292 research outputs found

    Heart failure: Tools for nursing and medical treatment

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    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

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    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

    Anthracyclines gels: Chemical structure and functional behaviour

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    Anthracyclines are a family of antibiotics often used in cancer chemotherapy. Daunorubicin (DA) was the first isolated from a strain of Streptomyces peucetius back in 1960 and still in use for the treatment of several malignancies together with the even more frequently used analogue Doxorubicin (DX, also called Adriamycin) and its semisynthetic derivative Epirubicyn (EPI). Despite their extremely close chemical formula (Figure 1), their properties when in solution are enormously different. In fact, whereas the increase of the ionic strength induces the formation of a gel with DX1-3, in the case of the related EPI and DA molecules what is observed are only the well-known self-association phenomena documented in the literature from decades4. Please click Additional Files below to see the full abstract

    Diacylglycerol kinase (DGK) involvement in K562 erythroleukemia cell proliferation

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    Nuclear phosphoinositide metabolism has been widely described as involved in many regulatory mechanisms including cell cycle and cell proliferation (1). Our recent studies demonstrated that an increase of nuclear Diacylglycerol (DAG) regulated the G2/M progression of erythroleukemia cells, K562 (2). As nuclear DAG can be synthesized by Phospholipases C (PLC) located in the nucleus, it can also be converted to Phosphatidic acid (PA) by a class of proteins called Diacylglycerol Kinases (DGK), which phosphorylate it utilizing ATP as a source of phosphate. PA levels in the nuclear compartments peak after G2/M progression, controlling cell cycle progression (1). We found that a particular DGK isoform, DGKa, is highly localized in the nuclear compartment of K562 cells. Then, we decided to investigate if this isozyme could be involved in cell proliferation of K562 cells, stimulating the exit from G2/M checkpoint through the production of PA in the nuclear compartment. Our data show that inhibition of DGK activity by two specific inhibitors, DI (R59022) and DII (R59949), blocks K562 cell proliferation. This effect is probably due to nuclear DGKa, indeed its modulation can affect cell proliferation too. Moreover, many cell cycle related proteins seem to be targeted by DGK activity. These evidences suggest a role for DGKa in the control of cell cycle progression acting on nuclear DAG levels and increase our knowledge about the importance of PI metabolism in the nuclei of eucaryotic cells

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

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    <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

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

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    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

    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

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    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 shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients

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    Introduction: The pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis. The P2X7 receptor (P2X7R), a plasma membrane ATP-gated ion channel, is a main activator of the NLRP3 inflammasome, of the ensuing release of inflammatory cytokines and of cell death by pyroptosis. The P2X7R has been implicated in COVID-19-dependent hyperinflammation and in the associated multiorgan damage. Shed P2X7R (sP2X7R) and shed NLRP3 (sNLRP3) have been detected in plasma and other body fluids, especially during infection and inflammation. Methods: Blood samples from 96 patients with confirmed SARS-CoV-2 infection with various degrees of disease severity were tested at the time of diagnosis at hospital admission. Standard haematological parameters and IL-6, IL-10, IL-1β, sP2X7R and sNLRP3 levels were measured, compared to reference values, statistically validated, and correlated to clinical outcome. Results: Most COVID-19 patients included in this study had lymphopenia, eosinopenia, neutrophilia, increased inflammatory and coagulation indexes, and augmented sNLRP3, IL-6 and IL-10 levels. Blood concentration of sP2X7R was also increased, and significantly positively correlated with lymphopenia, procalcitonin (PCT), IL-10, and alanine transaminase (ALT). Patients with increased sP2X7R levels at diagnosis also showed fever and respiratory symptoms, were more often transferred to Pneumology division, required mechanical ventilation, and had a higher likelihood to die during hospitalization. Conclusion: Blood sP2X7R was elevated in the early phases of COVID-19 and predicted an adverse clinical outcome. It is suggested that sP2X7R might be a useful marker of disease progression

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

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    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
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