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In this response, we address and refute the comments made by Argnani (2021) on our 1908 Messina tsunami paper (Schambach et al., 2020), regarding the poor geological constraints underpinning the numerical tsunami modeling. Earthquake mechanisms can be constructed from ‘geology’, but because ruptures are usually blind, seabed evidence may be absent. Alternatively, with small magnitude earthquakes, such as Messina 1908, the small vertical displacements may not be resolved on seismic or multibeam echosounder bathymetric records, because of the relatively low frequencies of the recording equipment. Hence, for earthquake tsunami, seismological data may be more appropriate as the basis for numerical modeling. With regard to submarine mass failure, when interpreting seismic and bathymetry data, the frequency content should again be carefully considered, because smaller features may not be resolved. Regarding the 1908 tsunami, the Mw 7.1 earthquake magnitude would not be expected to generate the recorded tsunami runups for the 5 sources we modeled, as is proved from our modeling; this would also be the case for the Barreca et al. (2021) source proposed in the discussion. Combined with any of these earthquake sources, the submarine mass failure we identified and mapped, however, in large part does. The evidence most critical to the age dating of our identified SMF, presented as too old in the discussion, is that: (i) it is at the location predicted by the inverse wave ray tracing based on tsunami arrival observations; and (ii) upon forward modeling, this tsunami mechanism generates the onland tsunami record. more...

Over recent decades, Soil Erosion by Water (WSE) has become a severe and extended issue affecting all European countries. The European Mediterranean countries are particularly prone to erosion because they are subject to prolonged dry periods followed by heavy erosive rains falling on steep slopes characterized by fragile soils. In particular, natural conditions and the human impact have made Calabria region, in southern Italy, particularly prone to intense WSE. The paper describes the methodology adopted to quantify solid transport in the Allaro river basin, located on the Ionian coast of Calabria. The methodology is divided into three phases, as follows: morphometric characterization of the river basin, identification of the available gauges and analysis of rainfall and temperature data and influence area of each gauge, and estimate of solid transport using the Gavrilovic model. This model is particularly valid for rivers such as the Calabrian ones where most of the solid transport is linked to the WSE. The methodology described in this paper is suitable to all basins with morphometric and hydrological characteristics like those Allaro and Calabrian basins. Furthermore, an improvement in the river transport estimate is important not only for the planning and management of the areas near the rivers but also for the coastal areas near the mouths. more...

This study aims to verify the effectiveness of a biodegradable PLA coating on biaxially oriented poly ethylene terephthalate (BOPET) films substrates in order to develop a biodegradable sealant layer for improving the functional properties of polyester films. In particular, this work focuses on the evaluation of different surface treated BOPET films to understand the effect of typical polyester substrate treatments on the adhesion of the PLA coating. At this purpose the film’s surface properties and topography have been characterized respectively by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and by atomic force microscopy (AFM); while their surface tension has been analyzed by contact angle tests. Furthermore, the PLA coating adhesion to different BOPET webs has been assessed by delamination tests and dynamical mechanical analysis. In addition, to evaluate the optical properties haze and transparency measures have been performed. It was found that corona treatment proves to be more effective in increasing surface energy and roughness of substrate with respect to a chemical treatment. The coating adhesion to corona treated BOPET was higher compared to the neat and the chemical treated BOPET films. Improvement in adhesion of PLA on corona treated BOPET was interpreted on the basis of surface oxidation due to the electrical discharge as showed by AFM and ATR-FTIR analyses. Indeed the increase of both contact surface and functional groups able to form hydrogen bonds and other molecular interactions, allow to a better interface interaction between the two layers. more...

Over 100 years after the event, the mechanism of the 1908 Messina tsunami remains unresolved. The up to 12 m runups observed along the coasts of Sicily and Calabria cannot be explained by the coseismic tsunami, so recent studies have proposed a dual earthquake/submarine mass failure (SMF) mechanism. Here we propose a new dual source and use it to simulate tsunami generation with a three-dimensional non-hydrostatic model, coupled to a two-dimensional fully nonlinear and dispersive model, to simulate tsunami propagation to shore. We first reanalyze observations of tsunami arrival times from eyewitnesses acquired shortly after the 1908 event, and a tsunami record at a tide gauge in Malta. Similar to earlier work, this data is used to locate the likeliest tsunami source area by inverse wave ray tracing, but accounting for frequency dispersion effects on wave celerity, uncertainty in reported arrival times, and a time delay between the EQ and SMF triggering. Analyzing the seafloor morphology in this area, we identify a new SMF at the foot of the Fiumefreddo Valley, northeast of Mount Etna. The general location is consistent with earlier studies, however our SMF is much smaller (~2 km3) than, e.g., that of Billi et al. (2008) and is a fairly rigid-block-slump, rather than a translational SMF. We model the block motion and simulate tsunami generation from a dual EQ/SMF source, and its propagation to shore, in higher resolution grids and based on more accurate bathymetry and topography than in earlier work. Runups and travel times agree well with observations, except for runups on either side of the Messina Straits north of the SMF, which are still underpredicted. In the far field, simulations reproduce well the arrival time and initial wave amplitudes at the Malta tide gauge. Our newly parameterized SMF and modeling improve tsunami runups simulated near the SMF location and south of it. However, as with all previous modeling of this event, additional sources are required to explain runups in the northern Messina Straits, which we suggest might be smaller and shallower SMFs located in this area. These will be considered in future work. Highlights • New earthquake/submarine landslide model of the Messina 1908 tsunami strongly suppoorts a dual source mechanism. • Newly identified 2 km3 submarine landslide, off of Mt Etna, is the most likely non-seismic tsunami mechanism. • Improves earlier modeling by using higher resolution topography/bathymetry and grids in state of the art models. • Numerical simulations validated by post event field surveys and, for the first time, Malta tide gauge data. • New work provides strong evidence that additional submarine landslides occurred in the northern Messina Straits. more...

