85 results on '"Panella S"'
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2. Input Energy Spectra for Pulse-Like Ground Motions
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Frau, C., Panella, S., Tornello, M., di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Varum, Humberto, editor, Benavent-Climent, Amadeo, editor, and Mollaioli, Fabrizio, editor
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- 2023
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3. Status and challenges for the concept design development of the EU DEMO Plant Electrical System
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Gaio, E., Ferro, A., Lampasi, A., Maistrello, A., Dan, M., Falvo, M.C., Gasparini, F., Lunardon, F., Magnanimo, A., Manganelli, M., Minucci, S., Panella, S., Proietti Cosimi, M., Ratti, D., Barucca, L., Ciattaglia, S., Franke, T., Federici, G., and Piovan, R.
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- 2022
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4. Particle acoustic detection in gravitational wave aluminum resonant antennas
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Buonomo, B., Coccia, E., D'Antonio, S., Monache, G. Delle, Di Gioacchino, D., Fafone, V., Ligi, C., Marini, A., Mazzitelli, G., Modestino, G., Panella, S., Pizzella, G., Quintieri, L., Roccella, S., Ronga, F., Tripodi, P., and Valente, P.
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General Relativity and Quantum Cosmology - Abstract
The results on cosmic rays detected by the gravitational antenna NAUTILUS have motivated an experiment (RAP) based on a suspended cylindrical bar, which is made of the same aluminum alloy as NAUTILUS and is exposed to a high energy electron beam. Mechanical vibrations originate from the local thermal expansion caused by warming up due to the energy lost by particles crossing the material. The aim of the experiment is to measure the amplitude of the fundamental longitudinal vibration at different temperatures. We report on the results obtained down to a temperature of about 4 K, which agree at the level of about 10% with the predictions of the model describing the underlying physical process., Comment: RAP experiment, 16 pages, 7 figures
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- 2005
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5. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging
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Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., Barile L., Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, Barile, L, Lazzarini E., Lodrini A. M., Arici M., Bolis S., Vagni S., Panella S., Rendon-Angel A., Saibene M., Metallo A., Torre T., Vassalli G., Ameri P., Altomare C., Rocchetti M., and Barile L.
- Abstract
Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be consider
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- 2022
6. A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes
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Altomare, C, Bartolucci, C, Sala, L, Balbi, C, Burrello, J, Pietrogiovanna, N, Burrello, A, Bolis, S, Panella, S, Arici, M, Krause, R, Rocchetti, M, Severi, S, Barile, L, Altomare, Claudia, Bartolucci, Chiara, Sala, Luca, Balbi, Carolina, Burrello, Jacopo, Pietrogiovanna, Nicole, Burrello, Alessio, Bolis, Sara, Panella, Stefano, Arici, Martina, Krause, Rolf, Rocchetti, Marcella, Severi, Stefano, Barile, Lucio, Altomare, C, Bartolucci, C, Sala, L, Balbi, C, Burrello, J, Pietrogiovanna, N, Burrello, A, Bolis, S, Panella, S, Arici, M, Krause, R, Rocchetti, M, Severi, S, Barile, L, Altomare, Claudia, Bartolucci, Chiara, Sala, Luca, Balbi, Carolina, Burrello, Jacopo, Pietrogiovanna, Nicole, Burrello, Alessio, Bolis, Sara, Panella, Stefano, Arici, Martina, Krause, Rolf, Rocchetti, Marcella, Severi, Stefano, and Barile, Lucio
- Abstract
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific IK1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents.
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- 2023
7. 20451. UN CASO DE UNA POLIRRADICULOPATÍA SUBAGUDA DE CAUSA INHABITUAL
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Angerri Nadal, M., Valín Villanueva, P., Hernández Pérez, G., Teixidor Panella, S., Muñoz Vendrell, A., Martínez Yélamos, A., Povedano Panades, M., Solanich Moreno, X., Rocamora Blanch, G., Antolí Gil, A., Martínez Yélamos, S., Arroyo Pereiro, P., and Marco Cazcarra, C.
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- 2024
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8. Protective role of cardiac progenitor cell-derived-exosomes in a new human model of ageing-induced cardiac dysfunction
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Lazzarini, E, primary, Lodrini, AM, additional, Bolis, S, additional, Arici, M, additional, Vagni, S, additional, Panella, S, additional, Rendon Angel, A, additional, Torre, T, additional, Vassalli, G, additional, Ameri, P, additional, Altomare, C, additional, Rocchetti, M, additional, and Barile, L, additional
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- 2022
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9. The wound and the leg amputation of Giovanni dalle Bande Nere (1498-1526): life and death of a mercenary captain of the italian renaissance
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Ventura, Luca, FORNACIARI, G., Saragoni (Forlì), L., Ercolani (Forlì), G., LICATA, M., RUSPI, A., IORIO, S., LARENTIS, O., TESI, C., BENAGLIA, P., TOSI, A, ARMOCIDA, G., RONGA, M., ROSSETTI, C., GIUFFRA, V., BARTOLOTTA, E., MILANESE, M., BOANO, R., PALLECCHI, S., SANTORO, E, BERTOLINO, S., VELLONE, V.G., BUFFELLI, F, FULCHERI, E., ALABISO, A., BRIDELLI, M.G., MAZZOTTI, M.C., FERSINI, F., PELOTTI, S., LUISELLI, D., TRAVERSARI, M., FUSCO, R., CERMESONI, B., RAVAGNAN, A., BADINO, P., DI CORCIA, T., DE ANGELIS, F., ROMBONI, M., VELTRE, V., LABARGA, C. MARTÍNEZ, RICKARDS, O., VARANO, S., CALDARINI, C., PANTANO, W., CATALANO, P., MARTÍNEZ-LABARGA, C., Rabino Massa (Torino), E., Licata (Varese), M., GUERRIERO, M., COLASURDO, F., POLLIO, A.M., PONZIO, G.V., CILLI, E., LUISELLI, D, GRUPPIONI, G., SARAGONI, L., PETRELLA, E., VENTURA, L., RIPANI, M., GAETA, R., MINOZZI, S., FORNACIARI, A., RICCOMI, G., LOMARTIRE, S., PICCHIONI, L., IOANNUCCI, M., PANELLA, S., MICARELLI, I., PAINE, R.R., TAFURI, M.A., MANZI, G., BUFFELLI, F., BONSIGNORE, A., CILIBERTI, R., Traversari (Forlì), M., Gaeta (Pisa), R., SACCHERI, P., TRAVAN, L., GOTTARDI, G.M., FOSCATI, A., FORTUNA, S., CARLI, A., PIOMBINO-MASCALI, D., BIRKHOFF, J.M., CISINI, S., DE STEFANO, F., RABINO, E., FERRARI, L., PULCINELLI, D., RULLO, D., LOMBARDI, A., METOVIC, J., PAPOLA, F., Ferrari (Asti), L., Fulcheri (Genova), E., PIETROBELLI, A., MARIOTTI, V., FUSARI, S., BETTUZZI, M., MORIGI, M.P., BELCASTRO, M.G., TONINA, E., AMARO, A., CAVALLINI1, L., COSCHINO, F., VERCELLOTTI, G., DE SANCTIS, M., ISHAK, R., ARINGHIERI, G., BRUSCHI, F., MANNINO, M., PANGRAZZI, C., GORINI, I., PAUDICE, M., BIATTA, C.M., PEÑUELA, L., and CINTI, A.
