Disease trends over time and CD4+CCR5+ T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus.

BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. METHODS AND RESULTS: Clinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 ± 9 years; 14.4 ± 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4+CCR5+; CD4+CXCR3+; CD4+HLADR+; CD4+CD45RA+RO-, CD4+CD45RO+RA- and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4+CCR5+ T cells were independently associated with the development of carotid atherosclerosis in SLE patients. CONCLUSION: Serial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression.

AN INTERNATIONAL COOPERATION BY USING AN ALL-ENCOMPASSING PASSIVE RADON MONITOR.

The recently developed radon film-badge makes it possible to measure radon indoors, in soil, in water and/or in aqueous media (e.g. mud). As a result of its wide response linearity, this monitor has been successfully used to measure radon in-water with concentrations from 10 to ~10 000 Bq/L. By exploiting the unique characteristics of this badge, a mini-survey has been carried out by Health Canada in which radon in water was measured from 12 private wells, as well as in tap water originating from the Ottawa River. Due to the widespread interest of different laboratories in using these passive monitors, laboratories were provided with plastic films to construct their own badges by using in-house CR-39 detectors. Monitors were then irradiated by a known radon concentration at the National Institute of Radiation Metrology (ENEA)'s radon chamber and sent back to each laboratory for processing and counting. Even though these laboratories have been using different etching- and counting-procedures, the film-badge responses varied only within ~12%.

Implementation of GOLD consensus report in real life: results from the Velletri-Lariano (VELA) cohort.

BACKGROUND: COPD is one of the leading causes of morbidity and mortality. Pharmacotherapy improves quality of life and reduces exacerbations although low adherence with prescribed treatments may represent a barrier to optimal disease management. The first objective of this paper is to report the distribution of COPD patients according to GOLD categories, in a sample of patients from a cohort study in an area of the Latium region in Italy. The second objective is to evaluate the agreement between the distributions of severity obtained from the HCPs and the experts included in the study board (Board). METHODS: COPD patients were given a card to collect demographic and clinical data at baseline. Information in those cards was independently evaluated by HCPs and Board to include each patient into one of the four GOLD categories. RESULTS: In a sample of 187 stable COPD patients, 59% male, mean age 70 year, the distribution of GOLD categories according to the Board was: 6% A, 34% B, 2% C, and 58% D. A discrepancy in GOLD classification was observed between the study board and field-based HCPs, regarding more than 50% of the patients, with a clear trend to underestimate the frequency of patients in D level (21%) and to overestimate the frequency in C level (21%). CONCLUSIONS: These results describe for the first time the distribution of COPD patients in an Italian cohort according to the GOLD categories, with the highest frequencies in levels B and D. The misclassification from HCPs may impact the therapeutic approach and the clinical outcomes.

Asthma management among allergists in Italy: results from a survey.

BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS AND OBJECTIVES: The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management. METHODS: An anonymous 16 item web questionnaire was available (April-October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy. RESULTS: One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence. CONCLUSIONS: Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

The role of T and B cells in human atherosclerosis and atherothrombosis.

Far from being merely a passive cholesterol accumulation within the arterial wall, the development of atherosclerosis is currently known to imply both inflammation and immune effector mechanisms. Adaptive immunity has been implicated in the process of disease initiation and progression interwined with traditional cardiovascular risk factors. Although the body of knowledge regarding the correlation between atherosclerosis and immunity in humans is growing rapidly, a relevant proportion of it derives from studies carried out in animal models of cardiovascular disease (CVD). However, while the mouse is a well-suited model, the results obtained therein are not fully transferrable to the human setting due to intrinsic genomic and environmental differences. In the present review, we will discuss mainly human findings, obtained either by examination of post-mortem and surgical atherosclerotic material or through the analysis of the immunological profile of peripheral blood cells. In particular, we will discuss the findings supporting a pro-atherogenic role of T cell subsets, such as effector memory T cells or the potential protective function of regulatory T cells. Recent studies suggest that traditional T cell-driven B2 cell responses appear to be atherogenic, while innate B1 cells appear to exert a protective action through the secretion of naturally occurring antibodies. The insights into the immune pathogenesis of atherosclerosis can provide new targets in the quest for novel therapeutic targets to abate CVD morbidity and mortality.

Asthma management among different specialists: results from a national Italian survey.