The large majority of extinction curves in our own Galaxy obey to a simple relation depending on one parameter, the total-to-selective extinction coefficient, R v . Different values of R v are able to match the whole extinction curve through different environments. However, anomalous curves still exist in our own Galaxy. In this paper, we aim at analysing the behaviour of some anomalous extinction curves in order to shed light into both the properties of the dust and the physical properties of their environments. From the catalogue of Savage et al., by adding the infrared data from Two-Micron All-Sky Survey catalogue, 84 lines of sight (i.e. ≃11 per cent) have been selected which deviate at the 2σ level from the normal extinction law corresponding to their best-fitting R v value. We single out a subsample of 20 lines of sight to analyse their ultraviolet (UV) deviations, in particular, at λ= 0.22 and 0.15 μm, which correspond to the bump and the far-UV rise. The lines of sight with bump lower and far-UV rise higher than their normal extinction law are defined as type A anomalous lines, and those with bump higher and far-UV rise lower as type B anomalous lines. The results here discussed are derived from extinction curve models. A anomalous types require small-to-large grain-size ratios larger than the normal curves both for silicates and carbonaceous grains; B curves also require larger ratios for carbonaceous ones but lower ratios for silicates grains. In order to interpret these results, the environments of type A curves require low-velocity shocks in order to make effective the grain-grain collisions, which increase the number of both small silicate and carbonaceous grains. However, type B lines of sight would be characterized by relatively high-velocity shocks, implying a sputtering process which sensibly destroys small silicate grains while it produces only a partial destruction of the carbonaceous ones with the consequence of increasing the number of these smaller particles. more...

Lines of sight with E(B-V)/N(HI) considerably smaller than the average value for the solar neighbourhood have been selected from the catalogue of Diplas and Savage. In order to develop quantitative considerations, estimates of the molecular hydrogen column density were obtained using the relation of Savage et al. extended to E(B-V)>0.4 with the recent data of Rachford et al. Contrary to the prevaling opinion in the literature for lines of sight with similar behaviour, we found that only 22 per cent of our sample was characterized by both an average gas density larger than 1 cm−3 and a value of RV larger than that in the diffuse interstellar medium. By computing extinction models, we were able to fit the E(B-V)/N(HI) by changing the value of RV only for some lines of sight. For the remaining ones, a ρd/ρH ratio different from the average Galactic value must be invoked. The application of the Kramers-Kronig relation to the observed extinction curves confirmed this possibility. Moreover, attemps to fit such curves with models having grain volumes corresponding to the standard ρd/ρH ratio failed. more...

The research describes the design aspects related to the large scale physical model experiments conducted within the EU Hydralab III Integrated Infrastructure Initiative, at the Canal d’Investigaciò i Esperimentaciò Marìtima, Laboratori d’Enginyeria Marìtima at Universitat Politècnica de Catalunya, Barcelona. The aim of the experimental investigation is to enlarge the knowledge on dune erosion, overwash and breaching processes during storm surges. An innovative ‘composite’ numerical model has been adopted to reach a model test setup valid to observe dune erosion, overwash and breaching. The use of the proposed approach provides a better insight into the physical problems thereby, reducing the uncertainties in selecting the optimum wave characteristics to be reproduced in the flume for a given beach dune geometry. more...

The coating technology is a strategic solution to improve the properties of flexible packaging films. Indeed, additional functional layers are often designed and added as coating on the substrate, in order to improve the characteristic of the flexible packaging and to meet the requirements for the desired gas or vapour barrier, for adhesion and sealing, or for improving the film printability, its aesthetics and durability. Moreover, this technology allows to functionalize a polymeric substrate applying materials with different chemistry, rheology, thermal and structural characteristics. BOPET films are widely used for food packaging applications thanks to their good gas barrier and mechanical properties, high transparency and for the excellent printability. In regard to sealing performance, BOPET films show poor sealing properties so they are mostly submitted to lamination processes with polyethylene. Nevertheless, this solution compromises the PET recyclability and influences the gas permeability of the multilayer PET based structures. The aim of this work is to investigate on the effect of nanocomposite biodegradable coatings for BOPET substrates in enhancing the heat sealing strength of eco-compatible PET/PLA films. At this regards, different percentages of Cloisite C30B (0%, 2% and 4%wt/wt) have been added to PLA by solution intercalation technique and the nanocomposite biodegradable materials produced have been applied on BOPET commercial films by casting. The BOPET coated films have been characterized in order to evaluate the heat sealing strength and the mechanical, gas permeability and surface properties. The results have shown that the addition of nanoclay in PLA coating significantly enhance the hot tack properties of the PET/PLA system produced, while the oxygen and water vapour permeability are slightly increased if compared to pure BOPET films. more...