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Meeting Report ,Lecture ,Article ,Pathology and Forensic Medicine - Abstract
The tomb of Giovanni and his wife Maria Salviati at Cappelle Medicee in Florence was explored to investigate the skeletal remains. Anthropological and paleopathological examination defined: age at death, physical constitution and activity, skeletal diseases. The stump of the right leg was studied macroscopically, under stereoscopic microscope, at X-ray and CT scans, to detect type of injury and level of amputation. The study of the skeleton of Giovanni revealed that he was a vigorous man, 1.78 m tall, with an athletic body, estimated skeletal age of 25-30 years, medium-sized skull, narrow nose and great skull capacity (1494 cc). His well-developed upper limbs muscular insertions (deltoid, great pectoral, great dorsal, biceps, forearm muscles) and thigh muscles confirmed his great physical strength and robusticity. Strong hypertrophy of rotator cuff, great dorsal, teres minor and anconeus insertions were all present, as well as gluteal insertions to the femur, confirming he was a highly skilled horseman. The presence of numerous Schmorl’s hernias and a wedge partial collapse, with right spondylolysis, of the fifth lumbar vertebra, revealed that Giovanni had carried heavy loads since adolescence due to horse-riding and body armor. Diffuse bilateral enthesopathies were found at the clavicular insertions of deltoid and pectoralis major, as well as at the small trochanter (psoas muscle). Skeletal markers left by habitual horseback riding were all present: exostoses and ovalization of acetabula, hypertrophy of femoral rectum muscle, strong hypertrophy of the femoral biceps, great adductor, small and great gluteus, Poirier’s facet. Paleopathological investigation showed the aftermaths of several injuries: fractures of nasal septum and proximal third of the left humerus, injury from blade affecting right ulna and radius and swelling of the posterior surface of the right tibia, with underlying osteomyelitic focus in reparative phase, as well-documented on CT. The amputation level was exactly assessed: the tibia was sawn immediately below the proximal half of diaphysis and only the lateral portion was surgically treated with an horizontal cut. Only oblique splitting was found at the medial site of the tibia. At stereoscopic microscope, surgical section revealed a marked proliferation of endosteal callus, due to a previous harquebus shot injury occurred about one year before the death. Distal extremity of fibular fragment showed an oblique splitting and a horizontal cut, with no sign of reparative process in the medullar canal. Considering the morphological aspect of the tibial and fibular injury, it was due to a cannonball from a falconet of caliber 6-7 cm, as written by Benedetto Agnello in the same day of injuring. The limb had been severely damaged by a traumatic hemi-amputation when surgeon Abramo performed the intervention, consisting in a simple completion of the amputation and regularization of proximal fragments. In conclusion, paleopathological investigations lead to exclude the hypothesis of an amputation above the knee, since the surgeon Abraham performed the procedure as best as he could in conformity with surgical knowledge of that period., Biomechanical and kinesiological reasoning allow us to investigate traumas in Paleopathology. The focus of our analysis is to reconstruct pathomechanics, treatment and gait of a subject from the Late Medieval femur, which presents an important bone callus (1). The femur was discovered in a funerary crypt of the Sanctuary of Sacro Monte (Varese, Northern Italy), an important archaeological context inserted into the UNESCO heritage since 2003. The femur was studied with computer tomography and the reconstruction of the static and dynamic fictional outcomes of the lesion was performed by the Observation Gait Analysis (OGA). The OGA is the computerized analysis of the gait. This technique permits to observe movements of each articulation in the space, the posture and the gait underlining a movement strategy. The femur presents an important callus at the middle third proximal of the shaft. The fracture is oblique and caused by a direct trauma probably associated with occupational activities. The alignment of the segments in the frontal plane leads us to assume that the fracture was treated and the femur was immobilized with splints. The use of OGA allows us to understand the subject’s kind of gait after healing. Our analysis demonstrated that there was no reduction in bone mass. The deposition of new cortical bone near the fracture determines that the individual has gradually resumed loading the leg and was walking although with significant effects on posture and movement., In 2008, archaeological excavations carried out in the inner courtyard of the former Jesuit College of Alghero brought to light the San Michele cemetery. Characteristic of the site are some burial trenches, narrow and long pits containing the remains of 10 to 30 individuals, and some multiple tombs, which can be related to the plague epidemic that ravaged the city in 1582-83. The present study is focused on the demographic analysis of the 16 trenches containing 185 individuals and of one multiple tomb (T.141) with 14 individuals. In the case of the trenches it was possible to determine the sex of 178 individuals: 37 are males (20.7%), 53 females (29.8%) and 88 of undetermined sex (49.5%). As for the first two groups, 35.6% of individuals has an age comprised between 20 and 29 years; the two age ranges 30-39 and 40-49 years present the same percentage (25.6%), 8.9% are aged between 17 and 19, and finally 4.4% are over the age of 50. The undetermined sex category is represented by 81 subadults and 7 adults. As for the subadults, the most representative age group is that between 7 and 12 years old with 39.8%, followed by the 23.9% between 13 and 19 years, 18.2% between 2 and 6 years, and finally, 10.2% between 0 and 1 years. The multiple tomb 141 includes an adult individual (20-29 years) of undetermined sex, a woman of about 17 years and with a 35-week fetus in her womb, and finally 12 subadults in an age range between 0-1 years (21.4%), 2-6 years (7.1%) and 7-12 years (50.0%). The cemetery of San Michele presents some similarities with the French cemetery of Martigues struck by the plague in 1720. Also in this cemetery this type of trench burials was found, 5 in this case, with 199 individuals. The comparison between the paleodemographic curves for both cemeteries evidences a similarity of the mortality trend. The difference between normal and catastrophic cemeteries, related to a severe epidemic event, consists in the fact that while in the former there is a greater presence of infants and elderly, in the latter there is a certain homogeneity of mortality, proof of the fact that the plague kills in a random way and therefore all individuals present the same risk of death., Ossification of spinal ligaments can persist on skeletal remains requiring a differential diagnosis between diseases that can lead to spinal column ankylosis. The most relevant diseases that can lead to this condition are represented by ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). The differential diagnosis between these two conditions is discussed in two cases of our observation. Case n. 1: Policastro Bussentino, US 112 - The burial (US 112) was found in the convent of San Francesco in Policastro Bussentino, during an emergency excavation carried out in 2015. The skeleton on a stratigraphic basis is dated between 1846 and 1892. The skeleton is affected by the fusion of 12 vertebrae of the vertebral column, from the fusion of some costovertebral joints and of the sacroiliac joints. Case n. 2: Turin, Collection Marro, skeleton n.16809 - The skeleton belongs to the Egyptian Collection of the Museum of Anthropology and Ethonography of the University of Turin. It was collected during the archaeological campaign at Gebelein (Upper Egypt) in 1920 and dates back to the First Intermediate Period (2150-1990 BC). In this case, the pathology involves only the vertebral column in which the fusion of numerous vertebrae is found. AS is a progressive inflammatory disease of unknown etiology primarily affecting the diarthrodial joints of the spine, the costovertebral joints and the sacroiliac joints and usually begins in the second or third decade of life. First it affects the lumbar spine and the sacroiliac joints and progressively ascends until the entire spine and all costovertebral joints are affected. The result of this ankylosing process is the rigid, so-called bamboo spine with loss of its physiological curvatures. DISH is an ossifying diathesis producing ankylosis of the spine due to ligament ossification without intervertebral disk disease. It is not a true arthropathy because neither cartilage nor synovium are involved. It is rarely detected before the age of 40 years and the cause is unknown. The two pictures macroscopically can be confused because both involve the spine with ossification and ankylosis of it. The differential diagnosis on skeletal remains can be based on extimated age and sex and on the elements involved. AS occurs in the second or third decade of life and mainly affects men. DISH, instead, appears not before the fourth decade of age. DISH only affects the spine, while ankylosing spondylitis also affects the cost-vertebral joints and the sacro-iliac joint. The ligaments involved in the fusion of the spine are different in the two cases. DISH does not affect the intervertebral discs unlike AS which instead involves them and thus has a total fusion of the vertebral bodies. Although DISH and AS manifest in a similar manner, they are separate diseases. Both pathologies are quite common in mild and initial forms, but are rather rare in the full-blown, severe forms, which involve the whole spine. This topic appear poorly covered both in paleopathological and clinical literature, mainly consisting in small series and case reports. As a consequence, a wide inter-individual variability is present and only rarely an accurate report of the different involved ligaments is provided. In most of the cases the description is limited to a generic attribution to spinal ligaments. Differential diagnosis may be challenging if limited to anthropological examination of the skeletal remains and further radiologic and genetic tests are necessary to confirm our findings., The object of this study is the so-called “green mummy” of Bologna, a naturally mummified body that was found in the basement of an ancient mansion in Bologna in the 1920s of last century. The hard and soft tissues of the body are green for the most. They were analyzed by FTIR spectroscopy with the aim to gain information about the biochemical degradation process, to explain both the origin and the nature of the green color and to understand how it affected the body’s preservation. The corpse was found in a copper or bronze cist that, at the time of recovery, was closed with a lid but broken at the base. It is reasonable to assume that the body had undergone the processes of putrefaction, liquefaction, skeletonization and mummification within the container. Probably, the semi-fluid mass of water and decomposing substances came out from the cist through the break at its base; therefore, the not yet putrefied tissues exposed to the atmosphere of the basement, desiccated and mummified. The acidic liquids originated by the decomposition caused the container corrosion, favouring the release of copper ions. Metal ions both inhibited the enzymes responsible for chemical reactions in the early stages of the decomposition process and acted as biocides of microorganisms involved in decomposition. FTIR analysis of soft tissues, with and without green color, showed that tissues lacking the green patina were the best preserved revealing the protein structure only minimally deteriorated, contrarily to what was observed in green areas. We have hypothesized that copper ions might have caused the decarboxylation of the RCOO group of polypeptidic backbone favoring protein degradation. Therefore, copper did not favor the mummification process, which