In Europe more than 50% of asthmatic treated patients have a not well-controlled asthma. The present survey aims at investigating how different specialists approach asthmatic patients. A web anonymous questionnaire was randomly administered to 604 General Practitioners (GPs), 241 Pneumologists and 131 Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk factors, treatment and future risk. A general agreement emerges about asthma diagnostic work-up. All categories are aware of the impact of comorbidities on asthma. LABA/inhaled steroids combination is considered the first choice treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA) alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely on inflammation biomarkers, whereas reduction of rescue medication is more relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more than 50% of all physicians and is not known by most of GPs. Adherence is considered a crucial problem in asthma management. All categories seem to have a good knowledge about asthma. The cultural background may account for mild differences in asthma control tools and treatment options. GPs have a pivotal role in discriminating patients who need specific assessment by specialists. It is thus important that GPs and specialists share common tools for recognizing and managing those patients.

A simple approach to measure the radon equilibrium factor F from air filter gross beta counting.

The internal alpha dose assessment (ICRP 65, 1994) depends on the value of the equilibrium factor F. This parameter is generally not measured and a mean conventional value ranging between 0.4 and 0.6 is assumed, possibly leading to a significant bias in the dose assessments. In this paper, a method for the measurement of F is reported, based on the total aerosol sampling on filters and immediate gross beta counting of 214Pb and 214Bi activities. Measurements are interpreted according to a Raabe-Wrenn and Jacobi simplified room model, leading to an estimate of the individual airborne activities of short-lived radon daughters, the removal parameter and the equilibrium factor. The method was laboratory tested and validated and it is being qualified by field surveys in different indoor environmental conditions.

Outdoor radon concentration measurements: some correlation with major urban pollutants.

Air pollutants concentration in the urban air strongly depends on the properties of the planetary boundary layer (the lower region of the atmosphere), roughly up to 1 km from Earth's surface. Radioactive radon gas has been recognised by various authors as a valuable natural tracer of transport and dispersion within this layer. To achieve a better comprehension of the urban pollution dynamic in the town of Alessandria, situated in the Po Valley in the north-west of Italy, a system for continuous measurement of radon concentration in outdoor air was experimented. This paper presents the first results obtained: the hourly trend of radon concentration in the diurnal course during different seasons and its correlation with the concentration of the major urban pollutants.

Development of an electrolysis system for tritium enrichment in superficial water samples.

Tritium present in the environment gradually decreased in the last decades and nowadays it has reached extremely low activity concentrations. The purpose of the present work is the implementation of a tritium enrichment system in water samples using electrolytic techniques and pure nickel and iron electrodes. In the present work a mean tritium enrichment factor of 13.0 +/- 3.2 was obtained. This result should allow to reach a minimum detectable activity of tritium in water samples of about 1 tritium unit (TU) or less. The present enrichment system necessitates further adjustments and improvements, such as a cooling system in order to reduce the tritium losses due to evaporation.

Gamma dose rate calculation and mapping of piemonte (North-West Italy) from gamma spectrometry soil data.

In this study the air gamma dose rate map of Piemonte, a region in the North-West of Italy, was produced from gamma spectrometry soil data. Soil samples collected in 110 different sites of Piemonte were analysed with Hyperpure Germanium (HPGe) detectors (30% relative efficiency), which allow the evaluation of the activity concentrations of natural radionuclides and (137)Cs. Then, using the available mathematical models, the gamma absorbed dose rate in air due to radionuclides was calculated. The contribution of the cosmic radiation to the total absorbed dose rate, which depend on the site altitude was also evaluated and added to the soil contribution. Finally, the map of the whole region was obtained by fitting the dose rate values of the different sites with kriging algorithms.

[Chronic inflammation and airway remodeling in asthma. Importance of an early treatment]. / Flogosi cronica e rimodellamento delle vie aeree nell'asma. Importanza dell'intervento precoce.

Chronic inflammation in asthma stimulates complex repair mechanisms which ultimately lead to deep structural changes in the bronchial tree, defined as airway remodeling, consisting principally in the thickening of the bronchial wall. These processes contribute to progressive airway narrowing with incomplete responsiveness to bronchodilating agents: clinical conditions of patients are irreversibly impaired. There is evidence that remodeling is a process that begins in early childhood and continues into adult life. These observations provide the rationale for early intervention with antiinflammatory drugs like inhaled corticosteroids, which effectively reduce airway inflammation and possibly prevent the progression to lung damage. Several clinical and pharmacological studies have demonstrated that these drugs inhibit cellular processes involved remodeling.

[Management of pediatric asthma]. / La gestione dell'asma pediatrico.