We present new measurements of the interstellar reddening parameter towards 35 O stars. The results are combined with measurements from the literature for 60 stars to study the behaviour of R V with heliocentric distance. R V is the single basic parameter which characterizes the interstellar extinction from the near-infrared to the far-UV spectral region. The absolute extinction A V , from which R V is derived, is best determined by optical and near-infrared photometry (Cardelli et al. [CITE]). We consider important the derivation of R V with the same technique in the direction of as many as possible galactic O stars. more...

Introduction Candida haemulonii is now considered to be a complex of two species and one variety : C. haemulonii , Candida duobushaemulonii and the variety Candida haemulonii var. vulnera . The correct identification (ID) of these species is clinically relevant, since resistance to azole derivatives has been reported and amphotericin B has poor in vitro activity against C. duobushaemulonii isolates. Initial evaluation using MALDI-TOF MS for the ID of the C. haemulonii complex species provided promising results, but the discrimination of C. haemulonii from the variety vulnera was problematic, and the performance of the VITEK MS remains unevaluated. Objectives Evaluation of the MALDI-TOF MS performance for the ID of C. haemulonii species ID with two platforms and its’ databases and softwares. Methods 14 C. haemulonii sensu stricto , 9 C. haemulonii var. vulnera and 10 C. duobushaemulonii from hospitals belonging to the Medical school from the University of Sao Paulo were analyzed (ID by ITS1 sequence analysis). A set of reference strains from the CBS-KNAW collection was also included : C. haemulonii CBS5149 T, C. duobushaemulonii CBS7798 T, C. duobushaemulonii CBS7799, and for specificity control, the close related species Candida pseudohaemulonii (CBS10004 and CBS12370). The isolates/strains were cultured on Sabouraud plates and incubated for 48 h at 30 °C before MALDI-TOF MS analysis. Protein extraction protocol with ethanol and formic acid 70 % was carried out according to the Bruker's recommendations. Measurements were performed on a Microflex LT and its standard database (database 3.3.1), and VITEK MS instrument equipped with both IVD and RUO (SARAMIS) databases. To differentiate C. haemulonii (target group) from the variety vulnera (control group), mass spectra analysis models were created with the ClinProTools 3.0 software (Bruker). For each model, the recognition capability (RC) and cross validation (CV) percentage was generated. For single peak analysis, the AUC of each peak for the discrimination of target group from control group was directly obtained from the ClinProTools software. For the peaks with the highest AUC, the detection performances were checked using FlexAnalysis 3.4 (Bruker Daltonics). The signal-to-noise ratios (SN) of the peaks were exported to SPSS 18.0, ROC curves were constructed, and their optimal cut-off values were determined. Results All C. haemulonii sensu stricto isolates/strain had correct species assignment by both Bruker and VITEK MS IVD databases. For the species C. duobushaemulonii, the Bruker database gave correct species ID for 75 % of the isolates/strains. VITEK MS IVD analysis misidentified all C. duobushaemulonii and C. pseudohaemulonii isolates/strains as C. haemulonii (99 % of confidence level). The VITEK MS SARAMIS was unable to give genus/species ID for all isolates/strains. Discrimination of the isolates belonging to the C. haemulonii sensu stricto and to the variety vulnera was not possible with all systems and databases. The ClinProTools models showed values of CV and RC above ≥90 % for the discrimination of target group from control group. The most discriminative peaks were 5107, 6878 and 13,750 m/z (AUC >0,9), with sensibility and specificity of 88,6 %, 80,8 %, 85,8 %, and 96,6 %, 92,9 %, 93,8 %, respectively. The SN cut-off values from the peaks 5107, 6878 and 13,750 m/z for the discrimination of the target group from the control group were 2,5, 3,9 and 6,3, respectively. more...

The large majority of extinction sight lines in our Galaxy obey a simple relation depending on one parameter, the total-to-selective extinction coefficient, Rv. Different values of Rv are able to match the whole extinction curve through different environments so characterizing normal extinction curves. In this paper more than sixty curves with large ultraviolet deviations from their best-fit one parameter curve are analyzed. These curves are fitted with dust models to shed light into the properties of the grains, the processes affecting them, and their relations with the environmental characteristics. The extinction curve models are reckoned by following recent prescriptions on grain size distributions able to describe one parameter curves for Rv values from 3.1 to 5.5. Such models, here extended down to Rv=2.0, allow us to compare the resulting properties of our deviating curves with the same as normal curves in a self-consistent framework, and thus to recover the relative trends overcoming the modeling uncertainties. Such curves represent the larger and homogeneous sample of anomalous curves studied so far with dust models. Results show that the ultraviolet deviations are driven by a larger amount of small grains than predicted for lines of sight where extinction depends on one parameter only. Moreover, the dust-to-gas ratios of anomalous curves are lower than the same values for no deviating lines of sight. Shocks and grain-grain collisions should both destroy dust grains, so reducing the amount of the dust trapped into the grains, and modify the size distribution of the dust, so increasing the small-to-large grain size ratio. Therefore, the extinction properties derived should arise along sight lines where shocks and high velocity flows perturb the physical state of the interstellar medium living their signature on the dust properties. (Abridged version), 31 pages,12 figures; accepted for publication in A&A more...

