(XXXVII) CARRANO RAFFAELE: a) In this first year of the PhD programme, the student contributed to the publication "Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo", dealing specifically with the culture of different malignant mesothelioma cell lines. The cells were treated with two different substances: Afatinib (Afa) and Gant-61 (Gant), alone or in combination, at different concentration and with different exposure times. Subsequently, the toxicity of these treatments was assessed by a sulforhodamine B assay (SRB). The modulation of proteins expression was observed by Western Blot technique. b) He also contributed to the analysis of the in vitro effect of the bisphenol A (BPA), an endocrine disruptor used at different concentrations, on breast cancer cells. Cell survival with SRB assay and proteins expression by Western Blot technique were performed.
(XXXVII) CIMMINO ALESSIO: Natural compounds have always been one of the most important and relevant assets in drug discovery and development. Polydatin (PD), extracted from Polygonum Cuspidatum, is a natural precursor and glycoside form of resveratrol, known for its anti-inflammatory, immune-regulating and anti-oxidative function. However, studies on the association of polydatin with cancer are limited, particularly with regards to osteosarcoma (OS), the most common primary bone tumor in children and adolescents. The purpose of the present study is to reveal the potential anticancer effects of polydatin on human OS cell lines. In particular, the research activity of the first year of PhD was aimed at evaluating: 1) the inhibitory effects of PD on proliferation and migration of Saos-2 and U-2 OS cells; 2) the antioxidation activities of PD under stressful conditions; 3) the possible effects of PD treatment on expression level of proteins involved in oncogenic functions.
(XXXVII) GABRIELLI PAOLO ROBERTO: In modern football, understanding collective tactical behavior has become an integral part of sports analysis. The assessment of tactical behavior based on the multiple space-time relationships between players, allows a qualitative analysis of the progress of the match, and can improve the ability to analyze and describe actions in game.
The evolution and use of technology based on global positioning systems (GPS, GNSS, GALILEO) has over time become a fundamental element in the analysis of performance and in the evaluation of collective tactical behavior, providing ever more extensive, specific, detailed and precise information.
As the size of the volume of available data increases, the complexity of the problem also increases and the need for adequate tools indispensable to use the cognitive aspects involved in the study. Therefore, the main objective of the scientific project is to validate new metrics related to the instant positioning of the players during the game that allow a better knowledge in real time of the technical-tactical behavior of the teams.
(XXXVII) PAOLO LIDO: Hodgkin and non-Hodgkin lymphoma represent about 60% of all haematological cancers. During chemotherapy there is an acceleration of aging processes up to 24 times, therefore, prompt counteractive measures, are very much needed in this subset to mitigate/prevent cardiac, musculo-skeletal and other impairments. Supervised exercise-training (ET), during lymphoma treatment has been shown promising to this aim and safe. The main scope of this project is to assess if a hybrid counselling intervention based on both face-to-face and remote support (i.e. Supervised + Remote/individualized) protocol of ET intervention, is effective in increasing Physical Activity volumes up to 12 months. Maintenance or improvement of QoL, cardio-respiratory fitness and overall body functioning are the desired “output” of ET interventions. Therefore, the assessment of these secondary endpoints is an important task of this project.
(XXXVII) MASSARO LUCA: In last decades, due to leaps in technological advancements, the daily use of devices based on radiofrequencies (RF) (100 KHz - 300 GHz), has become widespread. These are mainly employed for communication, radiotransmission and radar system, exposing people both at home and work. This constant exposition raised concern among population and scientific community on possible health effects of RF. The current security standard adopted by the European Union, only considers the well-known thermal effects of RF. This project aims to evaluate the non-thermical biological effects correlated to RF exposure. In the first year of the project, for the "in vitro" study, the student set up the different methods planned, and performed the 2h exposure experiments at continuous 1,6 GHz on human fibroblasts. Cell cycle analysis, ultrastructural analysis, proteins expression, γ-H2AX/53PB1 assay and mRNA sequencing were performed.
