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The new European directive “Green Houses” aims at the decarbonization of the existing building stock. In this work, three building types widespread in Italy are analysed, virtually positioned in Palermo, Naples, and Milan. Considering that almost 60% of Italian residential buildings fall within the G and F energy classes, three energy retrofit measures are proposed (thermal insulation of vertical walls and roofs; replacement of the methane gas boiler for building heating and domestic hot water with a high temperature air-to-water heat pump; installation of a photovoltaic system), in order to reach at least D energy class based on Italian energy performance certification. A simulation-based approach is used. A declining tendency is noted in the normalized prices of the interventions when moving from detached house to terraced house and from terraced house to apartment in a tower building. Shifting from an independent to a centralized air conditioning system results in the same savings. Considering equal building features, hotter and milder climate zones reach higher energy classes; this also results in more difficult energy efficiency improvement in colder climates. Potential inequalities result from the implementation of the new European directive. Economic incentives to support the energy efficiency transition should be tailored to more specific conditions.

Philip W Stone,1 Cosetta Minelli,1 Johanna Feary,1 C Michael Roberts,2 Jennifer K Quint,1,2,* John R Hurst2,3,* 1National Heart and Lung Institute, Imperial College London, London, UK; 2National Asthma and COPD Audit Programme, Royal College of Physicians of London, London, UK; 3UCL Respiratory, University College London, London, UK*These authors contributed equally to this workCorrespondence: John R Hurst, UCL Respiratory, University College London, London, UK, Email j.hurst@ucl.ac.ukIntroduction: There is currently no accepted way to risk-stratify hospitalised exacerbations of chronic obstructive pulmonary disease (COPD). We hypothesised that the revised UK National Early Warning Score (NEWS2) calculated at admission would predict inpatient mortality, need for non-invasive ventilation (NIV) and length-of-stay.Methods: We included data from 52,284 admissions for exacerbation of COPD. Data were divided into development and validation cohorts. Logistic regression was used to examine relationships between admission NEWS2 and outcome measures. Predictive ability of NEWS2 was assessed using area under receiver operating characteristic curves (AUC). We assessed the benefit of including other baseline data in the prediction models and assessed whether these variables themselves predicted admission NEWS2.Results: 53% of admissions had low risk, 24% medium risk and 23% a high risk NEWS2 in the development cohort. The proportions dying as an inpatient were 2.2%, 3.6% and 6.5% by NEWS2 risk category, respectively. The proportions needing NIV were 4.4%, 9.2% and 18.0%, respectively. NEWS2 was poorly predictive of length-of-stay (AUC: 0.59[0.57– 0.61]). In the external validation cohort, the AUC (95% CI) for NEWS2 to predict inpatient death and need for NIV were 0.72 (0.68– 0.77) and 0.70 (0.67– 0.73). Inclusion of patient demographic factors, co-morbidity and COPD severity improved model performance. However, only 1.34% of the variation in admission NEWS2 was explained by these baseline variables.Conclusion: The generic NEWS2 risk assessment tool, readily calculated from simple physiological data, predicts inpatient mortality and need for NIV (but not length-of-stay) at exacerbations of COPD. NEWS2 therefore provides a classification of hospitalised COPD exacerbation severity.Keywords: COPD, exacerbation, hospital, NEWS2, severity

Sergio Minelli,1 Pierluca Minelli,2 Maria Rosa Montinari3 1Department of Cardiology, Local Health Unit Lecce, Lecce, Italy; 2Faculty of Medicine and Surgery “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy; 3Department of Biological and Environmental Science and Technology, University of Salento, Lecce, ItalyCorrespondence: Maria Rosa MontinariDepartment of Biological and Environmental Science and Technology, University of Salento, Complex Ecotekne, Way Monteroni, Lecce 73100, ItalyTel +39 083 229 8855Email mariarosa.montinari@unisalento.itAbstract: The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis’s pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled “Atherosclerosis – an inflammatory disease”. In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-to-injury hypothesis, up to the key role of inflammation and immunity at various stages of disease. Finally, we briefly discussed current knowledge and future trajectories of atherosclerosis research and its therapeutic implications.Keywords: atherosclerosis, history of medicine, cardiovascular disease, inflammation