Convective heat transfer was investigated numerically for rectangular enclosures both undivided and divided in two zones by a vertical partition, and having opposite isothermal walls at different temperatures. The aspect ratio was varied from 0.1 to 16 and the Rayleigh number from 3.5 ∗ 10 3 to ∗ 10 7 (non-partitioned enclosures) and from 1.0 ∗ 10 5 to 1.6 ∗ 10 8 (partitioned enclosures). The thickness and conductivity of the partition were varied. The end wall thermal boundary conditions were adiabatic or LTP (Linear Temperature Profile). The continuity, momentum and energy equations for a 2-D laminar steady flow were solved under the Boussinesq approximation by using a finite-difference method and the SIMPLEC pressure-velocity coupling algorithm. Grid-independent results indicate that the reduction in the Nusselt number caused by a thin central partition can be predicted within a few per cent (in the range investigated) by assuming the partition to be isothermal, i.e. infinitely conducting. The finite conductivity of the partition causes a temperature distribution along its length, resulting in an increase in Nu which depends on Rayleigh number, aspect ratio and end wall thermal boundary conditions. more...

Many cardiac complications in acquired immunodeficiency syndrome (AIDS) that may be faced by emergency department (ED) physicians are due to opportunistic infections or malignancy, but they may also be associated with other aspects of human immunodeficiency virus (HIV) disease and its treatment (Table 1) [1]. The clinical expression of cardiac involvement is variable and is affected by the stage of HIV dis- HIV-associated cardiac disease Cardiac emergencies C. Fungal/yeast (Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans) Nonbacterial thrombotic endocarditis Systematic embolization (lung, brain, kidney, spleen disseminated intravascular coagulopathy) Pericardial Pericardial effusion/pericarditis Cardiac tamponade, arrhythmias, CHF (for chronic pericardial effusions) A. Infectious 1. Bacterial (Mycobacterium tuberculosis, M. avium intracellulare, Nocardia asteroides) 2. Viral (Coxsackievirus, Epstein-Barr virus, cytomegalovirus, adenovirus, herpes virus) 3. Fungal (Histoplasma capsulatum, Cryptococcus neoformans) B. Idiopathic (HIV, autoimmune) C. Uremic D. Neoplastic (Kaposi’s sarcoma, non-Hodgkin’s lymphoma) sease, the degree of immunodeficiency, and the drugs used to treat HIV disease-i.e., zidovudine and protease inhibitors (PIs) in the era of highly active antiretroviral therapy (HAART) regimens-or to treat or prevent opportunistic infections and neoplasms (e.g., pentamidine, cotrimoxazole, interferon α) [2]. more...

The prevalence of myocardial abnormalities in HIV-infected patients ranges from 25 to 75% [1]. This wide range probably reflects differences in methodology, patients’ risk factors, disease stage, and environmental factors such as drug addiction or therapeutic agents. Myocardial involvement in HIVinfected patients includes dilated cardiomyopathy, myocarditis, ischemic heart disease, and neoplastic invasion from HIV-associated malignancies (e.g., non-Hodgkin’s lymphoma or Kaposi’s sarcoma). In addition, the right ventricle can be involved as a consequence of AIDS-related pulmonary disease. more...

The atherogenic effects of some highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors (PI), may synergistically promote the acceleration of cardiovascular disease and increase the risk of death from cardiovascular events even in young HIV-infected people. Along with the endothelial dysfunction associated with visceral fat accumulation and related metabolic alterations of HIV-lipodystrophy syndrome (eg, insulin resistance), vascular injury has been associated with HIV-1 infection itself, with an autoimmune reaction to viral infection (vasculitis) and with a direct action of drugs included in HAART regimens. Clinical studies suggest that HIV-infected patients under PI-including HAART and with preexisting cardiovascular risk factors, should be considered at risk for developing coronary artery disease, and that this risk increases with the time of exposure to HAART. A careful cardiovascular screening and monitoring of HIV-infected patients receiving HAART is needed according to the most recent clinical guidelines. more...

About 14 years ago, Kim and Factor reported the first case of HIV-associated pulmonary hypertension [1]. Since then more than 131 cases have been described in the literature [2]. For this reason, HIV-associated pulmonary hypertension has been included as a definite cause of precapillary pulmonary hypertension according to the executive summary of the World Health Organization (WHO) [3]. The incidence of HIV-associated pulmonary hypertension is 1 in 200, much higher than the 1 in 200,000 found in the general population [3]. No differences have been found in the clinical, histologic, and hemodynamic features between patients with HIV-associated pulmonary hypertension and HIV-uninfected patients affected by primary pulmonary hypertension. more...

