Search results for: Emanuela Velo

Authors: Emanuela Zilli, Antonio Madia, Milvia Marchiori, Paola Anello, Chiara Cabbia, Emanuela Velo, Delia Campagnolo, Michele Scomazzon, Emanuela Salvatico, S. Tikvina, Antonio Miotti

Abstract:

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). Antiviral medicines can cure more than 95% of cases of hepatitis C infection, but access to diagnosis and treatment remains low. The ULSS 6 Euganea – Health Trust has implemented a campaign to eradicate hepatitis C in the province of Padua (North-East of Italy), which can be subdivided into three areas: North (300.000 inhabitants), Centre (400.000) and South (300.000). In September 2021, the project was launched in the Northern area; a set of brochures was distributed in outpatient services, general practitioners’ clinics and offices, community pharmacy services, social health districts, and through social networks. The Hepatology Service contacted 460 patients selected by the Clinical Laboratory (positivity for HCV antibodies): 83 patients (18.0%) had been already cured of HCV infection, missing or deceased; 377 patients (82.0%) met the criteria to be eligible for HCV eradication therapy and were therefore included in a Day Service specific agenda and followed by a multidisciplinary team of healthcare professionals, with a dedicated telephone line. Haemato-chemical tests, general medical check-ups and ultrasound tests with fibroscan were performed. Patients were tested for Sars-CoV-2 positivity; those not yet vaccinated against Covid-19 were encouraged to complete the vaccination scheme. All 377 patients (100%) received HCV eradication therapy at the community pharmacy service; a detailed explanation of how to take their medication was provided. At the end of the first phase, Covid-19 vaccination rate was 100% (377/377), including patients already vaccinated and new-vaccinated. Check-up appointments were arranged after 2 or 3 months, according to the treatment plan. The awareness campaign and the organization of HCV eradication therapy service by ULSS 6 Euganea are proving to be effective; the project is now going to be applied to Central and Southern areas of the province (1.132 patients).

Keywords: public health, HCV-eradication, Covid-19 emergency, health communication strategies

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Authors: Antonio Marco Miotti, Antonella Ruffatto, Giampaola Basso, Antonio Madia, Giulia Zavatta, Emanuela Salvatico, Emanuela Zilli

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A National Action Plan to fight antimicrobial resistance was launched in Italy in 2017. In order to reduce inappropriate exposure to antibiotics and infections from multi-drug resistant bacteria, it is essential to set up a structured system of surveillance and monitoring of the implementation of National Action Plan standards, including antimicrobial consumption, with a special focus on quinolones, third generation cephalosporins and carbapenems. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Pharmaceutical Service to the Hospital of Cittadella, ULSS 6 Euganea – Health Trust (District of Padua) for the years 2019 (before the pandemic), 2020 and 2021 for all classes of antibiotics. Multidisciplinary meetings have been organized monthly by the local Antimicrobial Stewardship Group. Between 2019 and 2021, an increase in the consumption of carbapenems in the Intensive Care Unit (from 12.2 to 18.2 DDD, + 49.2%) and a decrease in Medical wards (from 5.3 to 2.6 DDD, - 50.9%) was reported; a decrease in the consumption of quinolones in Intensive Care Unit (from 17.2 to 10.8 DDD, - 37.2%), Medical wards (from 10.5 to 6.6 DDD, - 37.1%) and Surgical wards (from 10.2 to 9.3 DDD, - 8.8%) was highlighted; an increase in the consumption of third generation cephalosporins in Medical wards (from 18.1 to 22.6 DDD, + 24,1%) was reported. Finally, after an increase in the consumption of macrolides between 2020 and 2019, in 2021, a decrease was reported in the Intensive Care Unit (DDD: 8.0 in 2019, 18.0 in 2020, 6.4 in 2021) and Medical wards (DDD: 9.0 in 2019, 13.7 in 2020, 10.9 in 2021). Constant monitoring of antimicrobial consumption and timely identifying of warning situations that may need a specific intervention are the cornerstone of Antimicrobial Stewardship programs, together with analysing data on bacterial resistance rates and infections from multi-drug resistant bacteria.

Keywords: carbapenems, quinolones, antimicrobial, stewardship

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Authors: Emanuela Paranhos Lima, Vitaly Félix Rodríguez Esquerre

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In this work, efficient directional coupler composed of dielectric waveguides and metallic film has been analyzed in details by simulations using finite element method (FEM). The structure consists of a step-index fiber with dielectric core, silica cladding, and a metal nanowire parallel to the core. The results show that an efficient conversion of optical dielectric modes to long range plasmonic is possible. Low insertion losses in conjunction with short coupling length and a broadband operation can be achieved under certain conditions. This kind of couplers has potential applications for the design of photonic integrated circuits for signal routing between dielectric/plasmonic waveguides, sensing, lithography, and optical storage systems. A high efficient focusing of light in a very small region can be obtained.

