic examinations. The questionnaire scores of our patients were generally lower than those reported in the literature, possibly because of their advanced age. However, it is difficult to believe that the quality of care was extraneous to their generally worse health-related QoL. Conclusions: Our HF patients experienced a ‘basic’ healthcare model (hospitals, GPs, cardiologists) and judged them acceptable. Their ability to think critically about care was increasingly compromised as HF progressed and their health-related QoL decreased. (Cardiol J 2011; 18, 4: 411–420

Well-Being and Perceived Quality of Life in Elderly People Displaced After the Earthquake in L’Aquila, Italy

On 6 April 2009, the city of L’Aquila was hit by a violent earthquake that destroyed almost all of its medieval centre, and the surviving inhabitants were evacuated and relocated in temporary quarters or undamaged homes. The aim of this study was to investigate the perceived quality of life of the elderly population 3 years after the earthquake in relation to the social and logistic issues of new housing. The study was carried out between October 2011 and March 2012, and involved 571 subjects aged over 65 years living in the municipality of L’Aquila. The interviews took place in the surgeries of general practitioners and the city’s Department of Prevention and Vaccination in the anti-influenza immunisation period. The instrument used was a 36-item questionnaire with closed, multiple choice answers divided into the following sections: demographics, everyday activities, health and perceived health, and the quality of life in the city. The results show that, 3 years after the earthquake, the elderly population living in the new towns and temporary housing of L’Aquila have a worse perception of their quality of life than the others. They feel a certain social isolation and wish to live elsewhere. Governments faced with the problems arising from a natural calamity should take into account all of the elements making up a good quality of life and, before making choices whose impact cannot be changed, consider both their immediate and long-term social consequences

Sex Disparity in Response to Hepatitis B Vaccine Related to the Age of Vaccination

Hepatitis B virus (HBV) infection is one of the major infectious hazards for health-care workers (HCWs) because of the frequency of percutaneous exposures to blood or body fluids. For this reason, all HCWs should be vaccinated, including students in medicine and health professional degree programs. The aim of this study was to assess the immune coverage to anti-HBV vaccine and long-lasting protective titres of anti-HBs antibodies in female and male students to evaluate gender-related differences in response to HBV vaccination. Data relative to anti-HBs antibody titre, sex, age, and age at vaccination were collected and analyzed from 5291 Italian students (1812 males and 3479 females) of the graduate courses at the School of Medicine, who underwent the mandatory health surveillance of workers exposed to biological risk. The results indicated that gender affects the immune response to HBV vaccine, particularly evident in the case of females vaccinated after one year of age who exhibited a statistically significant (p = 0.0023) 1.21-fold increase in median antibody titre with respect to males. Our findings could contribute to the optimization of HBV vaccination schedules in health surveillance of HCWs

A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process

<p>Abstract</p> <p>Background</p> <p>The E1 protein of Hepatitis C Virus (HCV) can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP), and a C-terminal domain (CT) comprising two segments, a pre-anchor and a trans-membrane (TM) region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1.</p> <p>Results</p> <p>Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis.</p> <p>The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA). This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT region of E1, reducing the fusion process <it>in vitro</it>, strongly reduced the amount of cross-recurrence further supporting interaction between this region and FP.</p> <p>Conclusion</p> <p>Our results support a fusion model for HCV in which the FP and the C-terminal region of E1 are juxtaposed and interact in the post-fusion structure. These findings have general implications for viruses, as any visualization of the post-fusion FP-TM complex has been precluded by the impossibility to obtain crystallised viral fusion proteins containing the trans-membrane region. This limitation gives to sequence based modelling efforts a crucial role in the sketching of a molecular interpretation of the fusion process. Moreover, our data also have a more general relevance for cell biology as the mechanism of intracellular fusion showed remarkable similarities with viral fusion</p

Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

Background: Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM. Methods: Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions. Results: sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20-6.33] for ≥ 32.0 ng/mL and 2.00 [1.02-3.94] for 16.5-32.0 ng/mL compared to &lt; 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90-4.55] for ≥ 337 ng/L and 1.48 [1.05-2.10] for 89-337 ng/L compared to &lt; 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01-2.62]). A 'cardiac score' based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19-1.53], C-statistic = 0.739) and development of CV events. Conclusions: sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

none10noopenSabbatinelli, Jacopo; Castiglione, Stefania; Macrì, Federica; Giuliani, Angelica; Ramini, Deborah; Vinci, Maria Cristina; Tortato, Elena; Bonfigli, Anna Rita; Olivieri, Fabiola; Raucci, AngelaSabbatinelli, Jacopo; Castiglione, Stefania; Macrì, Federica; Giuliani, Angelica; Ramini, Deborah; Vinci, Maria Cristina; Tortato, Elena; Bonfigli, Anna Rita; Olivieri, Fabiola; Raucci, Angel

