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Davide Costa,1,2 Raffaele Serra1,2 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology. University “magna Graecia” of Catanzaro, Catanzaro, 88100, Italy; 2Department of Medical and Surgical Sciences. University “magna Graecia” of Catanzaro, Catanzaro, 88100, ItalyCorrespondence: Raffaele Serra, Department of Medical and Surgical Sciences. University “Magna Graecia” of Catanzaro, Catanzaro, 88100, Italy, Tel +3909613647380, Email rserra@unicz.itAbstract: The concepts of disease, illness, and sickness, included in Twaddle triad, capture fundamentally different aspects of human health including medical, personal, anthropological, and social related phenomena. All the aforementioned scientific disciplines offer a variety of valuable insights, but they are not strongly connected to each other to describe a unique vision of health phenomena, and this represents a gap in the current literature. This article provides a review of the theoretical discussions on the Twaddle Triad, considering critiques and elements of interest, analyzing its connections with the concepts and the processes of recovery. The concept of recovery has been fully linked to Twaddle triad by means of its three main processes, curing, healing, and habilitating, in order to arrive to a new framework proposal that is able, connecting variables and attributes of each framing concept, to better describe and deepen multifaceted elements around different types of health problems.Keywords: illness, sickness, disease, recovery, Twaddle triad

Nicola Ielapi,1,2,&ast; Michele Andreucci,3,&ast; Umberto Marcello Bracale,4 Davide Costa,1,5 Egidio Bevacqua,6 Nicola Giannotta,1,6 Maria Grazia Bevacqua,7 Giuseppe Filiberto Serraino,7 Pasquale Mastroroberto,7 Michele Provenzano,6 Raffaele Serra1,6 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology” at the Department of Surgical and Medical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Department of Public Health and Infectious Disease, Sapienza University of Rome, Rome, Italy; 3Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 4Department of Public Health, Vascular Surgery Unit, University Federico II of Naples, Naples, Italy; 5Department of Law, Economics and Sociology, University Magna Graecia of Catanzaro, Catanzaro, Italy; 6Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Italy; 7Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy&ast;These authors contributed equally to this workCorrespondence: Raffaele SerraDepartment of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy, Email rserra@unicz.itBackground: Venous return in the circulatory system of lower limbs results from the interaction of several mechanisms and reflects the balance between blood inflow and outflow. Blood outflow improves during the lying position especially with leg elevation both in patients with chronic venous disease (CVD) and in healthy subjects in sedentary settings with short-term immobilization. This study evaluated the level of comfort of hospital inpatients, without CVD, lying with a moderate leg elevation during hospital stay.Methods: This was a clinical trial examining 60 consecutive patients referred to vascular surgery, cardiac surgery, and nephrology units. After inclusion, patients were randomly assigned to two groups: A (leg elevation) in which patients were made to lie in the hospital bed with moderate elevation of the legs, and B (no leg elevation) in which patients were made to lie in the hospital bed without leg elevation.Results: The whole population consisted of 40 patients undergoing leg elevation (group A) and 20 without leg elevation (group B). During each day of hospitalization, measurements such as ankle and calf circumference, heart rate, blood pressure, and body temperature were collected. Subjective data such as perceived heaviness in the lower limbs, comfort perception and hours of sleep were also collected. In this study, patients of group A recorded a decrease in calf and ankle circumference (delta in ankle and calf circumference (difference between end of study visit and baseline visit) were significantly decreased in group A vs group B (p< 0.001 for both sides), and patients perceived less leg heaviness and even reported more leg comfort compared to patients of Group B (p< 0.001)). Among patients of group A, the bigger advantage in terms of comfort perception was recorded in patients with 15° leg elevation.Conclusion: Moderate leg elevation during hospital stay seems to effectively improve leg comfort in hospitalized patients.Keywords: venous system, lower limb, circulation, leg elevation, hospital stay, vein symptoms, leg discomfort