Keywords: directional coupler, finite element method, metallic nanowire, plasmonic, surface plasmon polariton, superfocusing

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Authors: Parimalah Velo, Ahmad Zakaria

Abstract:

Introduction: Monte Carlo simulations of preclinical imaging systems allow opportunity to enable new research that could range from designing hardware up to discovery of new imaging application. The simulation system which could accurately model an imaging modality provides a platform for imaging developments that might be inconvenient in physical experiment systems due to the expense, unnecessary radiation exposures and technological difficulties. The aim of present study is to validate the Monte Carlo simulation of thyroid phantom imaging using Geant4-GATE for Siemen’s e-cam single head gamma camera. Upon the validation of the gamma camera simulation model by comparing physical characteristic such as energy resolution, spatial resolution, sensitivity, and dead time, the GATE simulation of thyroid phantom imaging is carried out. Methods: A thyroid phantom is defined geometrically which comprises of 2 lobes with 80mm in diameter, 1 hot spot, and 3 cold spots. This geometry accurately resembling the actual dimensions of thyroid phantom. A planar image of 500k counts with 128x128 matrix size was acquired using simulation model and in actual experimental setup. Upon image acquisition, quantitative image analysis was performed by investigating the total number of counts in image, the contrast of the image, radioactivity distributions on image and the dimension of hot spot. Algorithm for each quantification is described in detail. The difference in estimated and actual values for both simulation and experimental setup is analyzed for radioactivity distribution and dimension of hot spot. Results: The results show that the difference between contrast level of simulation image and experimental image is within 2%. The difference in the total count between simulation and actual study is 0.4%. The results of activity estimation show that the relative difference between estimated and actual activity for experimental and simulation is 4.62% and 3.03% respectively. The deviation in estimated diameter of hot spot for both simulation and experimental study are similar which is 0.5 pixel. In conclusion, the comparisons show good agreement between the simulation and experimental data.

Keywords: gamma camera, Geant4 application of tomographic emission (GATE), Monte Carlo, thyroid imaging

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Authors: Fundime Miri, Emanuela Sulaj

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Benthic ecosystems constitute important ecological habitats, providing fundamental services for spawning, foraging, and sheltering aquatic organisms. Benthic faunal communities are characterized by a large biological diversity, supported by a great physical variety of benthic habitats. Until late, the study of meiobenthic communities in Albania has been neglectedthus excluding an important component of benthos. The present study aims to bring characteristics of distribution pattern of meiofaunal communities with further focus on nematode genus-based diversity from different intertidal habitats along Albanian Adriatic Sea Coast. The investigation area is extended from Shkodra to Vlora District, including six sandy sampling sites in beaches and areas near river estuaries. Sediment samples were collected manually in low intertidal zone by using a cylindrical corer, with an internal diameter of 5 cm. The richness onmeiofaunalmajor taxon level did not show any significant change between different sampling sites compare to significant changes in nematode diversity at genus level, with distinct nematode assemblages per sampling sites and presence of exclusive genera. All meiofaunal communities under study were dominated by nematodes. Further assessment of functional diversity on nematode assemblages exhibited changes as well on trophic groups and life strategies due to diverse feeding behaviors and c-p values of nematode genera. This study emphasize the need for lower level taxonomic identification of meiofaunal organisms and extending of ecological assessments on trophic diversity and life strategies to understanding functional consequences.

Keywords: benthos, meiofauna, nematode genus-based diversity, functional diversity, intertidal, albanian adriatic coast

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Authors: Gianpaolo Ghiani, Emanuela Guerriero, Emanuele Manni, Alessandro Romano