Frida Milella,1 Eliana Alessandra Minelli,2 Fernanda Strozzi,2 Davide Croce3,4 1IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 2University Carlo Cattaneo - LIUC, Castellanza, Italy; 3School of Public Health, Faculty of Health Science, Witwatersrand University, Johannesburg, South Africa; 4Centre for Health Economics, Social and Health Care Management, University Carlo Cattaneo - LIUC, Castellanza, ItalyCorrespondence: Frida Milella Tel +39 347 81 14 414Email frida.milella@gmail.comBackground: Change is an ongoing process in any organizations. Over years, healthcare organizations have been exposed to multiple external stimuli to change (eg, ageing population, increasing incidence of chronic diseases, ongoing Sars-Cov-2 pandemic) that pointed out the need to convert the current healthcare organizational model. Nowadays, the topic is extremely relevant, rendering organizational change an urgency. The work is structured on a double level of analysis. In the beginning, the paper collects the overall literature on the topic of organisational change in order to identify, on the basis of the citation network, the main existing theoretical approaches. Secondly, the analysis attempts to isolate the scientific production related to the healthcare context, by analysing the body of literature outside the identified citation network, divided by clusters of related studies.Methodology: This review adopted a quantitative-based method that employs jointly systematic literature review and bibliographic network analysis. Specifically, the study applied a citation network analysis (CNA) and a co-occurrence keywords analysis. The CNA allowed detecting the most relevant papers published over time, identifying the research streams in literature.Results: The study showed four main findings. Firstly, consistent with past studies, works reviewed pointed out a convergence on the micro-level perspective for change’s analysis. Secondly, an organic viewpoint whereby individual, organization and change’s outcome contribute to any organizational change’s action has been found in its early stage. Thirdly, works reported change combined with innovation’s concept, although the structure of the relationship has not been outlined. Fourth, interestingly, contributions have been limited within the healthcare context.Conclusion: Human dimension is the primary criticality to be managed to impede failure of the re-organizational path. Individuals are not passive recipients of change: individual change acceptance has been found a key input. Few papers discussed healthcare professionals’ behaviour, and those available focused on technology-led changes perspective. In this view, individual acceptance of change within the healthcare context resulted being undeveloped and offers rooms for further analyses.Keywords: change management, organizational change, literature review, Systematic Literature Network Analysis, healthcare

Sony Chandi Shrestha,1,2 Kebreab Ghebremeskel,1 Kenneth White,1 Caterina Minelli,2 Ihab Tewfik,3 Panna Thapa,4 Sundus Tewfik5 1School of Human Sciences, London Metropolitan University, London, UK; 2Surface Technology, National Physical Laboratory, London, UK; 3Life Sciences, University of Westminster, London, UK; 4Department of Pharmacy, Kathmandu University, Dhulikhel, Nepal; 5Department of Applied Nanomolecules, Bloomsnano Limited, London, UKCorrespondence: Sony Chandi Shrestha Email soneem@gmail.comBackground: Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges.Aim: To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols.Methods: Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated.Results: The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (− 23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines.Conclusion: Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular diseases.Keywords: cardiovascular diseases, cholesterol, phytostanol ester, PSE, solid lipid nanoparticles, SLNPs, hypercholesterolemia

Biology and its disciplinary Partitions – intellectual and academic Constraints A productive confrontation between biology and philosophy should be based on a serious effort to recover a comprehensive vision of the living world as the subject of a unitary science. Key steps in the emergence of biology as the science of all living beings in the first half of the XIX century are outlined. Academic constraints and personal agendas shaping emergence and fate of individual biological disciplines are examined, with examples from developmental and evolutionary biology. Disciplinary divisions within the life sciences can be seriously limiting for the philosopher of science, much less so for the scientist, although many concepts of foundational importance for different biological disciplines are nomadic concepts that take on the most diverse meanings according to the contexts in which they are used. It is suggested to try a reversal between disciplines and key concepts, turning the latter into anchors for a potentially nomadic set of disciplines.