(XXXVII) ILARIA PETRIGNANI: The question of how gravity has influenced the evolution of the human species is a topic of intense research in recent years, especially in relation to the growing interest in space/planetary colonization. Understand how the human organism adapts to the influence of different environmental conditions (not only in space) is a crucial first step in defining strategies for survival in environments profoundly different from those on Earth. The stimuli to which astronauts are subjected during flights or their stay in the space station are manifold, as are the responses of the 'organism to these new stimuli. Among them, microgravity induces remarkable changes in the human body such as muscle atrophy, loss of bone tissue, and immune dysfunction, just to name a few. In this context, we focused on the search for microRNAs, noncoding RNA molecules that regulate gene expression, which are responsible for modulating various processes in both skeletal and cardiac muscle tissue and bone tissue. Understanding the dynamics of microRNA expression, identifying their target genes, is necessary to determine their potential for the prevention and diagnosis of diseases such as, for example, muscle atrophy or osteoporosis.
(XXXVII) SOLLINI MARIA LAURA: Lower urinary tract symptoms (LUTS) and dysfunction are extremely common in Multiple Sclerosis (MS) and they can be very bothersome and distressing, both for the organic complications on the upper urinary tract and for the socio-economic implications and the impact on the patients’ quality of life. Urgency and frequency are the most represented symptoms, particularly in women, but also voiding dysfunction is well represented and not properly investigated. To make a correct diagnosis is important for the appropriate treatment; equally important is to know if there is a correlation with inflammatory cytokines and other clinical manifestation of MS for improving pharmacologic treatments and re-educative approach.
(XXXVI) ALLOISIO GIULIA: Mechanobiology is an emerging interdisciplinary field of biochemistry that focuses on how physical stresses interfere with cellular functions. Increasing evidence suggests that the mechanical environment has important consequences not only for the well-known preservation of bone quality and quantity but also because it may foster transformation and metastasis. In this project, the student employed the use of the Mechano Cell Flex instrument (a deformable silicone system suitable for long-term cell culture), which allows the reproduction in vitro of the uniaxial deformations that osteoblastic cells undergo in vivo. Specifically, a longer stimulation was able to cause an increase in cell number and alkaline phosphatase activity of osteoblastic cells of SAOS-2 but not of U-2 OS osteosarcoma cell line, while a shorter stimulation left the first alterations unchanged, while it was able to disrupt the morphology and migration properties of SAOS-2 cells. Cell adhesion and migration were attenuated and enhanced, respectively, following the selected stimulus. The stimulus disrupted intracellular redox homeostasis by increasing ROS in mechanically stimulated cells resulting in overexpression of the SOD1 enzyme, and altered metabolic pathways (pentose phosphate pathway, the Krebs cycle, and the glycolysis). Hence, the third-year research will be directed toward the identification of the mechanostransducer molecules to identify the molecular pathways that could be targeted to render osteosarcoma cells more sensitive to chemotherapy.
(XXXVI) EFREMOV KRISTIAN: The use of reverse shoulder arthroplasty (RSA) has dramatically increased over the past several decades. On top of it, its original indication for Rotator Cuff Arthropathy, it is now being used for a vast array of problems, including proximal humerus fractures, massive rotator cuff tears, and primary degenerative joint disease to name a few. With the improvement in the understanding of biomechanics of RSA, such as the design of more lateralized glenoid, this type of replacement can often give patients similar range of motion as an anatomic shoulder replacement. This design has led to a complication that is unique to RSA, which is scapular stress fractures. The incidence of these fractures is around 4-5% and is one of the most common complications of RSA. These can be difficult to treat, and severely impact the patient’s rehabilitation process and overall quality of life. To this day, little is known on what causes these fractures, if there are any risk factors for them, and if established surgical technique should be changed in order to decrease their incidence. The main objective of this part of the study is to identify if any degree of distalization and/or lateralization of the glenoid or humerus leads to increased risk of Scapular Spine fractures. Based on our preliminary results, too much distalization compared to the initial value, puts patient and the increased risk for Scapular spine fractures.