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In this article, we deal with a variant of the classical course timetabling problem that has a practical application in many areas of education. In particular, in this paper we are interested in high schools remedial courses. The purpose of such courses is to provide under-prepared students with the skills necessary to succeed in their studies. In particular, a student might be under prepared in an entire course, or only in a part of it. The limited availability of funds, as well as the limited amount of time and teachers at disposal, often requires schools to choose which courses and/or which teaching units to activate. Thus, schools need to model the training offer and the related timetabling, with the goal of ensuring the highest possible teaching quality, by meeting the above-mentioned financial, time and resources constraints. Moreover, there are some prerequisites between the teaching units that must be satisfied. We first present a Mixed-Integer Programming (MIP) model to solve this problem to optimality. However, the presence of many peculiar constraints contributes inevitably in increasing the complexity of the mathematical model. Thus, solving it through a general purpose solver may be performed for small instances only, while solving real-life-sized instances of such model requires specific techniques or heuristic approaches. For this purpose, we also propose a heuristic approach, in which we make use of a fast constructive procedure to obtain a feasible solution. To assess our exact and heuristic approaches we perform extensive computational results on both real-life instances (obtained from a high school in Lecce, Italy) and randomly generated instances. Our tests show that the MIP model is never solved to optimality, with an average optimality gap of 57%. On the other hand, the heuristic algorithm is much faster (in about the 50% of the considered instances it converges in approximately half of the time limit) and in many cases allows achieving an improvement on the objective function value obtained by the MIP model. Such an improvement ranges between 18% and 66%.

Keywords: heuristic, MIP model, remedial course, school, timetabling

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Authors: Emanuela Zilli, Antonella Ruffatto, Davide Bonaldo, Stefano Bevilacqua, Tommaso Caputo, Luisa Fontana, Carmelina Saraceno, Antonio Sturaroo, Teodoro Sava, Antonio Madia

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The new Hospital in Cittadella - ULSS 6 Euganea Health Trust, in the North-East of Italy (400 beds, project completion date in 2026), will partially take the place of the existing building. Interesting features have been suggested in order to project a modern, “environmental-friendly” and “people-friendly” building. Specific multidisciplinary meetings (involving stakeholders and professionals with different backgrounds) have been organized on a periodic basis in order to guarantee the appropriate implementation of logistic and organizational solutions related to eco-sustainability, integration with the context, and the concept of “design for all” and “humanization of care.” The resulting building will be composed of organic shapes determined by the external environment (sun movement, climate, landscape, pre-existing buildings, roads) and the needs of the internal environment (areas of care and diagnostic-treatment paths reorganized with experience gained during the pandemic), with extensive use of renewable energy, solar panels, a 4th-generation heating system, sanitised and maintainable surfaces. There is particular attention to the quality of the staff areas, which include areas dedicated to psycho-physical well-being (relax points, yoga gym), study rooms, and a centralized conference room. Outdoor recreational spaces and gardens for music and watercolour therapy will be included; atai-chi gym is dedicated to oncology patients. Integration in the urban and social context is emphasized through window placement toward the gardens (maternal-infant, mental health, and rehabilitation wards). Service areas such as dialysis, radiology, and labs have views of the medieval walls, the symbol of the city’s history. The new building has been designed to pursue the maximum level of eco-sustainability, harmony with the environment, and integration with the historical, urban, and social context; the concept of humanization of care has been considered in all the phases of the project management.

Keywords: environmental-friendly, humanization, eco-sustainability, new hospital

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Authors: Yuri Melis, Mattia Resteghini, Emanuela Apicella, Eugenia Dozio, Leonardo Mendolicchio