Raffaele Serra,1,2,&ast; Umberto Marcello Bracale,3,&ast; Nicola Ielapi,4 Luca Del Guercio,3 Maria Donata Di Taranto,5 Maurizio Sodo,3 Ashour Michael,6 Teresa Faga,6 Egidio Bevacqua,7 Federica Jiritano,7 Giuseppe Fliberto Serraino,7 Pasquale Mastroroberto,7 Michele Provenzano,8 Michele Andreucci6 1Interuniversity Center of Phlebolymphology (CIFL), “Magna Graecia” University, Catanzaro, Italy; 2Department of Surgical and Medical Sciences, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 88100, Italy; 3Department of Public Health, University of Naples “Federico II”, Naples, Italy; 4Department of Public Health and Infectious Disease, “Sapienza” University of Rome, Roma, 00185, Italy; 5Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy; 6Department of Health Sciences, “Magna Graecia” University, Catanzaro, Italy; 7Department of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, 88100, Italy; 8Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 88100, Italy&ast;These authors contributed equally to this workCorrespondence: Raffaele SerraDepartment of Surgical and Medical Sciences, Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 88100, ItalyTel +39 09613647380Email rserra@unicz.itAbstract: Chronic kidney disease (CKD) is a clinical condition characterized by high morbidity and mortality. Globally, CKD is also increasing in prevalence and incidence. The two principal kidney measures namely estimated glomerular filtration rate (eGFR) and albuminuria have been found to be predictors of renal and cardiovascular (CV) endpoints including peripheral artery disease (PAD). The prevalence of PAD was increased in CKD patients and, particularly, in patients with more severe CKD stages. Despite the fact that revascularization strategies are suitable in CKD patients in similar fashion to non-CKD patients, few CKD patients underwent these procedures. In fact, if it is true that revascularization improves prognosis in PAD patients irrespective of baseline eGFR, it was also demonstrated that CKD patients, who underwent revascularization, were at higher risk for amputations, mortality, re-intervention and perioperative complications. With the present review article, we have examined the association between CKD, PAD and peripheral revascularization highlighting data about epidemiology, pathophysiologic mechanisms, and results from previous observational and intervention studies. We have also examined the future perspectives and challenges of research around the association between CKD and PAD.Keywords: chronic kidney disease, CKD, peripheral artery disease, PAD, ESKD, amputations, albuminuria

Raffaele Serra,1– 3 Andrea Abramo,1– 3 Nicola Ielapi,1,4 Salvatore Procopio,5 Pietro Marino3 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical and Medical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 3Department of Social Sciences, Vitambiente, Catanzaro, Italy; 4Department of Public Health and Infectious Disease, “Sapienza” University of Rome, Rome, Italy; 5Department of Catanzaro District, Laboratory of Physics, Calabria Regional Agency for Environment Protection, Catanzaro, ItalyCorrespondence: Raffaele SerraInteruniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical and Medical Sciences, University Magna Graecia of Catanzaro, Viale Europa, Località Germaneto, Catanzaro, 88100, ItalyTel +3909613647380Email rserra@unicz.itAbstract: Peripheral artery disease (PAD) of the lower limbs represents one of the most important clinical conditions among vascular disease and can negatively impact quality of life of affected patients, representing also an important socioeconomic burden. Several risk factors predispose to PAD and its complications. Nevertheless, the role of pollution in this context has not been fully evaluated and this article explored the most updated information on epidemiology and environmental pollution in order to hypothesize the possible contribution of air pollution in the onset of PAD. Pollution is an important problem for the global community and has harmful effects on human health and cardiovascular system, and, specifically, particulate matter 10 (PM10) was found significantly associated with PAD.Keywords: peripheral artery disease, pollution, environment, PM10, risk factors

Nicola Ielapi,1,2,* Michele Andreucci,3,* Noemi Licastro,1,4 Teresa Faga,3 Raffaele Grande,5 Gianluca Buffone,6 Sabrina Mellace,7 Paolo Sapienza,5 Raffaele Serra1,4 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical and Medical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy; 2Department of Public Health and Infectious Disease, “Sapienza” University of Rome, Rome, Italy; 3Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy; 4Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy; 5Department of Surgery “P. Valdoni”, “Sapienza” University of Rome, Rome, Italy; 6Department of Vascular Surgery, Health Agency of Trento, Trento, Italy; 7Department of Patient’s Service, Civic Health Agency of Trento, Trento, Italy*These authors contributed equally to this workCorrespondence: Raffaele SerraInteruniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Surgical and Medical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro 88100, ItalyTel +3909613647380Email rserra@unicz.itAbstract: Precision health, by means of the support of precision medicine and precision nursing, is able to support clinical decision making in order to tailor optimal health-care decisions, around the individual characteristics of patients. The operational arm of precision health is represented by the use of biomarkers that can give useful information about disease susceptibility, exposure, evolution and response to treatment. Omics, imaging and clinical biomarkers are actually studied for their ability to positively impact health-care management. In this article, we try to address the role of biomarkers in the context of modern medicine and nursing with the view of improving patients care.Keywords: precision medicine, precision nursing, biomarkers, precision health, evidence based medicine, evidence based nursing