Cardiac illness related to human immunodeficiency virus (HIV) infection tends to occur late in the disease course and is therefore becoming more prevalent as therapy of the viral infection and longevity improve. Autopsy series and retrospective analyses performed before the introduction of highly active antiretroviral therapy (HAART) regimens suggest that cardiac lesions are present in 25–75% of patients with acquired immunodeficiency syndrome (AIDS) [1]. HAART regimens have significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected subjects expected. However, early data raised concerns about HAART being associated with an increase in both peripheral and coronary arterial diseases. HAART is only available to a minority of HIV-infected individuals worldwide, and studies prior to HAART therapy remain globally applicable. As 36.1 million adults and children are estimated to be living with HIV/AIDS and 5.3 million adults and children are estimated to have been newly infected with HIV during the year 2000 [2], HIV-associated symptomatic heart failure may become one of the leading causes of heart failure worldwide. A variety of potential etiologies have been postulated for HIVrelated heart disease, including myocardial infection with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, drug-related cardiotoxicity, nutritional deficiencies, and prolonged immunosuppression (Table 1). more...

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed. more...

The Authors report a rare case of intermittent left anterior hemiblock in a 86-year-old man admitted to Department of Emergency Medicine for progressive impoverishment of intellectual functions and episodes of chest pain. They present this rare case of intermittent left anterior hemiblock where the intermittence was not linked to heart rate variations preceding the beginning of the hemiblock being present on the same ECG two different QRS complexes with no modification in frequency or A-V conduction: this finding suggesting a vascular origin of the disturbance. They also stress the importance of a prompt diagnosis in a Department of Emergency Medicine. more...

A combination of interferon alpha and ribavirin has been suggested to reach a higher rate of sustained virological response in patients with chronic hepatitis C than monotherapy. In this study we assessed the long-term efficacy of this combination therapy in the treatment of selected Italian naive chronic hepatitis C patients compared to interferon alpha monotherapy.We enrolled 428 naive patients who were randomly assigned to receive either recombinant interferon alpha-2b and ribavirin for 24 weeks or interferon alpha-2b alone for 48 weeks. The primary end-point of the study was the rate of sustained virological response. Serum HCV RNA levels were determined before treatment; during treatment at weeks 12 and 24 in the patients receiving the combination therapy; at weeks 12, 24, 36 and 48 in the patients receiving monotherapy; and after therapy at weeks 12, 24 and 48 in the patients in both study groups.Sustained virological response was observed in 43% of the patients treated with combination therapy and in 14% of the patients treated with monotherapy. Logistic regression analysis showed that sustained response was associated with the combination therapy, with HCV genotype other than 1b, with an HCV viral load of 3x10(6) copies/ml or less, with an inflammation score of 7 or less, and with an estimated duration of disease of 10 years or less.A 24-week treatment course with interferon alpha-2b and ribavirin offers a greater chance of sustained virological response compared to treatment with interferon alpha-2b alone for 48 weeks, and may be indicated as initial therapy in such patients. more...

The purpose of this study is to underline how topical is the chapter of the sequelae of pulmonary tuberculosis and to try to make a classification. Pulmonary tuberculosis can be cured definitely or hesitate in disease (BK negative) that is totally independent from tuberculosis about their pathogenesis and clinical features. They are called sequelae.We made a statistical analysis that investigate a group of 110 patients without active infection (BK negative) admitted in the hospital because of a sequela of pulmonary tuberculosis. Patients were treated in the past by collapse-therapy or by antibiotic-therapy until their spittle became negative for BK.A significant (p0.05) relationship between each kind of sequela, among the most important ones (fibrothorax, interstitial fibrosis, bronchiectasis, empyema with or without pleural fistula, parafibrotic emphysema), and type of treatment, results.The sequelae of tuberculosis of the lung are highly disadvantageous for people who are affected; are observed frequently; are closely dependent on what kind of treatment the patient has received; are classified in iatrogenic, not iatrogenic or mixed. more...

Increased levels of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) have been reported in patients with dilated cardiomyopathy. We investigated the myocardial expression of TNF-alpha and iNOS in patients with HIV-associated cardiomyopathy (HIV-DCM) compared with patients with idiopathic dilated cardiomyopathy (IDCM).Endomyocardial biopsy specimens from 82 HIV-DCM and 80 IDCM patients were processed for determination of the immunostaining intensity of TNF-alpha and iNOS and for virological examination. Negative controls were derived from autopsy myocardium specimens from 32 HIV-negative patients without known heart disease. The mortality rate for congestive heart failure between groups according to the intensity of iNOS staining was also evaluated. The mean intensity of both TNF-alpha and iNOS staining was greater in patients with HIV-DCM (0.81 and 1.007, respectively) than in patients with IDCM (0.44 and 0.49, respectively) and controls (0.025 and 0.027, respectively). The staining intensity of both TNF-alpha and iNOS was inversely correlated with CD4 count. The staining intensity of iNOS was greater in HIV-DCM patients with HIV/coxsackievirus B3 (CVB3) or with HIV/cytomegalovirus coinfection than in IDCM patients showing infection with CVB3 and adenovirus alone. The staining intensity of iNOS correlated to mortality rate, because it was higher in HIV-DCM patients and, in particular, in those with an optical density unit1.Cytokine activation seems to play a significant pathogenetic role in both HIV-DCM and IDCM. In HIV-DCM patients, the state of immunodeficiency may favor the selection of viral variants of increased pathogenicity, influencing the clinical course of cardiomyopathy by enhancement of the inflammatory process. more...