was probably due to the environmental conditions, such as the low temperatures typical of the basement and the low availability of oxygen. Due to the known biocidal action of copper ions, we assume that copper ions might have damaged dead tissue cells in the same way they damage the cell membrane of microorganisms with which it comes into contact, causing their death. After the body decomposition liquids came out from the container, copper corrosion products precipitated as copper compounds giving the remains the green color. On the soft tissues two mineral forms of copper have been found: copper carbonate and copper phosphate called malachite and sampleite. Also, FTIR analysis of bones revealed that copper did not contribute to tissue preservation. The measured mineralization index showed the alteration of both collagen and hydroxyapatite of colored bones unlike the colorless ones. A compound known as pseudomalachite was identified in the green bones, a form of hydroxyapatite where copper replace calcium. This substitution is responsible for the unusual green coloration of the bones., The new paleoradiological investigations carried out on the Egyptian mummified human remains, a head, a left hand and foot, housed in the Civic Archaeological Museum of Erba (Como, northern Italy), allowed us to acquire comprehensive digital images and to study the anthropological and paleopathological data of the subjects. The first macroscopic investigation revealed the presence of blue-glazed Faience tubes, adherent to the dorsal wrappings of the foot. This custom was particularly attested in the 26th dynasty, even if it appeared already from the 21st dynasty and seemed to continue until the Ptolemaic period. The tomographic analysis revealed the non-compatibility of the three mummified parts to a single individual, based on the different degrees of bone development and degeneration. The radiological investigation allowed us to acquire data on the embalming techniques applied, and on the health status and pathological conditions of the head. In particular, the parietal bones of the cranium exhibited two symmetrical areas of thinning and resorption of the outer table, which suggest a case of “biparietal thinning”, also known as “biparietal osteodystrophy”. The areas involved are well-circumscribed and elliptical in shape, localized between the obelion and the superior linea temporalis. Macroscopically, these areas are noted as slight depression and flattening of the outer cortical layer. The CT imagings also revealed the mature age of the individual, which, according to several studies, is compatible with this finding. A research in the literature, showed a prevalence of this condition in Egyptian individuals, associating it with different definitions and causes. Although the etiology of this affection is still not well-known, here the embalmed head of an elderly individual revealed the presence of biparietal affection, with thinning and resorption of the outer table, adding additional evidence of this finding in an Egyptian subject., The GEDEON project will allow us to broaden the knowledge about the human adaptation against changes in nutritional resources consumption. The main purpose of the project is to investigate the putative role of selective pressure that may have acted on specific genetic markers linked to changed dietary conditions. In order to reach this topic, the project aims to connect the scientific evidence obtained through osteological studies of the ancient remains dating across the major nutritional transitions, with the evaluation of genetic markers involved in metabolic pathways that may have been affected by nutrient bio-availability. The whole genome analysis of ancient selected skeletal specimens will be sequenced to compare the data obtained with those from extant people suffering of nutritional impairments, whose information on dietary requirements is available. Known polymorphisms that are classically referable to diet-derived homeostatic alterations will be selected, such as rs2066844, rs2066845 and rs2066847, whose association with inflammatory intestinal diseases (IBD) is well known. Other variants mapping on NOD2 gene (for example rs2066843 and rs2076756) will be focused, but they will represent only the starting point for the identification of causative molecular pathways modifiers. Furthermore, the markers with a well-known association with alterations such as celiac disease (CD) and primary hypolactasia (PH) will be also considered: PTPN2 and IL18RAP loci as well as various HLA system factors and the LCT gene will be primarily evaluated. This shortlist selection will constitute the beginning for the identification of several new markers to shed light on human genetic adaptation to the changed environmental conditions including the nutritional requirements., The application of the next generation sequencing techniques to the study of ancient DNA represents an outstanding improvement for clarifying complex scenarios related to genomic-based physio-pathological conditions, whose identification in ancient remains can be tricky. Indeed, the sole presence of osteological markers could be misleading for proper diagnosis due to the non-specific nature of such lesions. A thorough molecular evaluation has been performed on a skeleton of an adult woman dating to the Roman Imperial Age. The erosive and osteolytic markers located in the tarsal bones have led to hypothesize that she probably suffered from gout. In an attempt to integrate the differential diagnosis based on osteological data, whole genome sequencing analysis was performed. The bioinformatics pipeline identified the presence of two variants in the TSC2 gene, that is known to be associated with a rare genetic disorder, the Tuberous Sclerosis Complex, featured by signs that could be shared with those due to gouty arthritis. The application of these ultimate molecular techniques surely represents a successful diagnostic tool for the identification of genetic related disorders that could be only hypothesized in ancient times., Domenico Petruccelli (Raffaele da Sant’Elia a Pianisi), servant of God, was born in Sant’Elia a Pianisi (Campobasso) in 1816 in a family of honest and wealthy peasants. He lived in different convents between Puglia and Molise. Wherever he went, he won the esteem and veneration of everyone, so much so as to be called the “Holy Monk”. He died in the convent of Sant’Elia a Pianisi in 1901. In the same convent another famous monk arrived in 1904 fr. Pius from Pietrelcina (better known as Padre Pio), here the young monk breathed the aura of holiness left by the Holy Monk who died a few years earlier, drawing strength and inspiration. A first exhumation had been performed in 1934 and the skull was placed in a metal case. In 2017, 200 years after his birth, during the second exhumation and canonical recognition of the mortal remains, the skull was in good condition of conservation. It was covered in a thin layer of yellowish-white powder and traces of deteriorated fabric which formed part of the inner lining of urn. Cleaning operations The skull was cleaned. During this operation, we proceeded to collect in a container of numerous fragments adhered to the outer and inner surface of the skull. Consolidation operations The skull was impregnated with a thin protective membrane consisting of a very thin film of an acrylic resin (Paraloid B72TM) which protects it and consolidates its most delicate and fragile parts. Paleopathological study The alterations and lesions found are: in the left orbit, two holes (of undetermined origin) in the left parietal and temporal bones, in the right parietal bone, at the base of the skull, the jaw is absent. Attribution of sex We highlight a series of morphological findings characteristic of the male sex. They are: protruding glabella and sloping forehead; Rounded, wide and thick super-margin; Wide zygomatic arch that extends beyond the external acoustic meatus; Mastoid process robust, big and verticalized; Necked crest marked, wrinkled and very evident. Diagnosis of age Coronal, sagittal and lambdoidal sutures were considered, in accordance with the criteria of Acsàdi and Nemeskèri (1970) modified by Masset (1989). The endocranial closing index can be estimated at around 4, so the subject’s age is between 50 and 80 years, according to the known age of Father Raffaele of 85 years at the time of death. Craniometry The craniometric assessments carried out highlighted: a small, rounded, long, narrow, medium-high skull with rounded sagittal contours, oval and angular orbits, mean interorbitary distance, narrow nasal opening. All these characteristics allow us to state that the skull belonged to a Caucasian subject. Histological examination The fragments examined were composed of human organic material. These are extensively necrotic and rotten tissues. An important result has been achieved with the finding in the histological findings of many fungal hyphae, better highlighted with histochemical stains PAS and Grocott., Historical information related to the life of St. Mercurialis is very scarce, everything we currently know, we owe to its legenda, is contained within the manuscript Casanatense 718 dating to the 12th century. The only certain historical information concerns the ordination of one of his successors, Grato, which took place in Ravenna during the 5th century. The relics of St. Mercurialis, preserved inside the homonymous abbey, in the Cathedral of Santa Croce and in the Santissima Trinità church, during 2018 were object of the sixth canonical recognition, necessary to verify the state of conservation of the bones. Preliminary studies were performed by direct anthropological and radiological analyses by CT scan, FTIR analysis, ancient DNA and radiocarbon dating. St. Mercurialis, was about 1.60 meters tall, the age at death is 45-50 years, and he was not particularly robust, even if marked by repeated musculoskeletal stress probably linked to habitual activities such as walking and weightlifting. He suffered from osteoporosis and perhaps had some discomfort with the shoulder girdle. He had a deviated nasal septum from birth, a condition that perhaps caused him disorders such as sinusitis. He did not suffer from osteoarthritis and he had no particular indicators about deficiencies suffered during the first and last period of life. Analyses did not reveal indicators due to traumatic events and probably did not die by strangulation, as the hyoid bone was intact. FTIR analysis was carried out on the brown substance that partly covered the lower skeleton district, shows the typical spectrum of clayey materials. The characteristic bands reveal the presence of aluminum and silicon in greater quantities, and of other elements in smaller quantities. The clays constituting the soil can therefore be considered essentially illites containing kaolinite, smectite and quartz. This aspect confirms the numerous historical information concerning the floods suffered by the abbey. A patina that covered some bones was also detected. The obtained spectrum presents the typical absorptions of the vibrations of the hydrocarbon radicals CH2 and CH3, in addition to the intense absorption typical of the C-O-C group characteristic of carbohydrates. The characteristics of the spectrum therefore seem to be typical of a methylcellulose preservative. Radiocarbon dating and accelerometry mass spectrometry (AMS) dated the relics to the I-III century AD, an interesting date that is chronologically before the only historical indication we have about the life of St. Mercurialis and which collocates his episcopate into the first stages of evangelization of the Emilia Romagna Region. The preliminary analyses of ancient DNA were targeted on the hypervariable region 1 (HVR-1) of the mitochondrial DNA (mtDNA) and on Short Tandem Repeats (STRs) of the Y-chromosome and highlighted a rather pronounced diagenesis of the DNA. The subsequent analyses will be targeted to the capture of the entire mtDNA, coupled with next generation sequencing., Andrea was a Catholic priest and a member of the Order of Saint Augustine. He was born to a modest family in the village of Mascioni (northern borders of L’Aquila province) and