Gulfiia Nagimovna Aflyatumova,1 Razina Ramazanovna Nigmatullina,2 Dinara Ilgizarovna Sadykova,3 Mariia Dmitrievna Chibireva,4 Francesco Fugetto,5 Raffaele Serra6,7 1Department of Pediatrics, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Kazan, Republic of Tatarstan, Russian Federation; 2Department of Normal Physiology, Kazan State Medical University, Kazan, Republic of Tatarstan, Russian Federation; 3Department of Hospital Pediatrics, Kazan State Medical Academy, Kazan, Republic of Tatarstan, Russian Federation; 4Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russian Federation; 5Department of Vascular Surgery, Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Headquarters: University Magna Graecia of Catanzaro, Catanzaro, Italy; 6Department of Vascular Surgery, Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Headquarters: University Magna Graecia of Catanzaro, Catanzaro, Italy; 7Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy Background: Essential arterial hypertension (EAH) in adolescents represents a social burden. The endothelium is involved in the pathogenesis of EAH. Imbalance of key vasoactive factors – namely nitric oxide (NO) and endothelin-1 (ET-1) – is observed, and serotonin (5-HT) release is also impaired. The relationship between the factors and high blood pressure (BP) has been established mainly in preclinical studies and in the adult age. The aim of the present manuscript is to establish the association between plasma ET-1, serum NO and 5-HT, platelet 5-HT levels and BP in male adolescents, analyzing their concentrations in controls, prehypertensive and hypertensive children. Consequently, we want to evaluate ET-1, NO and 5-HT levels as preclinical biomarkers of EAH. Methods: Outpatient adolescents, examined at Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, were recruited between 26th of May and 25th of September 2016. Predictor variables identified were plasma ET-1, serum NO and 5-HT levels and were evaluated in serum and platelets of case and control groups. Results: Plasma ET-1 and serum 5-HT concentrations in prehypertensive and hypertensive children were higher than in controls, with hypertensive adolescents showing higher levels of both factors compared with prehypertensive adolescents. Platelet 5-HT levels were lower in prehypertensive and hypertensive children compared with controls, while serum NO levels were higher in prehypertensive children than in hypertensive children. Conclusion: Measurable ET-1, NO and 5-HT are related to BP in adolescents and may serve as diagnostic biomarkers of EAH. Furthermore, they could help to better define prehypertensive and hypertensive children. Keywords: endothelin-1, serotonin, nitric oxide, pediatric arterial hypertension, biomarkers, pre-hypertension, monoamines, endothelial dysfunction

Michele Andreucci,1 Teresa Faga,1 Raffaele Serra,2 Giovambattista De Sarro,3 Ashour Michael1 1Renal Unit, Department of Health Sciences, 2Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Medical and Surgical Sciences, 3Pharmacology Unit, Department of Health Sciences, Magna Graecia University, Catanzaro, Italy Abstract: An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function) occurring 48–72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate

Luca Gallelli,1,* Daniela Falcone,1,* Roberto Cannataro,2 Mariarita Perri,2 Raffaele Serra,3 Girolamo Pelaia,3 Rosario Maselli,3 Rocco Savino,1 Giuseppe Spaziano,4 Bruno D’Agostino4 1Department of Health Science, University of Catanzaro, Catanzaro, 2Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, 3Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, 4Department of Experimental Medicine, School of Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy *These authors contributed equally to this work Abstract: Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli. Theophylline administrated alone was not able to reduce growth-stimulating signaling via extracellular signal-regulated kinases activation and matrix metalloproteases release, whereas it strongly counteracts this biochemical behavior when administered in the presence of corticosteroids. These data provide scientific evidence for supporting the rationale for the pharmacological use of theophylline and corticosteroid combined drug. Keywords: human bronchial epithelial cells, theophylline, corticosteroids, signal transduction