Bronchial asthma, in adults and children, is a major health problem, with prevalence rates ranging from 4% to 7% in western Europe. Observational studies suggest that in Italy, like in the other countries, asthma is poorly controlled: most patients report frequent symptoms and limitation to daily activities; the utilization of healthcare resources (hospitalization, emergency room visits, unscheduled urgent care visit) is high. Recent international guidelines (GINA) for asthma management, together with an up-date by NIH, point to the primary role of inhaled corticosteroids for the control of the disease. Early interention with anti-inflammatory drugs is important, also in pre-school children with frequent or persistent symptoms, in order to prevent irreversible structural alterations of the airways and to improve long-term prognosis. In the presence of more severe asthma, inhaled corticosteroids can be associated with long-acting beta2-agonists bronchodilators. These 2 drug classes target different and complementary aspects of the pathophysiology of asthma (inflammation and bronchial obstruction) in a synergistic manner, i.e. by mutual potentiation of their pharmacological activity. Thus, combination therapy may optimize beneficial actions, allowing a more effective control of asthma.

[Fluticasone propionate in the treatment of airway inflammations (asthma and rhinitis)]. / Fluticasone propionato nella terapia delle infiammazioni delle vie aeree (asma e rinite).

Inflammation is the pathogenetic basis of many airway diseases like asthma and rhinitis. This provides the rationale for a therapy with antiinflammatory drugs like inhaled corticosteroids (ICS), which are able to suppress the underlying pathologic processes, ensuring an effective control of the disease and improving patients's quality of life. Within ICS, fluticasone is endowed of a potent antiinflammatory activity, due to its high affinity for the the glucocorticoid receptor (allowing the use of 50% of the dose of other ICS) and of a negligible oral bioavailability (<1%), indicating a low potential for systemic exposure. Due to its high therapeutical index, fluticasone can be used in the management of severe asthma or other airway diseases at doses devoid of relevant unwanted systemic effects. Scientific literature has broadly demonstrated its efficacy and safety, even at high doses and in the long term use.

The influence of clay mineralogy on the mobility of radiocaesium in upland soils of NW Italy.

137Cs extraction experiments were performed on 14 contaminated soils from NW Italy with different characteristics and mineralogical composition. Solutions of HCl (pH = 0.5) and buffered EDTA/ammonium acetate (Lakanen solution) were used to assess bioavailability. The results show that less than 2% of 137Cs is available for leaching and/or root uptake. Even within a complex natural system it was possible to identify the amount of swelling clays (vermiculite + smectite) as the main control on Cs mobility under acidic conditions. The ammonium ion appears to be effective in desorbing Cs and its role is briefly discussed in terms of crystal chemistry. The relevance of mineralogy in assessing soil vulnerability is underlined.

Comparison of different methods for the assessment of the environmental gamma dose.

Four different techniques for the assessment of environmental gamma dose are discussed and compared: high pressure ionisation chamber (Reuter-Stokes type), TLD dosemeters (GR-200), in situ gamma ray spectrometry and dose evaluation from the activity concentration of radionuclides in the soil. Soil samples gathered from a field near Turin (North-West Italy) have been analysed with a p-type HPGe, and their radionuclide concentrations have been used to evaluate the dose at I m above the soil surface. At the same location the dose rate was evaluated with the in situ gamma ray spectrometry (with a portable n-type HPGe) and with the ionisation chamber and the TLD dosemeters. The contribution of cosmic rays was added to the dose rate calculated from the soil samples and the in situ gamma spectrometry. The results obtained with these four techniques agree well within 20%.

Variations of the isotopic ratios of uranium in environmental samples containing traces of depleted uranium: theoretical and experimental aspects.

The possibility of using conventional analysis, such as gamma spectrometry and alpha spectrometry, for the detection of traces of depleted uranium (DU) in environmental samples has been investigated. The expected values have been compared with the experimental results obtained by using mollusc samples gathered in the Adriatic Sea. The analysis has shown that it is possible to detect DU. if the percentage composition is about 20% depleted uranium and 80% natural uranium, for a sample containing 10 Bq x kg(-1) of 238U. The possibility of extending this approach to samples with any given uranium concentration is investigated.

The aging brain: protein phosphorylation as a target of changes in neuronal function.

There is evidence that senescence affects neurotransmission at different levels. In particular, this review summarizes the studies on age-dependent modifications in protein phosphorylation, which represents the final pathway in the action of transmitters and hormones at neuronal level. Cyclic AMP-dependent protein kinase and protein kinase C have been reported to be modified during aging in various cerebral areas; the changes may involve either enzyme activity or substrate availability. These findings can be related to the alterations in neurotransmitter function and synaptic efficiency observed in the senescent brain. The activity of the other types of protein kinases (tyrosine-, cGMP-, calcium/calmodulin-dependent) during aging needs to be explored. An emerging point is the role of protein phosphorylation in the transfer of membrane signals to the nucleus, for the activation or disactivation of specific genes responsible for long-term neuronal events. Along this view, alterations in protein kinase pathway during senescence would ultimately affect gene expression, resulting in long term modifications of cell function. The reviewed literature opens the perspective of restoring some of the deficits associated with senescence by modulating protein phosphorylation pathway.