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Aim: This retrospective study was created to analyze the psychometric, anthropometric and body composition values in patients at the beginning and the discharge of their of hospitalization in the residential care clinic for eating and feeding disorders (EFD’s). Method: The sample was composed by (N=59) patients with mean age N= 33,50, divided in subgroups: Anorexia Nervosa (AN) (N=28), Bulimia Nervosa (BN) (N=13) and Binge Eating Disorders (BED) (N=14) recruited from a residential care clinic for eating and feeding disorders. The psychometrics level was measured with self-report questionnaires: Eating Disorders Inventory-3 (EDI-3) The Body Uneasiness Test (BUT), Minnesota Multiphasic Personality Inventory (MMPI – 2). The anthropometric and nutritional values was collected by Body Impedance Assessment (B.I.A), Body mass index (B.M.I.). Measurements were made at the beginning and at the end of hospitalization, with an average time of recovery of about 8,6 months. Results: The all data analysis showed a statistical significance (p-value >0,05 | power size N=0,950) in variation from T0 (start of recovery) to T1 (end of recovery) in the clinical scales of MMPI-2, AN group (Hypocondria T0 64,14 – T1 56,39) (Depression T0 72,93 – T1 59,50) (Hysteria T0 61,29 – T1 56,17) (Psychopathic deviation T0 64,00 – T1 60,82) (Paranoia T0 63,82 – T1 56,14) (Psychasthenia T0 63,82 – T1 57,86) (Schizophrenia T0 64,68 – T1 60,43) (Obsessive T0 60,36 – T1 55,68); BN group (Hypocondria T0 64,08 – T1 47,54) (Depression T0 67,46 – T1 52,46) (Hysteria T0 60,62 – T1 47,84) (Psychopathic deviation T0 65,69 – T1 58,92) (Paranoia T0 67,46 – T1 55,23) (Psychasthenia T0 60,77 – T1 53,77) (Schizophrenia T0 64,68 – T1 60,43) (Obsessive T0 62,92 – T1 54,08); B.E.D groups (Hypocondria T0 59,43 – T1 53,14) (Depression T0 66,71 – T1 54,57) (Hysteria T0 59,86 – T1 53,82) (Psychopathic deviation T0 67,39 – T1 59,03) (Paranoia T0 58,57 – T1 53,21) (Psychasthenia T0 61,43 – T1 53,00) (Schizophrenia T0 62,29 – T1 56,36) (Obsessive T0 58,57 – T1 48,64). EDI-3 report mean value is higher than clinical cut-off at T0, in T1, there is a significant reduction of the general mean of value. The same result is present in the B.U.T. test in the difference between T0 to T1. B.M.I mean value in AN group is (T0 14,83 – T1 18,41) BN group (T0 20 – T1 21,33) BED group (T0 42,32 – T1 34,97) Phase Angle results: AN group (T0 4,78 – T1 5,64) BN (T0 6 – T1 6,53) BED group (T0 6 – T1 6,72). Discussion and conclusion: The evident presence that on the whole sample, we have an altered serious psychiatric and clinic conditions at the beginning of recovery. The interesting conclusions that we can draw from this analysis are that a multidisciplinary approach that includes the entire care of the subject: from the pharmacological treatment, analytical psychotherapy, Psychomotricity, nutritional rehabilitation, and rehabilitative, educational activities. Thus, this Multidisciplinary treatment allows subjects in our sample to be able to restore psychopathological and metabolic values to below the clinical cut-off.

Keywords: feeding and eating disorders, anorexia nervosa, care clinic treatment, multidisciplinary treatment

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Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

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Authors: Tommaso Adamo, Gianpaolo Ghiani, Antonio Domenico Grieco, Emanuela Guerriero

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Batch production plants provide a wide range of scheduling problems. In pharmaceutical industries a batch process is usually described by a recipe, consisting of an ordering of tasks to produce the desired product. In this research work we focused on pharmaceutical production processes requiring the culture of a microorganism population (i.e. bacteria, yeasts or antibiotics). Several sources of uncertainty may influence the yield of the culture processes, including (i) low performance and quality of the cultured microorganism population or (ii) microbial contamination. For these reasons, robustness is a valuable property for the considered application context. In particular, a robust schedule will not collapse immediately when a cell of microorganisms has to be thrown away due to a microbial contamination. Indeed, a robust schedule should change locally in small proportions and the overall performance measure (i.e. makespan, lateness) should change a little if at all. In this research work we formulated a constraint programming optimization (COP) model for the robust planning of antibiotics production. We developed a discrete-time model with a multi-criteria objective, ordering the different criteria and performing a lexicographic optimization. A feasible solution of the proposed COP model is a schedule of a given set of tasks onto available resources. The schedule has to satisfy tasks precedence constraints, resource capacity constraints and time constraints. In particular time constraints model tasks duedates and resource availability time windows constraints. To improve the schedule robustness, we modeled the concept of (a, b) super-solutions, where (a, b) are input parameters of the COP model. An (a, b) super-solution is one in which if a variables (i.e. the completion times of a culture tasks) lose their values (i.e. cultures are contaminated), the solution can be repaired by assigning these variables values with a new values (i.e. the completion times of a backup culture tasks) and at most b other variables (i.e. delaying the completion of at most b other tasks). The efficiency and applicability of the proposed model is demonstrated by solving instances taken from Sanofi Aventis, a French pharmaceutical company. Computational results showed that the determined super-solutions are near-optimal.