In the last twenty years, obsidian artefacts have been found in important and often extensive karst cavities in Southern Italy: three located in Calabria (Grotta della Monaca, and Grotta del Tesauro, in Sant’Agata di Esaro, Cosenza; Grotta Pietra Sant’Angelo in San Lorenzo Bellizzi, Cosenza), one in Puglia (Grotta di Santa Barbara in Polignano a Mare, Bari) and another in Campania (Grotta di Polla, Salerno). All these sites, that have returned a total of 151 obsidian tools, were connected to human frequentation of the underground environments that occurred during the Holocene, which can be precisely located in the vast period between the Neolithic and the Eneolithic (6th–4th millennium BC). They are mainly blades and bladelets, but also burins together with scrapers and cores, generally of small dimensions. SEM-EDS and WD-XRF absolutely non-destructive analyses carried out on these items have shown that all samples have a source area in the obsidian outcrops of the island of Lipari (Messina, Italy). These data confirm that the Aeolian island of Lipari furnished the privileged obsidian extraction outcrops for most of the Neolithic and Eneolithic archaeological sites of Southern Italy.

Pierluca Minelli,1 Maria Rosa Montinari2 1Faculty of Medicine and Surgery “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy; 2Department of Biological and Environmental Science and Technology, University of Salento, Lecce, ItalyCorrespondence: Maria Rosa MontinariDepartment of Biological and Environmental Science and Technology, Complex Ecotekne, way Monteroni, University of Salento, Lecce 73100, ItalyTel +39 83 229 8855Email mariarosa.montinari@unisalento.itAbstract: Ancient Greece was the cradle of the Mediterranean food tradition, characterized by the Mediterranean “eternal trinity” wheat - olive oil - wine, the very essence of the country’s traditional agricultural and dietary regime, enriched by a culture of sharing and commensality. This food model, subsequently adopted and spread by the Romans, was rediscovered at the end of the Second World War by two American researchers, Leland Allbaugh and Ancel Keys. With the famous Seven Countries Study, Keys demonstrated for the first time that populations practicing a Mediterranean diet - such as the Greeks and southern Italians - showed low mortality rates from ischemic heart disease compared to the peoples of Northern Europe and North America. Since then, numerous subsequent epidemiological studies and randomized clinical trials have confirmed the beneficial effects of the Mediterranean diet both in primary and secondary prevention of cardiovascular diseases. This review will focus on the origins of the Mediterranean diet from its roots and its relationship to cardiovascular disease, with a brief overview of the nutritional mechanisms that influence atherosclerosis.Keywords: mediterranean diet, cardiovascular disease, medical history

Maria Rosa Montinari,1 Sergio Minelli2 1Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy; 2Department of Cardiology, Local Health Unit Lecce, Lecce, Italy Abstract: Cardiac auscultation – even with its limitations – is still a valid and economical technique for the diagnosis of cardiovascular diseases, and despite the growing demand for sophisticated imaging techniques, clinical use of the stethoscope in medical practice has not yet been abandoned. In 1816, René-Théophile-Hyacinthe Laënnec invented the stethoscope, while examining a young woman with suspected heart disease, giving rise to mediated auscultation. He described in detail several heart and lung sounds, correlating them with postmortem pathology. Even today, a correct interpretation of heart sounds, integrated with the clinical history and physical examination, allows to detect properly most of the structural heart abnormalities or to evaluate them in a differential diagnosis. However, the lack of organic teaching of auscultation and its inadequate practice have a negative impact on the clinical competence of physicians in training, also reflecting a diminished academic interest in physical semiotic. Medical simulation could be an effective instructional tool in teaching and deepening auscultation. Handheld ultrasound devices could be used for screening or for integrating and improving auscultatory abilities of physicians; the electronic stethoscope, with its new digital capabilities, will help to achieve a correct diagnosis. The availability of innovative representations of the sounds with phono- and spectrograms provides an important aid in diagnosis, in teaching practice and pedagogy. Technological innovations, despite their undoubted value, must complement and not supplant a complete physical examination; clinical auscultation remains an important and cost-effective screening method for the physicians in cardiorespiratory diagnosis. Cardiac auscultation has a future, and the stethoscope has not yet become a medical heirloom. Keywords: auscultation, stethoscope, medical history, medical sciences, cardiac physical examination