as a child he worked as a shepherd. Around 1417 he met Augustine from Terni, Prior of the Augustinian convent in the near Montereale, and asked to enter their ranks to be ordered as a priest at the age of 25. He earned a bachelor and master’s degree in theology, becoming professor in Siena (1443), and Provincial Prior of the Umbria region. He also served as a travelling preacher in Italy and France, reforming several Augustinian monasteries in Umbria. He died on 18 april 1479 in Montereale and, according to hagiographies, his body was exposed without balsams in the conventual church for 30 days, giving off sweet odor and performing miracles. Subsequently, it was placed in the Choir until 1568, when it was displayed beneath the main altar. His beatification was celebrated by Pope Clement XIII on 18 february 1764. In 1787 the body was translated into a newly built repository, inside the new chapel dedicated to him. Documented Canonical Recogntions took place in August 1786, July 1943, June 1961, and between June and July 1989. The last was performed by one of us (MR) and the late professor Giulio Marinozzi. External examination of the body allowed to recognize a partially skeletonized mummy belonging to an old male subject (more than 70 years of age at death) and measuring 164 cm in length. The face was almost entirely covered by mummified skin, with traces of hair in the perioral region, chin, cheeks and anterior neck, according to devotional representations of the Blessed as a bearded elder. Soft tissues of forearms, hands, legs and feet appeared in a good preservation state. A large bone defect was observed in the occipital squama. Large skin cuts were observed in the anterior neck and left hemithorax. The ventral portions of the left ribs appeared cut and displaced within the thoracic cavity. Cut marks were also found on the left margin of the sternum body and on anterior branches of the pelvis. Preserved skin was observed only in the right hemithorax. No traces of internal organs were found in thorax, abdomen and pelvis. Moderate-marked osteoarthritis of the spine was noted. Unfortunately, a radiologic investigation of the body was not performed. After external examination, conservative treatment was performed. The body of Andrea revealed indisputable evidence of artificial mummification, representing the eleventh described case of an embalmed Saint or Blessed in Catholic Religion. Nine of these artificial mummies were created in central Italy (Umbria, Toscana, Abruzzo, Lazio) between the XIII and XV century. The employed evisceration procedures appear somewhat rough, without the complexity observed in other examples. It is worth to note that Montereale is located not far from L’Aquila and on the main route towards Cascia and Spoleto. The embalming of the Blessed Andrea took place only 35 years after the death and embalming of Saint Bernardino da Siena in L’Aquila and represents the second case in Abruzzo region., Liutprand, one of the greatest Longobard sovereign, was born in the early 90s of the 7th century and died in 744 at the age of about 55 years. According to the Historia Longobardorum of Paolo Diacono, he was King of Longobards from 712 to 744. The remains of King Liutprand suffered from many translations in the centuries and this is the main problem for the validation of the authenticity of the bone remains. The first grave was in the chapel of Sant’Adriano in the Longobard cemetery of Santa Maria in Pertica (Pavia). Later, in the second half of 12th century, the body of Liutprand was translated in the Basilica of San Pietro in Ciel d’Oro and located in a monumental mausoleum. New translations took place after the Council of Trento and in 1895, when the bones were placed in a niche in the floor of the church where they were found in January 2018. The bones, contained in a wooden box, appeared extremely fragmented and in a poor state of preservation. Anthropological examination highlighted the presence of bones attributable to three individuals. Most of the remains belongs to a robust male individual with strong muscular insertions, with an age at death between 40 and 50 years. There is also a second older male with strong muscle insertions, and a third adult individual of similar size. In fact, there are a pathological left tibia and some fragments of its right controlateral, and other fragments attributable to two other left tibiae. The tibia with pathological alterations presents the upper third of the diaphysis completely altered and enlarged by bone thickening due to a severe form of osteomyelitis. Bone repair is evident and the presence of a circular depression with a diameter of about 10 mm at the point of maximum thickening could represent the trace left by a pointed object that caused the perforation of the bone and the subsequent infection with osteomyelitis. The reparative process has however led to the healing of the lesion before death, which should have occurred not far from the event (maximum 2 years). Imaging studies (CT and radiological) on the skeletal remains were performed at the “San Matteo” General Hospital in Pavia. 14C dating provide a range from 430 to 640 for the first subject, 600-770 for the second and 530-670 for the last male. Isotopic data show a rather high nutritional status for the time, with a varied diet rich of meat. In conclusion, currently it is not possible to accurately define the identity of the three individuals for lack of archaeological data and for the fragmentary nature of the bones. The age of the subjects, the robust constitution and the nutritional data suggest a belonging to a high social class perhaps devoted to war activity. Future molecular studies may perhaps reveal a possible degree of kinship between the individuals and clarify the identity of the subjects., Born to one of the leading families in Besançon, Jean Bassand was a French Christian monk. After his initial profession in the Augustinian house of Saint Paul, he joined the Celestines (a branch of the Benedictine Order) in Paris, and subsequently became prior in the city of Amiens. The Celestine monks of France were a self-governing province of an Italian Benedictine reform of the late XIII century that no longer exists. They had a great influence, representing one of the most prominent observant groups in France, and an inspiration for reform movements across multiple orders. Jean Bassand represented the most important figure in the French Celestine congregation between XIV and XV century, being elected provincial prior on five occasions. He made great efforts to establish new Houses in the French province as well as abroad. The English King Henry V invited him to found and direct a friary in Isleworth near Sheen (now Richmond, London), whereas Martin I of Aragon asked him to establish the congregation in Barcelona. In 1443, he went to L’Aquila by order of the Pope Eugenius IV, to reform the monastery of Santa Maria di Collemaggio. He had troubles in this task and retreated to Rome arguing that the Aquilans were “difficult men”, but the Pope sent him back until his mission was accomplished. He died in L’Aquila on 26 August 1445. His body, covered with lime to be displayed, was found intact 18 years after. Since his death the mummy of Jean Bassand used to be kept in the Basilica of Collemaggio. After the major earthquake that struck down the city in 2009, his remains were recovered from the church to be kept in a secret location. Recently, an inspection of the body took place as a preliminary step of a forthcoming Canonical Recognition. The mummy appeared still fully dressed, with face and hands uncovered. The skin surface was extremely well preserved, and oblique illumination disclosed multiple, round, well-circumscribed plaques on the forehead, cheeks, and upper lip. Careful examination of the digital pictures enabled us to recognize at least 19 lesions. From a modern clinical viewpoint, the facial skin eruption of Jean Bassand meets most of the diagnostic criteria for multiple seborrheic keratoses. The age at death and the lifestyle of the Blessed, with frequent, long-distance travel under severe conditions, are fully compatible with this diagnosis. It is well known that male sex, increased age and sun-exposure may predispose individuals towards the development of these lesions. This case might represent the first ancient seborrheic keratosis described in the literature, although further analyses (external examination, computed tomography, histology) are needed to confirm the diagnosis. Advanced investigation methods might also enable us to understand if an ancient case harbours the same genetic mutations detected in modern patients. In this particular case, the treatment of the corpse with lime referred to in the ancient literature may have preserved the skin lesions by dehydration., This study presents the skeletal evidence for scurvy among 22 juveniles from the Longobard necropolis of Selvicciola, Italy (VII-VIII centuries AD). The paleopathological analysis revealed a combination of bilateral porous and proliferative bone lesions affecting the orbital roof (i.e., cribra orbitalia), the cranial vault (i.e., porotic hyperostosis) and some specific areas of the entire skeleton (i.e., sphenoid, hard palate, and scapula). This pattern is typical of infantile scurvy (Geber & Murphy, 2012). The investigation also revealed a bone tissue resorption of the anterior and lateral surface of thoracic and lumbar vertebral bodies and rib lesions in 17 of the 22 juveniles that showed signs of scurvy. This kind of skeletal manifestation associated with endocranial alteration and diffuse periosteal new bone formation (PNBF) is often linked to atypical or early-stage tuberculosis (Spekker et al., 2012). Our assessment suggests that the diet in Selvicciola was mainly deficient in vitamin C, causing scurvy. Among other problems, this might indicate poor sanitary conditions and further factors related to local environment and general state of health. Consequently, scurvy may have reduced the immune resilience of the juveniles leading to the development of TB in many of them (Miladinović-Radmilović & Vulović, 2015). Additional assessment via isotopic studies of the Selvicciola burial collection (Tafuri et al., 2018) indicates that the consumption of animal proteins in their diet was quite high. Hence, TB may have originated as Mycobacterium bovis (Roberts & Buikstra, 2003), coming from dietary consumption of infected animals. The preliminary macroscopic investigation of these subadult skeletons reveals lesions that suggest a complicated relationship among several factors influencing the health of these children. Diet, infection and lack of vitamins may have contributed to the poor health and death of these juveniles. Hence, showing a complicated situation in which, these children lived and dead in. This anthropological work illustrates how paleopathology can be used to interpret the health status of individuals of past communities even when the lesion evidence suggests multiple causal factors associated with death., The Institute of Clinical Pathology currently keeps the autopsy registers from 1891 to the present; the oldest one consists of some volumes in which the protocols and the related diagnoses were written by hand; for each case, a succinct clinical history preceded the external examination. The case presented here concerns obstetric pathology related to maternal post-partum death due to uncontrollable bleeding. The autopsy was carried out in 1892 on a woman suffering from rickets with scant muscular masses; the autopsy was performed 37 hours after the patient’s death. At that time (specifically from 1886 to 1905) the Director of the Unit of Clinical Pathology was Professor Vincenzo Brigidi and the autopsy room was situated near Pammatone Hospital, which was built in the district of Portoria and almost five centuries earlier, in the fifteenth century. This was the main hospital in Genoa, and played a fundamental role in local public health; the whole institute consisted of a single autopsy room. Full-blown or paucisymptomatic rickets was common in the Italian population of the nineteenth century and the first half of the twentieth century. The high incidence of this disease was