Human immunodeficiency virus (HIV) infection is increasingly recognized as an important cause of dilated cardiomyopathy. However, the pathogenesis of the heart-muscle disease in the acquired immunodeficiency syndrome is unclear.We performed a prospective, long-term clinical and echocardiographic follow-up study of 952 asymptomatic HIV-positive patients to assess the incidence of dilated cardiomyopathy and to analyze the clinical variables associated with the development of cardiomyopathy. All patients with an echocardiographic diagnosis of dilated cardiomyopathy underwent endomyocardial biopsy for histologic, immunohistologic, and virologic assessment.During a mean (+/-SD) follow-up period of 60+/-5.3 months, an echocardiographic diagnosis of dilated cardiomyopathy was made in 76 patients (8 percent), with a mean annual incidence rate of 15.9 cases per 1000 patients. The incidence of dilated cardiomyopathy was higher in patients with a CD4 count of less than 400 cells per cubic millimeter (as compared with a CD4 count ofor =400 cells per cubic millimeter) and in those who received therapy with zidovudine. A histologic diagnosis of myocarditis was made in 63 of the patients with dilated cardiomyopathy (83 percent). Inflammatory infiltrates were predominantly composed of CD3 and CD8 lymphocytes, with staining for major histocompatibility complex class I antigens in 71 percent of the patients. In the myocytes of 58 patients, HIV nucleic acid sequences were detected by in situ hybridization, and active myocarditis was documented in 36 of the 58. Among these 36 patients, 6 were also infected with coxsackievirus group B (17 percent), 2 with cytomegalovirus (6 percent), and 1 with Epstein-Barr virus (3 percent).Dilated cardiomyopathy may be related either to a direct action of HIV on the myocardial tissue or to an autoimmune process induced by HIV, possibly in association with other cardiotropic viruses. more...

The heart is frequently involved in the acquired immunodeficiency syndrome (AIDS). This study was planned to assess the prevalence of cardiac involvement in a large and selected population of patients who died of AIDS. Of 440 AIDS patients who underwent autopsy, cardiac involvement was documented in 82 patients. Dilated cardiomyopathy was found in 12 patients; lymphocytic interstitial myocarditis was documented in 30 patients, and in 10 of 12 patients with dilated cardiomyopathy. Inflammatory infiltrate was predominantly composed by CD3+ and CD8+ with a positive staining for major histocompatibility class I in 70% of the cases. Infective endocarditis was documented in 28 patients, pericardial effusion in 53 patients, myocardial Kaposi's sarcoma in 2 patients, myocardial B-cell immunoblastic lymphoma in 1 patient. Sequences of human immunodeficiency virus (HIV) nucleic acid were detected using the technique of in situ hybridization in the myocytes of 29 autopsy patients and in 25 of 29 patients with a positive hybridization signal an active myocarditis was documented. Among them, 7 presented a coinfection with Coxsakievirus group B, 2 with Epstein-Barr virus, and 1 with cytomegalovirus. HIV-associated cardiomyopathy may be related either to a direct action of HIV on the myocardial tissue or to an autoimmune process induced by HIV even in association with other cardiotropic viruses. more...

Clinical-pathological studies have demonstrated that in 46-51% of AIDS patients a lymphocytic interstitial myocarditis can be found at autopsy. In80% of these patients no specific etiologic factor for myocarditis was found. This pathological finding is believed to be related to a specific pathogenetic action of HIV on myocardial tissue and it is called HIV-related myocarditis (HRM). In 15-30% of patients with lymphocytic interstitial myocarditis ventricular arrhythmias have been described. In order to assess the prevalence and the predictive value of ventricular ectopic beats (VEB) in the diagnosis of HRM, we performed a retrospective analysis of 24-hour Holter recordings, M-mode and two-dimensional echocardiographic and Doppler parameters and post-mortem myocardial histopathological and virologic findings on a selected sample of 35 NYHA functional class II patients died of AIDS. The patients were divided into two groups according to post-mortem histopathological findings of myocardium specimens: Group 1 (n = 19) including patients with histopathological findings consistent with diagnosis of HRM; Group 2 (n = 16), including patients without histopathological findings of myocarditis. Group 2 patients represented the control group. The retrospective analysis demonstrated a greater prevalence of VEB class IV and subclass IVb in Group 1 compared to Group 2 (p = 0.009 and p = 0.004, respectively). The other classes of VEB did not present a statistically significant difference between groups. VEB class IV presented a 81.2% diagnostic predictive value (subclass IVa: 50%; subclass IVb: 90.9%). Ejection fraction, kinetic score and Doppler E/A ratio, Ei Area, Ai Area and Ai Area/total Area ratio and isovolumetric relaxation time were significantly correlated to Lown's classes of VEB (p0.001) and to the values of CD+ cells (p0.001); on the other hand, VEB classes correlated significantly with the values of CD+ cells (p0.001). Syncytial cells and HIV p24 antigen in cultured myocytes were detected in 17 Group 1 patients (89.4%) and in 2 Group 2 patients (12.5%; p0.001). These results have demonstrated that in selected cases of AIDS patients specific classes of VEB may represent a simple and sensitive electrocardiographic marker of HRM. VEB classes correlate significantly with systolic and diastolic echocardiographic parameters and to the values of CD4+ cells. Furthermore, in patients with HRM a direct pathogenetic action of HIV may be assumed. more...