(XXXVI) SARA GIAMMARIA: Estimating the rate of glaucomatous visual field change provides practical assessment of disease progression and has implications for management decisions. A prospective longitudinal cohort study was conducted in a hospital-based setting from January 1991 to February 2020. The study included 40 patients receiving treatment for open-angle glaucoma and 29 healthy participants. One eye of each participant was randomly selected as the study eye. Patients with glaucoma and healthy participants received testing with standard automated perimetry every 6 months. Individual rates of mean sensitivity change were computed using ordinary least-squares regression analysis, and linear mixed-effects modeling was used to estimate the mean rates of mean sensitivity change in the 2 groups and the impact of baseline mean sensitivity, baseline age, and follow-up intraocular pressure for rate estimates.
(XXXVI) FRANCESCA PESCOSOLIDO: The microbial contamination affects several fields, such as hospital environments, food packaging, including water purification systems, textile, aeronautic, aerospace and every aspect of public life. In addition, the widespread use of antibiotics to combat bacterial infections led to the development of antibiotic-resistant bacterial strains. To avoid these events, it is necessary to develop new materials with antibacterial properties to coat hospital surfaces, furniture, medical devices, and all other surfaces exposed to high risk of contamination. The antibacterial surfaces are also interesting to design micro-structured scaffolds that support cell growth and tissue regeneration while simultaneously inhibiting bacterial colonization reducing the risk of infection. Aim of this year of PhD research was to investigate the strategies to obtain an antibacterial composite to coat surfaces, developed through preparation of the mixtures obtained combining polymeric resins with different types of antibacterial additives, then deposited on inorganic surfaces to form a protective film.
(XXXVI) SILVIA SILVESTRI: Visual neglect is a frequent and disabling consequence of right brain damage. Traditional paper-and pencil tests of neglect have limited sensitivity and ecological validity. The Baking Tray Task (BTT), instead, approaches real-life situations, because it requires participants to place 16 physical objects on a board. The number of objects placed on the left and right portions of the board provides a clinical index of visual neglect. The student focused on the E-TAN technology, an enhanced platform for BTT (E-BTT). E-BTT automatically determines the object locations on the board, and also records the sequence and timing of their placement. We used E-BTT to test 9 patients with right hemisphere damage and compared their performance with that obtained by 115 healthy participants. To this end, we developed a new method of analysis of participants’ performance, based on the use of the convex hull described by the objects on the board.
(XXXVI) SALVATORE SIMONE VULLO: Chronic non-specific low back pain (cns-LBP) is the most common form of low back pain, lasting more than 3 months, in which a clear patho-anatomic cause of pain is not recognized. While various personal factors, such as musculoskeletal disorders or poor posture, can influence the onset and chronicity of low back pain, psychosocial factors such as fear of movement, catastrophic beliefs and mood disorders also seem to play a relevant role. Over the years, low back pain has become an increasingly important social-health-care problem both for the individual and for the public health system and society. Given the reactivity of metabolites to disease states, metabolomics has the potential to improve our understanding of the pathophysiology of chronic pain conditions and identify biomarkers for use in diagnosing these conditions and monitor therapeutic efficacy to optimize patient outcomes.