due to deficiency factors or chronic nutritional stress, which led to forms of pseudo-rickets or latent rickets; this general situation required strict supervision of pregnant patients in order to avoid fatal intra-partum accidents both in the mother and in the foetus. Moreover, it is known that the skeletal lesions typical of rickets can seriously worsen the classical pattern of common brachipelvization, resulting in more serious pathologies. Anthropologically, brachipelvization and the evolution to the erect position constitute a peculiarity of our species. Over the centuries, obstetrics has developed complex studies for the evaluation of the pelvis and in particular, for the study of planes, axes and obstetric conjugates. In the nineteenth century and in the first decades of the twentieth century, pelvimetry was carefully practiced in obstetrics to monitor the pathological conditions of the pelvis. The management of postpartum haemorrhage was less theoretically developed and, in obstetric practice, was also represented a frequent cause of maternal death. In the case presented, therefore, obstetric procedures, such as sutures of the cervix of the vagina and the use of the so-called iron perchloride as a haemostatic cauterant, were used to stop bleeding. Ferric chloride is an iron salt (hence it is wrong to call it acid, as it is wrong to call it perchloride). The haemostatic action of the latter has been known for a very long time, but owing to its caustic action, which deeply manifests itself in the tissues, it has been absolutely abandoned in modern obstetric practice. Indeed, the report reveals that ferric chloride gave the tissues inside the uterus a leathery consistency, without - however - managing to save the mother’s life., The typical modern native from Trieste is tall - they are the tallest among Italians -, over 65 years old - Trieste has the highest seniority index in Italy - and loves spending time at the seaside or eating out with friends (no statistic data are available but you can witness that with a day trip to the city!). A group of 41 individuals who lived in the Early Middle Ages in Tergeste (the modern Trieste), seems to have a lot in common with the modern inhabitant of Trieste: they were tall (average Trotter and Gleser stature for male and female are 174.2 cm and 163.2 cm, respectively) and most of them were over 55 yeas old at death (more than 50% of adult males and 50% of adult females). Moreover, some of them spent a significant amount of time in the sea, which can be seen by the auditory exostosis in males and high frequency of third distal tibiae and fibulae periostitis in adult mature females – findings suggestive of a long time spent in the sea water looking for clams. Medieval archaeological layers in Trieste show plenty of shells. These people also loved eating: the four eldest male skeletons show marks of DISH, a pathology clearly associated with metabolic disorders. One of them may have died of suffocation caused by a small-size herbivore distal humerus epiphysis showing clear signs of slicing – a morsel of stew – found on C5/C6. Talking of skeletal remains, this diagnosis can be only a suggestion; nevertheless, dysphagia leading to suffocation in the elderly is a classic. These people were buried out of the walled circle of the ancient Tergeste and not so far from the Madonna del Mare, an early Christian Basilica built in the V/VI century, on the site called Domus Mariae. In 3 out of a total of 21 tombs (the number is low because of the overlapping of different bodies), we find a skull placed in a ritual position close to the left ankle of the body. The following are the combinations found and the age at death in each of these burials: female skeleton aged 30-40/skull of child aged 4; male skeleton aged 50-60/skull of female aged more than 50; male skeleton aged 30-45/skull of male aged more than 50. In the last mentioned tomb, besides the skull to the left of the ankle there are two other skulls: one between the femora, belonging to a man aged about 20-25, and the other one to the left of his skull, belonging to a child aged about 9. The skull connected to the buried skeleton presents a trepanation probably made by scarnification: an oval hole of about 17 mm x 12 mm, on the left parietal bone. The lesion edges clearly demonstrate survival after trepanation, possibly not longer than 1 or 2 months. In fact, in the inner table, near the hole, some coral-like new bone lesions reveal a meningeal involvement. Neither the skull nor the other bones reveal traumatic lesions; we found only a sternal foramen, the lack of fusion of the transverse foramens of C2 and a osteochondritis dissecans of the right capitellum., In the Middle Ages few examples of forensic medicine had appeared, even if imperfect and sporadic, in the field of healthcare art. In the Renaissance they took on greater consistency and framed themselves better in more defined limits. The two reports presented here are part of a trial against Jews in the city of Trento in 1475. This work takes into consideration what happened, the historical period, the trial and the sentences, and the subsequent historical revision. The study of these reports also analyzes the guidelines available at that time., To understand a disease of the past, historians need to distance themselves from today’s epistemological paradigm. The disease must lie within the epistemological limits in which it is explained. In Western medical texts of the past, from Hippocrates and Galen onwards, it was the sign on the patient that led to diagnosis through a deductive process. A debatable diagnosis by our criteria. It follows that the names attributed to diseases bore several meanings, also due to translations over time from one major language to another (Greek, Arabic, Latin) and moreover in relation to the authors describing the disease – physicians, authors of literary texts, chronicles, hagiographies – representatives of an inhomogeneous medical culture. This led to an acknowledgement of the limits of retrospective diagnosis with reference to the lexicon of the textual sources. A significant example regards erysipelas, which today indicates a precise bacterial disease: this term is first found in various points of the Corpus Hippocraticum, including book III of the Epidemics, in a story subsequently commented on by Galen. From the description of the signs the term is linked to different symptoms or diseases, if interpreted with our criteria. Transliterated into Latin, in mediaeval texts the term is placed under the category of the apostemata – exceedingly complex diseases or disturbances – especially after the translation of Avicenna’s Canon. The association with ignis sacer, an expression of Latin origin, in the De Medicina of Cassius Felix (5th C.) led in some cases to a semantic change, borne out by non-medical sources. Ignis sacer in fact, independently of its oldest meaning, first came into use in chronicle sources from the 11th century, to indicate “burning” epidemics, in which ergotism and gangrene in general may be recognised. Renaissance medical sources, following direct translations of Greek medical texts without mediation of the Arabic, tended in part to recover the meaning of the term erysipelas indicated by Galen. In Hoffman’s Dissertatio of 1729, albeit with due precautions, we may recognise the symptoms of present day erysipelas, although the physician’s association with Rosa and with fuoco selvatico begs consideration of the polysemy of two nosographic expressions found in “popular” culture in many areas of Europe. The aim of this presentation is to analyse the polysemy of a nosographic term that has come down to us from the Hippocratic tradition, together with its changes in meaning over time and in accordance with contexts. A paradigmatic case for highlighting the difficulty facing historians wishing to carry out a retrospective diagnosis by means of the medical lexicon., Paolo Gorini (1813-1881) was one of the first scientists who experimentedwith the“petrification” of corpses, a particular technique used to obtain an artificial preservation of bodies, which found wide application in Italy in the 19th century. This technique allowed the exact features of the deceased to be maintained and for tissue, internal organs and hair to be preserved, mostly in a state of stone hardness. This specific mechanism was based on the replacement of biological liquids with chemical preservatives obtained through intravascular injections. Paolo Gorini performed “petrification” on hundreds of specimens, onentire cadavers as well as on parts of corpses, most of which are now housed in the Paolo Gorini Anatomical Collection of Lodi. Lodi is also home to the manuscript with the two formulas used by Gorini to petrify corpses: “a sulfuric acid solution in the proportion of ten percent or an alcohol-saturated solution of mercuric bichloride and muriate of calcium in the proportion that the volume of the first is ten times that of the second”. The aim of our work is to verify the preservation status of skin that was subjected to “petrification” by Gorini. Our study was carried out on an entirely petrified body of an unknown individual held in the aforementioned collectionat Lodi. The man had been affected by a widespread bulbous-bullous infection, possibly smallpox or pellagra. A superficial fragment of skin, free of lesions, was biopsied from the latero-plantar region of the right foot. The analysis was performed using microscopic slides following the inclusion of the samples in epoxy resin, as well as by a stain with hematoxylin-eosin and Masson’s trichrome. Other sections were stained via immunohistochemical technique with anti-cytokeratin antibodies (AE1, AE3) and vimentin. The histological investigations revealed discretely preserved epithelial tissue, with a structure that is still recognizable on the tangential sections. It is possible to distinguishan easily detachable epithelium of the stratum corneum and deeper, more cohesive, layers (stratum granulosum and spinosum) in which the shadows of nuclei are still recognizable. Histochemical investigations revealed positivity for cytokeratins and negativity for vimentin. In contrast to natural or embalmed mummified bodies, historic petrified specimens have never been histologically analyzed. This first study demonstrates that the “petrification” method performed by Gorini guaranteed good skin preservation, allowing its histological, histo-chemical, metachromatic and antigenic characteristics to be maintained., Far from representing a sample of evidence without any current interest, the anatomical and pathological assemblages stored in academic structures are still a valuable scientific and cultural resource for museum collections. In fact, these findings are able to provide, through their precise historical contextualization, important data on epidemiological aspects and medical knowledge over the time. The lack of suitable places to store them and the absence of human and financial resources together with cultural and emotional barriers regarding the death, damn the biological items to the obscurity, despite attempts to enhance them through systematic activities of cataloguing, restoration, conservation and exhibition. The promotion of a newsensitivity towards these collections as well as the developmentof a network system among academic structures may promote the recovery of this biological heritage. These actions could increase the scientific value of the items as well as the the memory of the past and could consign to museums a new role of “places for the scientific reflection and the epistemological revision”. The public exhibition of the biological findings, in accordance with human dignity as well as ethical values, could be a valuable teaching resource towards the knowledge of the human body and also to promote the health awareness. The exposure of healthy organs and pathological ones –in reflecting of unhealthy behaviours and lifestyles or catastrophic natural events – may encourage a critical reflection on the culture of life. At the same time, past human stories, albeit incomplete and fragmentary, may also be an instrument of education in the culture of death and the values