Bruno Amato,1,2,* Rita Compagna,1,2,* Aldo Rocca,2 Tommaso Bianco,2 Marco Milone,2 Luigi Sivero,2 Gabriele Vigliotti,2 Maurizio Amato,2 Michele Danzi,2 Giovanni Aprea,2 Luca Gallelli,3,* Stefano de Franciscis,1,4,* Raffaele Serra1,4,* 1Interuniversity Center of Phlebolymphology, International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 2Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, 3Department of Health Sciences, 4Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy *These authors contributed equally to this work Introduction: In cancer patients, the chest computer tomography (CT) can be used to identify asymptomatic pulmonary embolism (APE). In most cases, these patients are treated with anticoagulant drugs for at least 3 months. The American College of Physicians recommend treatment of these patients as patients with symptomatic pulmonary embolism. In this study, we evaluated and compared the efficacy and safety of fondaparinux vs warfarin in the prevention of unsuspected pulmonary embolism in patients with active cancer. Materials and methods: A prospective and parallel group study was performed on 64 cancer patients (29 males and 35 females) with APE. A multidetector CT angiography with high spatial and temporal resolution and quality of arterial opacification was used to make the diagnosis. Lung scintigraphy was reserved to selected patients only. Patients were randomized to either the warfarin (Group A) or the fondaparinux (Group B) for 90 days. The first end point of efficacy was the persistence, reduction, or disappearance of thrombosis after 90 days. The second end point was the reappearance of thrombosis after 1 year. The first end point of safety was the development of major bleeding. Results: We enrolled 32 patients into each treatment group. We reached the first end point of efficacy and safety in Group B which showed that fondaparinux was able to induce the disappearance of thrombotic pulmonary with a lower incidence of major bleeding events compared with warfarin. No difference in the secondary end point was recorded. Conclusion: We suggest that the treatment of cancer patients with APE can be oriented with the administration of a standard dose of fondaparinux until the next CT lung control (3 months). However, the lack of a randomized clinical trial, including a larger patient cohort, does not allow formulation of final recommendations in these patients. A broader study would be desirable, involving a larger number of patients and a longer follow-up period. Keywords: cancer patients, asymptomatic pulmonary embolism, fondaparinux, warfarin

Bruno Amato,1,2,* Rita Compagna,1,2,* Maurizio Amato,2 Luca Gallelli,3 Stefano de Franciscis,1,4,* Raffaele Serra1–4,*1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, 2Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, 3Department of Health Sciences, University of Catanzaro, Catanzaro, 4Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy*These authors contributed equally to this workBackground: In patients with carotid stenosis, the risk of plaque rupture is related to the composition of the atherosclerotic plaque rather than to its magnitude. In this regard, we evaluated the effects of a supplement, Aterofisiol,® containing omega-3 (EPA [eicosapen acid] DHA [docosahexaenoic acid]), vitamin K2, vitamin B6, vitamin B12, oligomeric proanthocyanidins (OPC) and resveratrol on the composition of atherosclerotic plaque and on neurological symptoms in patients with carotid stenosis undergoing carotid endarterectomy.Methods: The study was randomized, prospective, and double-blinded. Eligible patients were of both sexes, with carotid stenosis >70% who underwent endarterectomy. Enrolled patients were randomly allocated to receive either one tablet of acetylsalicylic acid 100 mg (Cardioaspirin®) + one tablet of Aterofisiol every 24 hours or one tablet of Cardioaspirin + one tablet of placebo every 24 hours. Each treatment was started 30 days before the surgery and was stopped 5 days before the surgery. The plaques were removed “en bloc” using standard surgical technique.Results: During the study period, 214 patients (135 men and 79 women) were enrolled for intent-to-treat and randomized in two groups: Group A: 107 patients (68 men and 39 women) were treated with Cardioaspirin + Aterofisiol. Group B: 107 patients (67 men and 40 women) were treated with Cardioaspirin + placebo. At the end of the study, 202 patients participated fully (103 patients in Group A and 99 patients in Group B), making up the protocol evaluation population (94.4%). The mean lipid content of removed plaques was significantly lower (P

Carmelinda Ruggiero,1 Elena Zampi,1 Giuseppe Rinonapoli,2 Marta Baroni,1 Rocco Serra,1 Elisa Zengarini,1 Gregorio Baglioni,3 Giuliana Duranti,3 Sara Ercolani,1 Francesco Conti,4 Auro Caraffa,2 Patrizia Mecocci,1 Maria Luisa Brandi5 1Geriatric Unit, University of Perugia, Hospital S Maria della Misericordia, 2Orthopedic and Traumatologic Unit, University of Perugia, Hospital S Maria della Misericordia, 3Primary Care Physicians, SIMG Umbria, Perugia, 4Department of Clinical and Molecular Medicine, Sapienza University of Rome, AO Sant’Andrea Hospital, Rome, 5Department of Internal Medicine, University of Florence, Florence, Italy Background: A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment.Methods: This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post-intervention phase. The records of 172 participants were evaluated in the pre-intervention phase, while data from 210 participants were gathered in the post-intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures.Results: Compared with the pre-intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P