(XXXVI) REKAWT HAMA RASHID KAREEM: Sudden sensorineural hearing loss (SSNHL) is considered an otologic emergency since failing to obtain effective treatment in the early stages may result in irreversible hearing loss. The incidence varies and there is no obvious gender preference. The precise mechanism of action for the etiology of abrupt sensorineural hearing loss is unclear and numerous etiological ideas with a variety of components have been offered. Spontaneous recovery occurs in 32% to 65%3 of SSNHL patients, and it is essential that therapy begins as soon as feasible. Systematic steroid therapy (SST) appears to be the most effective treatment currently in use, although it brings adverse effects. The knowledge of cochlear pharmacokinetics suggests that intratympanic steroid (ITS) therapy is a promising therapeutic method. According to previous studies, is important to determine the effectiveness and safety of intratympanic steroid treatment compared to other combined treatments, and also to find out who can benefit the most from this type of treatment. Collecting data and following patients in Iraq, the student noticed that most of the causes of sudden sensory neural hearing loss was consequence of viral infections of the cochlear nerve especially after infleunza virus of the sinuses. Most of the cases underestimated the deriving damage and did not consider the hearing defect as an emergency condition. Instead, our data point out that early intervention is crucial for recovery and combination of systemic steroid and local injection is one of the most important factors for recovery.
(XXXVI) GORAN LATIF OMER: The gold standard minimally invasive approach for the surgical management of different inflammatory and infectious illnesses of the nose and nasal canals is endoscopic sinus surgery (FESS). One of the common complications after FESS surgery is the recurrence of Benign sinonasal polyps (SNP), lesions that develop from the mucosa of the nasal cavity and/or one or more paranasal sinuses. SNP has an unidentified etiology, although most theories defines the chronic inflammation as causative of polyps and their consequences might be obstruction, rhinorrhea, congestion, anosmia, and ageusia. The loss of smell was discovered to be the most sensitive symptom for the early diagnosis of nasal polyposis recurrence. To find all the clinic-pathological factors that might identify individuals at increased risk of recurrent sinonasal polyposis following surgery, a large prospective cohorts of patients is under observation in Iraq, with the aim of preventing sinonasal polyposis recurrence after FESS. The primary outcome of the current study is the severity of the disease, which was measured by clinical examination and endoscopic findings and radiological confirmation and staging. After collecting and managing cases, we notice that those patients presenting eosinophilia were the most complicated to manage and needed continuous nasal irrigation to prevent recurrence. Patients observation instructed about key areas (blind area and hidden locations) of recurrent to be kept under consideration to prevent recurrence.
(XXXV) BARBARA FLORA: Cranioplasty is a common procedure performed to repair cranial defects. Customized cranial implants with PEEK or titanium are often used with mains high costs indeed. Polymethhyl methacrylate (PMMA) is often used to perform cranioplasty. It is biocompatible, easily shapeable and low-cost. However, its free-hand modelling often results in a poor cosmetic result. With advances of 3D printing technologies, possibilities to produce patient specific cranioplasty emerged. The student reports preliminary experience in performing patient specific customized cranioplasty comparing PMMA customized cranioplasty with 3D printed silicone molds and a direct printing with the PLA bone (Healthfil). CAD of cranioplasty were retrieved from DICOM files of patient specific head CT scan. Using 3D printed patient specific silicone molds and PMMA resulted to be effective, affordable and ensuring a good cosmetic result.
(XXXV) SANDRA MICCINILLI: Technologies are now widely used in the rehabilitation field, because they return numerical and quantitative information. The quantification of biomechanical and motor performance and the monitoring of vital parameters while carrying out rehabilitation treatment or an activity of daily life (eg. sport or job practice), helps the clinician verifying the efficacy of proposed treatments and guides him along the comprehension of the pathogenesis of disabilities. On the other hand, the development of new rehabilitative technologies, such as robots, offers both clinicians and patients new treatment strategies, which, as described in literature, are resulting efficient especially for central nervous system pathologies treatment. In this scenery are placed movement analysis technologies for gait and posture detection, wearing technologies for breathing detection and vital parameters monitoring and rehabilitative robots for severe disabilities treatment.