Morgane Roulot,1,† Alessandra Minelli,2 Marco Bortolomasi,3 Elisabetta Maffioletti,2,4 Massimo Gennarelli,2,4 Marc Borsotto,1 Catherine Heurteaux,1 Jean Mazella1 1Molecular and Cellular Institute of Pharmacology, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d’Azur, Valbonne, France; 2Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy; 3Psychiatric Hospital “Villa Santa Chiara”, Verona, Italy; 4Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy †Morgane Roulot passed away on January 10, 2018 Purpose: Sortilin-derived propeptide (PE) and its synthetic analog spadin show strong antidepressant activity in rodents and, therefore, could be used as a biomarker to evaluate the clinical efficacy of antidepressant treatments. The aim of this study was to determine whether electroconvulsive therapy (ECT) modulates serum PE concentration in patients with treatment-resistant depression (TRD).Patients and methods: Forty-five patients with major depressive disorder, who met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were selected for this study.Results: We did not observe any difference in the PE levels between TRD patients and controls (z=0.10, P=0.92), but we found a strong significant increase between the PE levels measured just before (T0) and about 1 month (T2) after ECT (z=-2.82, P=0.005). A significant difference between T0 and T2 was observed only in responders (z=-2.59, P=0.01), whereas no effect was found in nonresponders (z=-1.27, P=0.20). Interestingly, we found a significant correlation between the increase in PE levels and decrease in Montgomery -Åsberg Depression Rating Scale scores for the total patient sample (P=0.03).Conclusion: This study indicates for the first time that ECT affects serum PE concentration in responders and, therefore, could contribute to the evaluation of the therapy success. Keywords: sortilin propeptide, electroconvulsive therapy, treatment-resistant depressed patients, diagnosis

Carbon dioxide and methane transport in a commercial polyimide, Matrimid 5218®, has been characterized in order to evaluate the effect of membrane thermal treatment and physical aging on its potentialities for CO2/CH4 separation. In particular, CO2 and CH4 permeabilities and diffusion coefficients were measured at three different temperatures (35, 45 and 55°C) in films pretreated at 50, 100, 150 and 200°C, respectively. The performances of each sample were examined for a period of more than 3 000 hours. Permeability and diffusivity values for both penetrants showed a marked decrease with increasing the pretreatment temperature up to 150°C and remained, then, substantially unchanged for specimens pretreated at the highest temperature. Interestingly, the samples characterized by the higher flux after film formation also showed a faster aging phenomenon, leading to a 25 % decrease of CO2 permeability in the period inspected. Conversely, the samples pretreated at temperatures of 150°C, or higher, displayed very stable transport properties for the entire duration of the monitoring campaign. At the end of the aging period considered, the differences among samples were definitely reduced, suggesting that the initial behaviors are related to different polymer structures induced by pretreatment, which slowly evolve in time towards more similar and more stable configurations. Such aging rearrangements affect both CO2 and CH4 permeability in a similar way, so that no significant changes were observed for selectivity, which showed only a slight increment by increasing the temperature of the thermal treatment or the duration of the aging period.

This study focuses on the ethical foundations of learning in virtual environments and identifies the ethical values perceived by university students and faculty in the learning process. We analyzed 235 participants, including students from different Spanish-speaking countries and virtual education teachers, and employed a design-based research methodology using quantitative tools for empirical data collection. The analysis showed that: (a) the learning experience in virtual environments is ethical; (b) responsibility, commitment, respect, solidarity, and tolerance can be considered typical of learning in virtual learning environments; and (c) students and teachers have shared ethical experiences regarding the values considered most relevant in virtual education.

O diabetes mellitus é doença metabólica que predispõe a diversas afecções, notadamente às doenças cutâneas. São de natureza variada, porém de etiologia infecciosa em sua maioria. Uma revisão detalhada sobre tais doenças, evidenciando suas características clínicas bem como uma adequada abordagem terapêutica é o tema do presente artigo.

Twenty-eight freshwater crayfish were collected from 8 streams and one small lake in the province of South Tyrol (North Italy) from autumn 1999 to spring 2001, in order to investigate the presence of branchiobdellidans. At 6 of the streams the white clawed crayfish (Austropotamobius pallipes italicus) was collected, while the noble crayfish (Astacus astacus), the exotic species: signal crayfish (Pacifastacus leniusculus) and spiny-cheek crayfish (Orconectes limosus) were respectively caught at the other 2 streams and at the lake. Except for O. limosus, branchiobdellidans were observed on all crayfish examined. On noble crayfish, specimens of Branchiobdella italica and Branchiobdella hexodonta were found on the same host. Branchiobdella italica was largely recovered from all white clawed crayfish. The specimens of signal crayfish were found to carry only Xironogiton victoriensis.