Raffaele Serra,1,2,* Luca Gallelli,3,* Angela Conti,1 Giovanni De Caridi,4 Mafalda Massara,4 Francesco Spinelli,4 Gianluca Buffone,1 Francesco Giuseppe Caliò,5 Bruno Amato,6 Simona Ceglia,7 Giuseppe Spaziano,8 Luca Scaramuzzino,9 Alessia Giovanna Ferrarese,10 Raffaele Grande,1 Stefano de Franciscis1,2 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 3Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 4Cardiovascular and Thoracic Department, University of Messina, Messina, Italy; 5Unit of Vascular Surgery, S Anna Hospital, Catanzaro, Italy; 6Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 7Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy; 8Department of Experimental Medicine, Second University of Naples, Naples, Italy; 9University Campus BioMedico of Rome, Rome, Italy; 10Department of General Surgery, University of Turin, Turin, Italy *These authors contributed equally to this work Background: Mixed venous and arterial ulcers account for approximately 15%–30% of all venous leg ulcerations. Several studies have shown that matrix metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL) play a central role in the pathophysiology of venous and arterial diseases. Some studies have shown the efficacy of glycosaminoglycans, such as sulodexide (SDX), in treating patients with leg ulcers. The aim of this study was to evaluate clinical effects of SDX and its correlation with MMPs and NGAL expression in patients with mixed arterial and venous leg ulcers. Methods: Patients eligible for this study were of both sexes, older than 20 years, and with a clinical and instrumental diagnosis of mixed ulcer. Results: Fifty-three patients of both sexes were enrolled and divided into two groups by means of randomization tables. Group A (treated group) comprised 18 females and ten males (median age: 68.7 years) treated with standard treatment (compression therapy and surgery) + SDX (600 lipoprotein lipase-releasing units/day intramuscularly) for 15 days followed by SDX 250 lipase-releasing units every 12 hours day orally for 6 months as adjunctive treatment. Group B (control group) comprised 17 females and eight males (median age: 64.2 years) treated with standard treatment only (compression therapy and surgery). The type of surgery was chosen according to anatomical level of vein incompetence: superficial venous open surgery and/or subfascial endoscopic perforating surgery. In all enrolled patients, blood samples were collected in order to evaluate the plasma levels of MMPs and NGAL through enzyme-linked immunosorbent assay. These results were compared to another control group (Group C) of healthy individuals. Moreover, biopsies of ulcers were taken to evaluate the tissue expression of MMPs and NGAL through Western blot analysis. Our results revealed that SDX treatment is able to reduce both plasma levels and tissue expression of MMPs improving the clinical conditions in patients with mixed ulcers. Conclusion: Inhibition of MMPs could represent a possible therapeutic intervention to limit the progression of leg ulceration. In particular, our findings demonstrate the efficacy of SDX in patients with mixed arterial and venous chronic ulcers of the lower limbs. Keywords: mixed ulcer, arterial ulcer, metalloproteinases, neutrophil gelatinase-associated lipocalin

This study presents a frequency-band subspace-based damage identification method for faults diagnosis in roller bearing. The main purpose is to obtain damage sensitive indicators in the frequency range where a damage is expected to appear. The proposed method is validated using the data collected from bearing run-to-failure tests. It is shown that the proposed method can detect bearing defects at an early stage of development and appears therefore as an efficient tool for diagnosis purposes.

In this contribution, a bi-objective robust optimization of cutting parameters, with the taking into account uncertainties inherent in the tool wear and the tool deflection for a turning operation is presented. In a first step, we proceed to the construction of substitution models that connect the cutting parameters to the variables of interest based on design of experiments. Our two objectives are the best machined surface quality and the maximum productivity under consideration of limitations related to the vibrations and the range of the three cutting parameters. Then, using the developed genetic algorithm that based on a robust evaluation mechanism of chromosomes by Monte-Carlo simulations, the influence and interest of the uncertainties integration in the machining optimization is demonstrated. After comparing the classical and robust Pareto fronts, A surface quality less efficient but robust can be obtained with the consideration of uncontrollable factors or uncertainties unlike that provides the deterministic and classical optimization for the same values of productivity.

The objective of the paper is to evaluate the effects of cutting parameters in terms of cutting speed, depth of cut and feed rate on the influence of the surface roughness, consumed power, cutting time and tool vibrations during turning process. The material chosen in this case was 100C6 steel in dry conditions. The effects of the selected process parameters have been investigated using full factorial design of experiments (33) and the multiple linear regression (MLR). Thus, first-order empirical models were established. Analysis of variance (ANOVA) was employed to check the validity of the developed models within the limits of the factors that were being investigated and to test the significance of the above parameters. Results indicate that the feed rate is the only significant factor affecting the surface roughness. The cutting speed and feed rate are the most influential factors on cutting time. Estimated tool vibrations are functions of cutting speed, feed rate and depth of cut in decreasing order. Finally, the models obtained can be used for determination of optimal settings of cuttings parameters and this methodology should help us to obtain the best process parameters for dry turning of 100C6 steel.