of solidarity. In conclusion, we suggest Museums and collections as vectors of new social relations to be shared with the “community of the living”, in order to promote acts of the highest moral value, through awareness campaigns, on the donation of the post-mortem body for study and research purposes., Pathology Museums house ancient specimens obtained during autopsies and generally used for educational purposes. The collections usually consist of dry and wet specimens showing diseases that no longer exist or with their natural course unmodified by therapies. The preservation of the macroscopic features due to the storage fluid has a great historical and paleopathological interest. In recent years, increasing attention is being paid to the study of the wet specimens by modern techniques. Ancient DNA (aDNA) has been investigated in different specimens from natural history museums, but the experience with human material is still limited. The time elapsed between death and fixation, and the chemical composition of fixation and storage fluid may irreversibly damage the DNA, thus routine techniques may result ineffective. We propose a simple and reliable approach to aDNA collection and extraction from museum wet specimens. Ten wet specimens were selected from the Pathology Collection of Turin and submitted to histopathologic re-evaluation. As the chemical composition of the storage fluids is currently unknown, pH value was measured in each specimen. Four cases representative of different classes of pH were submitted to DNA analysis by conservative sampling. Tiny fragments of tissue were frozen at -20°C to obtain sixty 10 mm-thick sections, collected in microtubes containing 1 ml of digestion solution (75 mM NaCl, 10 mM tris, 0.5 mM EDTA, pH 8.0) and 100 ml of proteinase K solution (18 mg/ml). The samples were incubated at 56°C for 48 h and 50 ml fresh of proteinase K solution were added for 72 h. 400 ml of solution were extracted with magnetic beads using a Roche MAGNA PURE COMPACT instrument. DNA quantity and quality were evaluated using the full absorption spectrum (220/340 nm) obtained by the Nanophotometer P 300 spectrophotometer. DNA concentration in ng/ml and absorbance ratio at 260/280 nm were calculated from 4 ml samples. The quality of DNA was also observed by electrophoretic run in 1.3% of agarose gel. In order to verify DNA integrity, short tandem repeat (STR) analysis was performed using the PowerPlex 16 HS system (PROMEGA) employed for personal identification. The cases were originally diagnosed as lymphosarcoma, uterine myosarcoma, esophageal, gastric, and rectal cancers, pancreas tumor, lung cancer, and pleural sarcoma. The range of pH values was comprised between 1.46 and 4.65. The pH value of the specimens submitted to DNA analysis was 2.56, 3.15, 4.45, and 4.65 and the revised diagnoses were necrotic lung carcinoma, uterine leiomyosarcoma, lung metastases from squamous carcinoma of unknown primary, and from uterine leiomyosarcoma. The first two samples gave negative results on both spectrophotometer and electrophoretic runs. The other two showed a low quantity of DNA (6 ng/ml; 7 ng/ml) with an absorbance ratio of 1.53 and 1.50 at the spectrophotometric analysis. The electrophoretic analysis showed a light band of DNA with molecular weight around 1000 bp in both samples. STR analysis displayed DNA fragmentation, evidenced by ladderization of the electropherograms result. The amplification of amelogenin STRs of chromosome X allowed the precise identification of one patient. It is well known that DNA is better preserved in alkaline medium, but its quantity and quality may be acceptable also in specimens preserved at pH around 4.5. Museum wet specimens may represent a valid source of aDNA to investigate genetic molecular features of ancient diseases. The measurement of pH value of the storage fluid may be useful as a screening method for aDNA preservation., Investigating multiple traumas observed in an individual or among members of an entire historic community has always been an area of great interest for paleopathologists and bioarchaeologists. One task faced by paleopathologists is related to the nature of the traumatic event. Such violent events can be accidental or intentional in origin. Intentional violence might be self-inflicted or an act from another person. Once this has been determined, discriminating between multiple injury events and a single event (with multiple fractures) is challenging. While assessing the skeletal collection from the post-classical necropolis of Selvicciola (Viterbo, Latium, Italy; 4th-8th centuries AD), an adult male burial revealed a unique pattern of healed injuries. This male (T 90/5) was buried without grave goods. His tomb is located far from the church, which is the centre of the necropolis. T 90/5 is part of a specific burial group of Longobards situated in South-Eastern funerary area (dated to later period of the 7th century AD). Of these elements we located 6 fractures. This included a well healed nasal fracture, right clavicle fracture, a right scapula fractured with healing along the entire superior body (glenoid fossa to vertebral border), left scapula with an acromion process fracture healed but unfused, a healed rib right fracture and a left femoral neck fracture (unfused). This last facture appears to have happened a few months before his death. The lower edge of the fracture on the femur is well healed with a line of 2 mm of new bone formation. Moreover, the periosteal surface under the neck shows eburnation compatible with the eburnation of the inner part of the head of the femur. The inner surface of the femoral head shows polished remodelled trabeculae lesion. Its creation can likely suggest that a pseudo-articulation between the edge of the diaphysis and the head of the femur was formed as a result of movement of the joint area after the fracture occurred. Also related to the health status of the male is the considerable state of DJD of long bones, as well as the significant evidence of vertebral OA and Schmorl’s nodes. Towards the end of his life this individual was suffering from a number of chronic problems, which produced skeletal lesions specific to biomechanics and old age. Some of this might have been influenced by the trauma experienced earlier in life. Likely, at the end his life his last fracture might have been due to osteoporosis of the femoral neck. The survival of this man testifies to community care and a high value given to human life. The variety of implications in this case-study inform us the care for this individual, that for most part of his life was a disable. Not only the injuries, but also the pain suffered had to affect his daily life. In the end, the protocol of cares was realized by the community at least two times; for the first pattern of trauma (nose, shoulders, clavicle and rib) and for the femur break., Rheumatoid arthritis is a chronic, systemic, inflammatory condition that starts from a synovitis, leading to diffuse erosions in the marginal area of joints and finally conducting to articular deformity and destruction of bone ends. The aetiology of the disease is unknown but multiple genetic and environmental factors have been linked to its development. According to clinical studies, 10-30% of cases undergo healing of lesions and spontaneous remission of the disease. Today’s approach to inflammatory diseases is conditioned by the early diagnosis, thanks to the evolution of the diagnostic methods and by the mitigation of drug therapies. In the past, the remission was entrusted only to the individual’s immune resistance. A case of erosive polyarthropathy has been discovered in an elderly male individual recovered from the medieval cemetery of San Biagio in Cittiglio (northern Italy). The well preserved skeleton was unearthed in the external area in front of the church access and, according to the archaeological stratigraphy, it dates back to a period between the 12th and the 13th century. The bone elements, following macroscopic and microscopic analysis, exhibit several erosive lesions with symmetrical distribution, affecting firstly the appendicular skeleton of the little joints of hands and feet and other larger joints, such as the shoulder, elbow and hip. The bony tissue involved by the erosions is the so-called “bare area”, in the marginal region of the joints, where the synovium membrane-lined bone is found. The diagnosis of this erosive polyarthritis is complicated by the mild expression of the lesions and by the presence of a subtle sclerotic border to some erosions radiographically observed. Next, a careful differential diagnosis was necessary to clarify the aetiology of the polyarthropathy; the skeletal distribution of the lesions and their macroscopic and radiological appearance are suggestive of a case of rheumatoid arthritis-like polyarthropathy. A hypothetical remission phase of the disease, as demonstrated by the frequent presence of smoothed borders and sclerosed margins on radiographic images, is also suggested. Co-existence of diffuse marginal lipping, joint degeneration and severe areas of eburnation, is also recorded, suggesting a co-morbidity of the erosive condition with osteoarthritis, which is compatible with the advanced age of the individual. With this medieval case, we present new evidence of the existence of erosive arthritis and, specifically, of rheumatoid arthritis-like polyarthropathy in Europe before the discovery of the Americas, entering into the long debate about the antiquity of the disease that, firstly, was considered as originating in the New World and subsequently spread to the Old World. On the basis of this and other already published cases, rheumatoid arthritis seems to have been present in Europe more anciently than was previously thought., Between 2012-2014 the Superintendence of Archaeology, Fine Arts and Landscape of Emilia-Romagna, has conducted archaeological fieldworks on a large Late Medieval cemetery (14th-16th century), which archaeological and documentary sources attribute to a Jewish context. The Laboratory of Bioarchaeology and Forensic Osteology of University of Bologna conducted an anthropological study on a sample of 130 individuals. This contribution aims to present four possible cases of venereal treponematoses (TT. 91, 136, 170, 187). Human skeletal remains of graves 91, 136, 170, and 187 were examined to reconstruct the biological profiles and to conduct paleopathological and tomographic analyses, given the presence of lesions on several anatomical districts. Cranial lesions were present on individuals from TT.91 (M, 25-35 years), 170 (M, 25-35 years) and 136 (M, 15-18 years), in which simultaneous destructive and proliferative processes (caries sicca) with focal destruction and remodeling of the external surface and diploe are denoted. Long bones of these three individuals also present osseous alteration such as gummatous osteoperiostitis, with an increased bone density and non-uniform thickening. Individual of T. 187 (11-12 years) presents a hole (3 cm Ø) located on frontal bone, whose margins are remodeled with proliferative processes both on ectocranial and endocranial sides. These lesions are likely linked to treponematosis (bacterial infection by Treponema), interpreted as venereal syphilis. After differential diagnoses, we suppose the individuals of TT. 91 and 170 were likely affected by an advanced stage of the infection, while individual T. 136 seems to have been affected by a tardive congenital form of the disease. Lesions of individual of T.187 suggest an infective origin, but poor bone preservation prevents a clearer interpretation. These cases of treponematosis, possibly linked to venereal syphilis, are relevant for paleoepidemic aspects, as well as contributing to only few Italian osteological cases dating to the same period., Spinal tuberculosis (STB) is a well-known disease in paleopathology. Paleopathologists have highlighted in the last decades some morphological criteria for its diagnosis. Commonly, we are witnessing the destruction of the intervertebral disc space and the adjoining vertebral bodies, the collapse of the vertebrae and the anterior wedging which lead to a structural kyphosis classifiable in gibbus