Reduced glutathione (GSH) is decreased in patients affected by chronic hepatitis C (CHC) as well as in patients who are HIV positive. Because the liver is the most important source of plasmatic GSH, we measured the concentrations of GSH in the liver (H-GSH) of patients with CHC who were either HIV positive or negative, correlating it to the concentrations of GSH in plasma (P-GSH) and in peripheral blood mononuclear cells (PBMCs) (L-GSH), to the replication activity of hepatitis C virus (HCV) in PBMCs, to the activity of the liver disease, and to the state of immunodeficiency in patients who were HIV positive.One hundred, five patients with serologically and histologically demonstrated CHC (55 HIV positive and 50 HIV negative) entered the trial. Fifty-one healthy individuals made up a control group for P-GSH and L-GSH concentrations. H-GSH concentration was determined by high performance liquid chromatography on liver specimens obtained by ultrasound-guided biopsy according to the method described by Reed et al. The concentrations of P-GSH and L-GSH were determined according to the method described by Suarez et al. The detection of HCV RNA strands in PBMCs was performed according to the method described by Qian et al. Histological findings and degree of fibrosis were scored according to the numerical scoring system proposed by Scheuer and by Knodell et al.H-GSH, P-GSH, and L-GSH were significantly reduced in patients affected by CHC compared with healthy controls (p0.001). H-GSH and particularly L-GSH were more significantly reduced in patients who were HIV positive compared with those who were HIV negative (p0.001), without significant correlation with the values of the T cell subset CD4+. The reductions in H-GSH, P-GSH, and L-GSH were significantly correlated to the replication activity of HCV in PBMCs (p0.001) and to the grade of activity of the liver disease assessed by the values of ALT (p0.001) and by histological and fibrosis scores of CHC (p0.001). In both groups of patients with CHC, H-GSH, P-GSH, and L-GSH were more reduced in patients addicted to drugs than in patients who were not addicted.In patients with CHC, particularly those who are HIV positive, a systemic depletion of GSH is present. This depletion may be a factor underlying the resistance to interferon therapy and, in patients who are HIV positive, to antiretroviral drugs, fostering HCV and/or HIV replication. This may represent the biological basis for GSH replacement therapy. more...

Human immunodeficiency virus (HIV) possesses an intrinsic cardiopathogenic action that may be detected even in the early stages of HIV disease. To assess an early impairment of systolic and diastolic function in asymptomatic HIV-positive patients (CD4+or = 600/mm3), we performed a multicenter echocardiographic and echo-Doppler trial on 1236 asymptomatic NYHA class I HIV-positive patients (885 M and 351 F; mean age 28 years) compared with 1230 healthy subjects (922 M and 308 F; mean age 30 years). The sample size was established considering, as null hypothesis, a difference less than 10% in the values of the principal echocardiographic and echo-Doppler parameters between groups with a 90% statistical power (alpha = 0.01; beta = 0.10). Analysis of echocardiographic and echo-Doppler data revealed a reduction of 19.7% in ejection fraction, an increase of 55.7% in wall motion score, a reduction of 34.6% in the E/A ratio, and an increase of 19.7% in the isovolumetric relaxation time in HIV-positive subjects compared with healthy controls (p0.001). Baseline electrocardiographic alterations were observed in 707 (57.2%) HIV-positive subjects and in 169 (13.7%) of the subjects of the control group (p0.001). The results of our study have demonstrated that in asymptomatic HIV-positive subjects a significant impairment of systolic and diastolic function may be detected by echocardiographic and echo-Doppler examination, confirming an early involvement of the heart in HIV disease. more...

The aim of this study was to assess the role and therapeutic efficacy of two azole antifungal drugs, fluconazole and itraconazole, in the treatment of endoscopically-diagnosed Candida oesophagitis in patients with Acquired Immunodeficiency Syndrome (AIDS). The study considered 120 Human Immunodeficiency Virus (HIV)-positive patients (67 males and 53 females, mean age 27 +/- 5) at their first episode of oesophageal candidiasis diagnosed by endoscopy (Kodsi's grade II endoscopic classification). The patients were double-blindly randomized into 2 groups of 60 patients each according to the pharmacological therapy administered: a) the patients in the first group received fluconazole (100 mg b.i.d. per os); b) the patients in the second group received itraconazole (100 mg b.i.d. per os). In order to evaluate the efficacy of the pharmacological therapy, a clinical examination was performed every week up to the end of the follow-up period (2 months); endoscopic examination was performed at the end of pharmacological treatment (3 weeks). All patients selected for the study gave their informed consent. Complete remission of endoscopic lesions was observed in 45 patients (75%) in the fluconazole group and in 23 patients (38%) in the itraconazole group (p0.001); partial remission of endoscopic lesions was observed in 15 patients (25%) in the fluconazole group and in 28 patients (47%) in the itraconazole group (p0.05). No response was observed in 9 patients (15%) in the itraconazole group. Complete clinical remission was observed in 47 patients (78%) in the fluconazole group and in 44 patients (73%) in the itraconazole group (p = n.s.); partial clinical remission was observed in 13 patients (22%) in the fluconazole group and in 12 patients (20%) in the itraconazole group (p =- m.s.). No clinical response was observed in 4 patients (7%) in the itraconazole group. No side-effects worthy of note were observed in the patients of either treatment group. The results of this study demonstrated that fluconazole is associated with higher rates of endoscopic and clinical cure than itraconazole, with a statistically significant difference as regards endoscopic cure. Both drugs appear to be safe and well tolerated. Nevertheless, further controlled clinical investigations are needed to improve our knowledge of the therapeutic action of antifungal drugs in the treatment of Candida oesophagitis in HIV disease. more...