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

none12noDisorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene-a microRNA previously linked to CVD-to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.openGiuliani, Angelica; Montesanto, Alberto; Matacchione, Giulia; Graciotti, Laura; Ramini, Deborah; Protic, Olga; Galeazzi, Roberta; Antonicelli, Roberto; Tortato, Elena; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Olivieri, FabiolaGiuliani, Angelica; Montesanto, Alberto; Matacchione, Giulia; Graciotti, Laura; Ramini, Deborah; Protic, Olga; Galeazzi, Roberta; Antonicelli, Roberto; Tortato, Elena; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Olivieri, Fabiol

Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia

Background: Nutraceutical combinations (NCs) against hypercholesterolemia are increasing in the marketplace. However, the availability of NCs without monacolin K is scarce even though the statin-intolerant population needs it. Methods: This study is a parallel-group, randomized, placebo-controlled, double-blind trial. We evaluated the effects of the NC containing phytosterols, bergamot, olive fruits, and vitamin K2 on lipid profile and inflammatory biomarkers in 118 subjects (mean age ± SD, 57.9 ± 8.8 years; 49 men and 69 women) with hypercholesterolemia (mean total cholesterol ± SD, 227.4 ± 20.8 mg/dL) without clinical history of cardiovascular diseases. At baseline and 6 and 12 weeks of treatment, we evaluated lipid profile (total, LDL and HDL cholesterol, and triglycerides), safety (liver, kidney, and muscle parameters), and inflammatory biomarkers such as hs-CRP, leukocytes, interleukin-32, and interleukin-38 and inflammatory-microRNAs (miRs) miR-21, miR-126, and miR-146a. Results: Compared to the placebo, at 6 and 12 weeks, NC did not significantly reduce total cholesterol (p = 0.083), LDL cholesterol (p = 0.150), and triglycerides (p = 0.822). No changes were found in hs-CRP (p = 0.179), interleukin-32 (p = 0.587), interleukin-38 (p = 0.930), miR-21 (p = 0.275), miR-126 (p = 0.718), miR-146a (p = 0.206), myoglobin (p = 0.164), and creatine kinase (p = 0.376). Among the two reported, only one adverse event was probably related to the nutraceutical treatment. Conclusions: The evaluated nutraceutical combination did not change serum lipid profile and inflammatory parameters, at least not with the daily dose applied in the present study

The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence

K.L.S. was supported by the Australian National Health and Medical Research Council (NHMRC) C. J. Martin Fellowship and Career Development Fellowship. A.F.H. was supported by a Marie Curie Fellowship (PIEF-GA-2012-328377). F.O., L.F., and S.B. were recipients of Novartis fellowships from the Ph.D. program of the University of Siena (Siena, Italy) and University of Bologna (Bologna, Italy), respectively.GNA2091 is one of the components of the 4-component meningococcal serogroup B vaccine (4CMenB) vaccine and is highly conserved in all meningococcal strains. However, its functional role has not been fully characterized. Here we show that nmb2091 is part of an operon and is cotranscribed with the nmb2089, nmb2090, and nmb2092 adjacent genes, and a similar but reduced operon arrangement is conserved in many other gram-negative bacteria. Deletion of the nmb2091 gene causes an aggregative phenotype with a mild defect in cell separation; differences in the outer membrane composition and phospholipid profile, in particular in the phosphoethanolamine levels; an increased level of outer membrane vesicles; and deregulation of the zinc-responsive genes such as znuD. Finally, the Δ2091 strain is attenuated with respect to the wild-type strain in competitive index experiments in the infant rat model of meningococcal infection. Altogether these data suggest that GNA2091 plays important roles in outer membrane architecture, biogenesis, homeostasis, and in meningococcal survival in vivo, and amodel for its role is discussed. These findings highlight the importance of GNA2091 as a vaccine component.PostprintPeer reviewe