Keywords: constraint programming, super-solutions, robust scheduling, batch process, pharmaceutical industries

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Authors: E. Mas de les Valls, M. Castells-Sanabra, R. Capdevila, N. Pla, Rosa M. Fernandez-Canti, V. de Medina, A. Mujal, C. Barahona, E. Velo, M. Vigo, M. A. Santos, T. Soto

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Absenteeism in universities, including polytechnical universities, is influenced by a variety of factors. Some factors overlap with those causing absenteeism in schools, while others are specific to the university and work-related environments. Indeed, these factors may stem from various sources, including students, educators, the institution itself, or even the alignment of degree curricula with professional requirements. In Spain, there has been an increase in absenteeism in polytechnical university studies, especially after the Covid crisis, posing a significant challenge for institutions to address. This study focuses on Universitat Politècnica de Catalunya• BarcelonaTech (UPC) and aims to quantify the current level of absenteeism and identify its main causes. The study is part of the teaching innovation project ASAP-UPC, which aims to minimize absenteeism through the redesign of teaching methodologies. By understanding the factors contributing to absenteeism, the study seeks to inform the subsequent phases of the ASAP-UPC project, which involve implementing methodologies to minimize absenteeism and evaluating their effectiveness. The study utilizes surveys conducted among students and polytechnical companies. Students' perspectives are gathered through both online surveys and in-person interviews. The surveys inquire about students' interest in attending classes, skill development throughout their UPC experience, and their perception of the skills required for a career in a polytechnical field. Additionally, polytechnical companies are surveyed regarding the skills they seek in prospective employees. The collected data is then analyzed to identify patterns and trends. This analysis involves organizing and categorizing the data, identifying common themes, and drawing conclusions based on the findings. This mixed-method approach has revealed that higher levels of absenteeism are observed in large student groups at both the Bachelor's and Master's degree levels. However, the main causes of absenteeism differ between these two levels. At the Bachelor's level, many students express dissatisfaction with in-person classes, perceiving them as overly theoretical and lacking a balance between theory, experimental practice, and problem-solving components. They also find a lack of relevance to professional needs. Consequently, they resort to using online available materials developed during the Covid crisis and attending private academies for exam preparation instead. On the other hand, at the Master's level, absenteeism primarily arises from schedule incompatibility between university and professional work. There is a discrepancy between the skills highly valued by companies and the skills emphasized during the studies, aligning partially with students' perceptions. These findings are of theoretical importance as they shed light on areas that can be improved to offer a more beneficial educational experience to students at UPC. The study also has potential applicability to other polytechnic universities, allowing them to adapt the surveys and apply the findings to their specific contexts. By addressing the identified causes of absenteeism, universities can enhance the educational experience and better prepare students for successful careers in polytechnical fields.

Keywords: absenteeism, polytechnical studies, professional skills, university challenges

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Authors: Emanuela Zilli, Suana Tikvina, Davide Bonaldo, Monica Varotto, Scilla Rizzardi, Barbara Ruzzante, Raffaele Napolitano, Stefano Bevilacqua, Antonella Ruffatto

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A healthy workplace increases productivity, creativity and decreases absenteeism and turnover. It also contributes to creating a more secure work environment with fewer risks of violence. In the past 3 years, the healthcare system has suffered the psychological, economic and social consequences of the COVID-19 pandemic. On the other hand, the healthcare staff reductions determine high levels of work-related stress that are often unsustainable. The Hospital of Cittadella (in the province of Padua) has 400 beds and serves a territory of 300,000 inhabitants. The hospital itself counts 1.250 healthcare employees (healthcare professionals). This year, the Medical Board of Directors has requested additional staff; however, the economic situation of Italy can not sustain additional hires. At the same time, we have initiated projects that aim to increase well-being, decrease stress and encourage activities that promote self-care. One of the projects that the hospital has organized is the psychomotor practice. It is held by therapists and trainers who operate according to the traditional method. According to the literature, the psychomotor practice is specifically intended for the staff operating in the Intensive Care Unit, Emergency Department and Pneumology Ward. The project consisted of one session of 45 minutes a week for 3 months. This method brings focus to controlled breathing, posture, muscle work and movement that help manage stress and fatigue, creating a more mindful and sustainable lifestyle. In addition, a Qigong course was held every two weeks for 5 months. It is an ancient Chinese practice designed to optimize the energy within the body, reducing stress levels and increasing general well-being. Finally, Tibetan singing crystal bowls sessions, held by a music therapist, consisted of monthly guided meditation sessions using the sounds of the crystal bowls. Sound therapy uses the vibrations created from the crystal bowls to balance the vibrations within the body to promote relaxation. In conclusion, well-being and organizational performance are closely related to each other. It is crucial for any organization to encourage and maintain better physical and mental health of the healthcare staff as it directly affects productivity and, consequently, user satisfaction of the services provided.

Keywords: health promotion, healthcare workers management, Weel being and organizational performance, Psychomotor practice

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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