deformity. Here we present the probable STB case of a male subject, 55 years, concealed between the 18th and the first half of the 20th century in the Franciskcan monastery of Azzio, Varese, Italy. The skeleton was found both in an optimal state of preservation and representation. Anthropological analysis was performed according to Buikstra and Ubelaker standards. Paleopathological diagnosis was conducted thanks to macroscopic, microscopic and radiographic analysis, also in order to perform the differential diagnosis. Even if STB was widely present in the last centuries in northwestern Italy, only few paleopathological cases was directly studied., Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus granulosus. The life cycle of the parasite develops in the canids, which house the adult tapeworm in the intestine, and in the intermediate mammal hosts. Humans are occasional dead-end hosts, infected by eggs ingestion via fecal-oral route. The larvae from the digested eggs penetrate the human gut wall and are disseminated throughout the body by the blood. The soft tissues involved at the level of the capillaries may host the larvae, and the hydatid cyst can develop in different organs. The liver is the first organ that the larvae encounter through the blood stream and consequently it is the most frequently involved; it is followed by the lungs and then other organs in frequency. The hydatid cyst is a fluid-filled formation that grows centrifugally and that can survive in the intermediate host for years. In 10 years, it can growth to a diameter of 15-20 cm. Inside hyaline outer membrane, a cellular germinating layer produces microcystic structures that develop scolices. The scolices pouring out of the cyst develop one or more cysts that can reach every tissue. The life cycle is completed when the definitive host feeds on organs of the intermediate host that contain fertile metacestodes. Death of the germinating layer within the metacestode produces calcification of the cyst wall in the intermediate host. Calcified hydatid cysts found as archaeological finds are generally associated with skeletal remains in the thoraco-abdominal site. In archaeological records, the presence of echinococcosis is underestimated, and the find is relatively rare for different reasons: 1) difficulty of recognition by archaeologists; 2) need of accuracy in excavation and recovery of osteoarcheological remains; 3) fragility of calcified formation in the soil. Furthermore, the taphonomic alterations can cause the translation from the original site of the calcified formation and undermine the recognition of the organ affected. In Italy there are only two archaeological samples of calcified formation, most probably of echinococcosis origin, described in the paleopathological literature: one from Siena (13th-14th centuries) and one from Abruzzo (early 20th century). In this report we describe another calcified formation found in the archaeological excavation of the monastic site of Badia Pozzeveri, near Lucca, Tuscany, for which we propose a diagnosis of CE. This finding comes from a privileged lithic coffin built on the northern side of the monastic Church of San Pietro. The grave was used in the 13th century as collective burial by the same laical family group. Calcification, associated with a female individual of about 35-45 years, was discovered in the thoraco-abdominal region. We propose the diagnosis of hydatid cyst from Echinococcus granulosus based on gross morphology, micro-morphology, and a multicomponent approach with cone beam computed tomography, SEM/EDS and stable isotope analysis., Biparietal osteodystrophy (BO), with symmetrical and bilateral thinning of the parietal bones, is a condition rarely discussed in the paleopathological literature. In the past, it has been described as a non-metric trait, anatomical variation and development anomaly. Even though the aetiology is still unknown, today it is described as a pathological condition. In many individuals it appears to be age-related, therefore it has been attributed to osteoporosis, postmenopausal and senile atrophy. Other causes could be congenital and hereditary transmission. Here, we presented a possible case of BO, detected on the remains of a 50-years-old female subject (Tomb 8) excavated in the cemeterial area of the medieval church of Sant’Agostino in Caravate (Varese). Anthropological analysis was performed in accordance with the standards proposed by Buikstra and Ubelaker. Paleopathological conditions were evaluated macroscopically and microscopically. Moreover, CT scan was carried out to investigate pathological evidences. Even if the cause of this uncommon condition is not yet well understood, the present case is highly significant as it enters into the debate upon the aetiology of the disease., Atherosclerosis and its complications represent an important health problem throughout the modern world, although it seems to have accompanied humanity since its beginnings. Important documents have been reported in mummified remains. Atheromas may undergo extensive deposition of calcium and bone metaplasia (Monckeberg’s arteriosclerosis) and persist to the disintegration of the soft tissues. A complete 45-55-years-old male skeleton, 165 cm tall, from bishop’s Palace in Ivrea (Turin) was discovered during archaeological excavation in 2016. Radiocarbon analysis dated the skeleton to 1400-1600 AD. During skeletal preparation in laboratory, an ectopic biological calcification tubular shaped (19 mm in length and 7 mm in diameter) were detected among pelvic bones. At the macroscopic examination, the finding appears as an irregular tubular calcification; in cross section, the mineralized deposits span the entire volume of the lumen and some bony trabeculae in the central space are well defined. Severe calcification of the blood vessel is supposed. Calcification along the expected course of an artery/vessel was considered to be probable atherosclerosis. In relation to the anatomical localization it is supposed to be an atherosclerotic calcification of iliac or femoral artery. The case study reports an uncommon finding of arterial/vessel calcification detected on skeletal remains of an adult male from the post-medieval period. Since the age plays an important role in atherosclerosis, we do not exclude that vascular calcifications affected arteries in many regions of the body. The presented paleopathological specimens suggest that our knowledge of risk factors and the etiology of atherosclerosis are incomplete. A chronic inflammatory burden may have played a greater role than previously considered in ancient cultures and population including upper classes of Italian Renaissance. While increasingly prevalent with age in ancient and modern cultures, a strong gene-environmental interplay is established in the development of atherosclerosis across the lifespan. While genes create the vulnerability, the environment determines when and if atherosclerosis becomes manifest clinically.
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- 2019
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10. The Alternative TrkAIII Splice Variant Targets the Centrosome and Promotes Genetic Instability
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Farina, Antonietta, Tacconelli, A, Cappabianca, LUCIA ANNAMARIA, Cea, G, Panella, S, Chioda, A, Romanelli, A, Pedone, C, Gulino, A, Mackay, A. R., Mackay, ANDREW REAY, Farina, A. R., Tacconelli, A., Cappabianca, L., Cea, G., Panella, S., Chioda, A., Romanelli, Alessandra, Pedone, Carlo, Gulino, A., and Mackay, A. R.
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Genome instability ,Chromosomal Proteins, Non-Histone ,Recombinant Fusion Proteins ,Cell Cycle Proteins ,Protein tyrosine phosphatase ,Protein Serine-Threonine Kinases ,Biology ,Genomic Instability ,Cell Line ,Mice ,Neuroblastoma ,Tubulin ,Endopeptidases ,Animals ,Humans ,Protein Isoforms ,Receptor, trkA ,Molecular Biology ,Separase ,Centrosome ,Calcium-Binding Proteins ,Cell Cycle ,Alternative splicing ,Polo kinase ,Exons ,Intracellular Membranes ,Articles ,Cell Biology ,Cell biology ,Enzyme Activation ,Alternative Splicing ,RNA splicing ,Cancer research ,Rabbits ,Signal transduction ,Signal Transduction - Abstract
The hypoxia-regulated alternative TrkAIII splice variant expressed by human neuroblastomas exhibits oncogenic potential, driven by in-frame exon 6 and 7 alternative splicing, leading to omission of the receptor extracellular immunoglobulin C(1) domain and several N-glycosylation sites. Here, we show that the TrkAIII oncogene promotes genetic instability by interacting with and exhibiting catalytic activity at the centrosome. This function depends upon intracellular TrkAIII accumulation and spontaneous interphase-restricted activation, in cytoplasmic tyrosine kinase (tk) domain orientation, predominantly within structures that closely associate with the fully assembled endoplasmic reticulum intermediate compartment and Golgi network. This facilitates TrkAIII tk-mediated binding of gamma-tubulin, which is regulated by endogenous protein tyrosine phosphatases and geldanamycin-sensitive interaction with Hsp90, paving the way for TrkAIII recruitment to the centrosome. At the centrosome, TrkAIII differentially phosphorylates several centrosome-associated components, increases centrosome interaction with polo kinase 4, and decreases centrosome interaction with separase, the net results of which are centrosome amplification and increased genetic instability. The data characterize TrkAIII as a novel internal membrane-associated centrosome kinase, unveiling an important alternative mechanism to "classical" cell surface oncogenic receptor tk signaling through which stress-regulated alternative TrkAIII splicing influences the oncogenic process.
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- 2009
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11. Cardiac dysfunction after myocardial infarction: Role of pro-inflammatory extracellular vesicles
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Biemmi, V., primary, Panella, S., additional, Milano, G., additional, Ciullo, A., additional, Muoio, F., additional, Cervio, E., additional, Pernigoni, N., additional, Moccetti, T., additional, Tallone, T., additional, Vassalli, G., additional, and Barile, L., additional
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- 2018
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12. Ecodepuration Performances of a Small-Scale Experimental Constructed Wetland System Treating and Recycling Intensive Aquaculture Wastewater
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Panella, S, Cignini, I, Mulas, G, Battilotti, M, Ceccaroli, C, Falcucci, M, Hull, V, Milone, N, Monfrinotti, M, Pipornetti, G, Tancioni, L, and Cataudella, S
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Settore BIO/07 ,History and Philosophy of Science ,Scale (ratio) ,General Neuroscience ,Environmental engineering ,Constructed wetland ,Environmental science ,General Biochemistry, Genetics and Molecular Biology ,Aquaculture wastewater - Abstract
S. PANELLA,a,b I. CIGNINI,a M. BATTILOTTI,c M. FALCUCCI,a V. HULL,a N. MILONE,c M. MONFRINOTTI,c G.A. MULAS,a G. PIPORNETTI,c L. TANCIONI,c AND S. CATAUDELLAc aLaboratorio Centrale di Idrobiologia di Roma, Ministero per le Politiche Agricole, Viale del Caravaggio, 107, 00147 Rome, Italy cDipartimento di Biologia, Universita degli Studi di Roma “Tor Vergata,” Via della Ricerca Scientifica, 00133 Rome, Italy
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- 1999
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13. MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation
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Panella, S., Marcocci, M. E., Celestino, I., Valente, S., Zwergel, C., Li Puma, Domenica Donatella, Nencioni, L., Mai, A., Palamara, A. T., Simonetti, G., Li Puma D. D. (ORCID:0000-0001-6729-6967), Panella, S., Marcocci, M. E., Celestino, I., Valente, S., Zwergel, C., Li Puma, Domenica Donatella, Nencioni, L., Mai, A., Palamara, A. T., Simonetti, G., and Li Puma D. D. (ORCID:0000-0001-6729-6967)
- Abstract
Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication. Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy.