(XXXV) ADRIANO SILVESTRI: Lower back pain is one of the most common diseases worldwide and can occur at any age. Data from recent studies suggest that whole-body electromyostimulation (WB-EMS) is a time-effective and tailored intervention for chronic lower back pain (CLBP). The aim of this controlled trial was to compare the efficacy of a WB-EMS training and the association between WB-EMS specific training with passive stretching (Well Back System, [WBS]) on CLBP. Forty patients with CLBP, were assigned to one of the two groups: WB-EMS and WB-EMS+WBS. Both groups completed 12 sessions (8 weeks) WB-EMS protocol. The main difference was that 6 sessions of stretching on a bench system were added to the second group that performed WB-EMS training specific for back pain. Primary study endpoints were based on changes on visual analogue scale (VAS), regarding the intensity of lower back pain from baseline to 8 weeks follow-up and changes on Oswestry Low Back Disability Questionnaire (ODI), regarding activities and lifestyle. Secondary study endpoints were percentage changes of maximum trunk flexion (Sit & Reach, [SR]) and changes on assumption of painkillers from baseline to 8 weeks follow-up. Both interventions significantly improved VAS, ODI and SR values (p range: 0.04; <0.001). However, the change of VAS (-46% vs -17%, p<0.001), ODI (-53% vs -17%, p<0.001), and SR (+7 vs +3 cm, p=0.001) were significantly higher in the WB-EMS+WBS group compared to the WB-EMS group. Also, the effectiveness of the intervention on VAS and SR was faster in the WB-EMS+WBS arm. Painkillers intake in both cohorts was negligible and remained stable. The working method with WB-EMS+WBS can be a joint-friendly, individualized form to improve CLBP.
(XXXV) MIKHAIL SINELNIKOV: Reconstruction of cartilage tissue is an important aspect of modern reconstructive efforts. The student performed an experimental study, which outlines the development and in vivo application of modifiable autologous cartilage tissue scaffolds using a mesh matrix. As a result of the experiment, a novel method was developed for fixation of cartilage transplants in recipient zones in a predetermined configuration, allowing for shape retention in the recipient zone during cartilage transplantation, to develop a biocompatible and immunologically tolerable scaffold for the three-dimensional modelling of autologous cartilage grafts for reconstructive purposes. As a result of the research study, the student developed and experimentally applied novel grafting technique, which allows for the preservation of cartilage component within a biocompatible and immunologically tolerable matrix. And showed on experimental animal models the efficacy, safety and histological compatibility of this procedure, allowing for complex stable cartilage reconstruction of tissues and defect closure. Cartilage reconstruction using autologous cartilage grafts is complicated by the instability of newly transplanted tissue. In order to stabilize cartilage grafts, a three-dimensionally stable matrix was applied to stabilize the autograft and allow for full biocompatibility and trans-graft ingrowth of viable tissues. The conclusions of the study are the safety and possibility of translation to clinic.
(XXXV) ARSALAN UL HAQ: Myofibers change their orientation transmurally through the thickness of the myocardium. At the sub-endocardial region, the fibres run in right-handed helix direction, pass parallel to the mid-wall, and turn in left-handed helix direction at the sub-epicardial region. The twisting and untwisting of myofibers along these unique directions generate a blood vortex and the so called “pumping action of the heart” spiralling the blood out to the rest of the body. Mimicking this unique structure in a scaffold with proper bioelectrical cues is a fundamental prerequisite to engineer highly conductive heart tissues. Therefore, in this study an electrically conductive scaffold mimicking this bio-architecture was developed using projection microstereolithography technique. Photo-sensitive solution containing polyaniline (conductive polymer) and polyethylene glycol diacrylate (photo-sensitive polymer) was crosslinked via photo-polymerisation reaction to fabricate 3D scaffolds. Polyaniline imparted semi-conducting properties (~10-6 S/m) to the highly inert polyethylene glycol matrix (~10-9 S/m). The obtained scaffolds demonstrated well defined morphology with an average pore size of 300 ± 15.2 μm. Conductive scaffolds improved the viability of mouse cardiac progenitor cells (91%) compared to non-conductive scaffolds (88%), five days post-culture.