The “Butcher-Oemler” effect was originally defined as the excess of blue galaxies observed in distant rich clusters when compared to local counterparts. Subsequent observations revealed that a larger fraction of objects in clusters between 0.1 more...

One hundred and twenty-two patients suffering from slight or moderate essential arterial hypertension with a previous history of myocardial infarction were selected for inclusion in this study. Patients were divided into two groups of 61 according to the type of anti-hypertensive therapy received. Patients in group 1 received nifedipine (30 mg p.d.), while patients in group 2 were treated using other anti-hypertensive therapy (diuretics, alpha-methyldopa, clonidine, indapamide). At the end of the follow-up period, which lasted 5 years, a statistically significant improvement in the following factors was observed in group 1 in comparison to the control group: (a) an improved response of both SBP (p less than 0.001) and DBP (p less than 0.001) levels to anti-hypertensive therapy; (b) a more significant diminution in the thickness of the interventricular septum (p less than 0.001) and the posterior wall of the left ventricle (p less than 0.001) assessed using ultrasonography; (c) a reduced number of cases of post-infarction angina (p less than 0.05); (d) fewer cases of recurrent infarction (p less than 0.05); (e) fewer deaths as a result of re-infarction (p less than 0.01). These results confirm that the vascular and cardioprotective effects of nifedipine give a good long-term outcome in hypertensive patients with a previous history of myocardial infarction. more...

One hundred and twenty-two patients suffering from slight or moderate essential arterial hypertension with a previous history of myocardial infarction were selected for inclusion in this study. Patients were divided into two groups of 61 according to the type of anti-hypertensive therapy received. Patients in Group 1 received nifedipine (30 mg p.d.), while patients in Group 2 were treated using other anti-hypertensive therapy (diuretics, alpha-methyldopa, clonidine, indapamide). At the end of the follow-up period, which lasted 5 years, a statistically significant improvement in the following factors was observed in Group 1 in comparison to the control group: (a) an improved response of both SBP (p less than 0.001) and DBP (p less than 0.001) levels to anti-hypertensive therapy; (b) a more significant diminution in the thickness of the interventricular septum (p less than 0.001) and the posterior wall of the left ventricle (p less than 0.001) assessed using ultrasonography; (c) a reduced number of cases of post-infarction angina (p less than 0.05); (d) fewer cases of recurrent infarction (p less than 0.05); (e) fewer deaths as a result of re-infarction (p less than 0.01). These results confirm that the vascular and cardioprotective effects of nifedipine give a good long-term outcome in hypertensive patients with a previous history of myocardial infarction. more...

We have solved the radiative transfer equation taking into account both absorption and scattering into the line of sight to the observer to model the disc of spiral galaxies.A dust model has been adopted, suitable for the diffuse interstellar medium of our Galaxy, to obtain, in aU the considered spectral range (1000 ÷ 10000 Å), consistent quantities to describe both the absorption and the scattering properties of the dust. more...

A significant evolution has been detected in intermediate redshift clusters (z < 0.9), first by photometric studies ([1], [2]), which showed an excess of blue objects; subsequent spectroscopic studies revealed anomalies in most of the galaxies, mainly consisting of excessively strong Balmer lines. In order to explain the spectroscopic observations, bursts of star formation superimposed to the traditional scenario of galactic evolution are needed. The analysis of spectral lines and colours by means of an evolutionary synthesis model ([3]), including both the stellar contribution and the emission of the ionized gas, allows in most of the cases the determination of the time elapsed since the end of the burst and the fraction of galactic mass involved in it. In the clusters considered (AC103, AC114, AC118 at z = 0.31, [4]), the theoretical analysis demonstrates that the bursts affect substantial galactic mass fractions, typically 30 % or more. The observations can be equally well reproduced by either elliptical+burst models or by spiral+burst models in which the star formation is truncated at the end of the burst. The analysis of an UV colour such as (1550-V) is proposed as a valid method to distinguish between the two cases for Hδ strong red galaxies. more...

The “Butcher–Oemler” effect was originally defined as the excess of blue galaxies observed in distant rich clusters when compared to local counterparts. Subsequent observations revealed that a larger fraction of objects in clusters between 0.1 < z < 1 show signs in their spectra of the presence of young stars, i.e. of a recent (during the last 2 Gyrs) or current burst of star formation. more...

UV and visual spectral energy distributions of young generations have been synthesized from evolutionary tracks in the HR diagram and model atmospheres. The influence of several parameters has also been analyzed. Their UV portions have been checked with the UV spectra of 24 clusters of the LMC obtained by Cassatella et al. (1987). The models generally agree well with the observations and make it possible to derive ages for various assumed abundances. Ages thus derived have been compared, in an age-age diagram, with those obtained from the integrated UBV photometry. While there are no systematic differences between these two age determinations, a fraction of clusters displays a large scatter, larger than what is expected from the observational errors alone. Possible causes for this scatter are briefly analyzed. 31 refs. more...