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- 2016
14. L'infezione di cellule intestinali con il virus influenzale A promuove l'adesività di ceppi E. Coli isolati da pazienti con malattia di Crohn
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Aleandri, Marta, Conte, Maria Pia, Simonetti, Giovanna, Panella, S., Celestino, Ignacio, Checconi, Paola, Longhi, Catia, Garaci, E., Palamara, ANNA TERESA, Schippa, Serena, and Nencioni, Lucia
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- 2013
15. Distribution and chemistry (Fe, Zn, Pb, Cu, Cd, Chlorophyll a) of suspended particulate matter in Strait of Magellan: Austral Spring 1989
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FONTOLAN, GIORGIO, Panella S., Fontolan, Giorgio, and Panella, S.
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Suspended matter ,distribution ,chemistry ,chlorophyll a ,Strait of Magellan - Published
- 1991
16. MINISTERO PER I BENI E LE ATTIVITÀ CULTURALI ISTITUTO CENTRALE PER IL CATALOGO E LA DOCUMENTAZIONE La documentazione fotografica delle schede di catalogo Metodologie tecniche di ripresa
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Santopuoli, Nicola, Galasso, R., Giffi, E., Morelli, C., Panella, S., Pellegrini, M., Briganti, A. P., Sattalini, F., Roberto Galasso, ICCD Elisabetta Giffi, ICCD, E.Giffi R.Galasso (a cura), SANTOPUOLI, NICOLA, R. Galasso, E. Giffi, C. Morelli, S. Panella, M. Pellegrini, A. P. Briganti, and F. Sattalini
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ICCD ,catalogazione ,schede catalogo ,documentazione fotografica ,fotografia ,metodologie ,tecniche di ripresa - Abstract
L'arch. Nicola Santopuoli viene coinvolto dall'ICCD in qualità di esperto e per conto della Scuola del restauro del Mosaico di Ravenna per la definizione delle metodologie per la documentazione fotografica delle schede di catalogo. Nel manuale operativo sono illustrate a partire dalle norme ICCD le metodologie operative per la documentazione fotografica del patrimonio architettonico e archeologico. Per le singoli sezioni si riportano i curatori: Beni storico-artistici a cura di Roberto Galasso e Elisabetta Giffi; Beni archeologici a cura di Cinzia Morelli, ICCD e Stefania Panella, ICCD, Maurizio Pellegrini, SBA per l’Etruria Meridionale; -Beni ambientali e architettonici a cura di Anna Paola Briganti ICCD; Floriana Sattalini ICCD; Nicola Santopuoli, Scuola di Restauro del Mosaico di Ravenna. L'arch. Nicola Santopuoli ha utilizzato e ampliato il manuale ed è stato utilizzato per i Corsi di formazione in Tunisia, Yemen (Memar Sit di Reggio Emilia e il Centro Regionale per il Catalogo e la Documentazione dell’IBC della Regione Emilia Romagna, Bologna). Il manuale è stato aggiornato e tradotto in arabo per corsi di formazione in Siria. (Damasco 2002).
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- 1998
17. Chemical composition and antifungal activity ofHypericum perforatumsubsp.angustifoliumroots from wild plants and plants grown under controlled conditions
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Tocci, N., primary, Simonetti, G., additional, D'Auria, F. D., additional, Panella, S., additional, Palamara, A. T., additional, Ferrari, F., additional, and Pasqua, G., additional
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- 2013
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18. Some autumn oceanographic properties of main channels of Southern and South-western margin of Tierra del Fuego. Note II- Nutrients, pico-micro-phytoplankton primary production, biomass (Chlorophyll a) and picophytoplankton cell density
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Decembrini F., Magazzù G., Panella S., Caruso G., Predanzani S., and Cignini E.
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- 1997
19. Particle acoustic detection in gravitational wave aluminum resonant antennas
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Buonomo, B., primary, Coccia, E., additional, D’Antonio, S., additional, Monache, G. Delle, additional, Gioacchino, D. Di, additional, Fafone, V., additional, Ligi, C., additional, Marini, A., additional, Mazzitelli, G., additional, Modestino, G., additional, Panella, S., additional, Pizzella, G., additional, Quintieri, L., additional, Roccella, S., additional, Ronga, F., additional, Tripodi, P., additional, and Valente, P., additional
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- 2005
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20. Seasonal variability of fractionated phytoplankton, biomass and primary production in the Straits of Magellan
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Magazzù, G., primary, Panella, S., additional, and Decembrini, F., additional
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- 1996
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21. Chemical composition and antifungal activity of Hypericum perforatum subsp. angustifolium roots from wild plants and plants grown under controlled conditions.
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Tocci, N., Simonetti, G., D'Auria, F. D., Panella, S., Palamara, A. T., Ferrari, F., and Pasqua, G.
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BOTANICAL chemistry ,ANTIFUNGAL agents ,HYPERICUM perforatum ,PLANT roots ,WILD plants ,XANTHONE ,CRYPTOCOCCUS - Abstract
The medicinal properties of the aerial parts ofHypericum perforatumsubsp.angustifoliumhave been extensively investigated, yet little is known about the chemical composition or potential uses of the root extracts. In this study, xanthone production in wild plants and plants grown under controlled conditions was investigated. Chemical analyses carried out on wild plants revealed that xanthones were mainly accumulated in the roots. We mainly detected 1,7-dihydroxyxanthone, paxanthone, 5-O-methyl-2-deprenylrheediaxanthone B, kielcorin. The roots of wild plants showed low xanthone accumulation. In the roots of plants grown under controlled conditions, xanthone accumulation was 27 times greater than that in the roots of wild-grown plants. Kielcorin was not detected in the roots of plants grown under controlled conditions. As xanthones are known for their antifungal activity, the extracts from both samples were tested against the human fungal pathogensCandida albicans, non-albicansCandidaspecies,Cryptococcus neoformans, and dermatophytes. The root extracts from plants grown under controlled conditions showed greater antifungal activity, probably correlated with higher xanthone accumulation. [ABSTRACT FROM AUTHOR]
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- 2013
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22. Control Criteria and Activities in Dumping Management in Italy
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Pagnotta, R., primary, Chiaudani, G., additional, Noce, T. La, additional, and Panella, S., additional
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- 1990
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23. Size analysis of inorganic particles in the alimentary tracts of Mediterranean mullet species suitable for aquaculture
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Mariani, A., primary, Panella, S., additional, Monaco, G., additional, and Cataudella, S., additional
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- 1987
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24. A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes
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Claudia Altomare, Chiara Bartolucci, Luca Sala, Carolina Balbi, Jacopo Burrello, Nicole Pietrogiovanna, Alessio Burrello, Sara Bolis, Stefano Panella, Martina Arici, Rolf Krause, Marcella Rocchetti, Stefano Severi, Lucio Barile, Altomare, C, Bartolucci, C, Sala, L, Balbi, C, Burrello, J, Pietrogiovanna, N, Burrello, A, Bolis, S, Panella, S, Arici, M, Krause, R, Rocchetti, M, Severi, S, Barile, L, Altomare, Claudia, Bartolucci, Chiara, Sala, Luca, Balbi, Carolina, Burrello, Jacopo, Pietrogiovanna, Nicole, Burrello, Alessio, Bolis, Sara, Panella, Stefano, Arici, Martina, Krause, Rolf, Rocchetti, Marcella, Severi, Stefano, and Barile, Lucio
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dynamic clamp, IK1, atrial myocytes, modeling, hiPSC ,Medicine (miscellaneous) ,dynamic clamping, hiPSC-derived cardiomyocytes, in silico IK1 current ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Abstract
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific IK1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents.
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- 2023
25. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging
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Edoardo Lazzarini, Alessandra Maria Lodrini, Martina Arici, Sara Bolis, Sara Vagni, Stefano Panella, Azucena Rendon-Angel, Melissa Saibene, Alessia Metallo, Tiziano Torre, Giuseppe Vassalli, Pietro Ameri, Claudia Altomare, Marcella Rocchetti, Lucio Barile, Lazzarini, E, Lodrini, A, Arici, M, Bolis, S, Vagni, S, Panella, S, Rendon-Angel, A, Saibene, M, Metallo, A, Torre, T, Vassalli, G, Ameri, P, Altomare, C, Rocchetti, M, and Barile, L
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senescence ,aging ,Induced Pluripotent Stem Cells ,Medicine (miscellaneous) ,Action Potentials ,heart ,Mice ,Sarcoplasmic Reticulum ,Induced pluripotent stem cell-derived cardiomyocyte ,Animals ,Humans ,Calcium ,Myocytes, Cardiac ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cellular Senescence ,Aged - Abstract
Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans.
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- 2022
26. DEMO Fusion Power Plant: Preliminary Sizing Analysis of Power System
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Maria Carmen Falvo, Stefano Panella, Alessandro Lampasi, Sergio Ciattaglia, Panella, S., Falvo, M. C., Ciattaglia, S., and Lampasi, A.
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Thermonuclear fusion ,Computer science ,7. Clean energy ,01 natural sciences ,Automotive engineering ,010305 fluids & plasmas ,law.invention ,power systems ,Electric power system ,power system stability ,law ,electric loads ,0103 physical sciences ,plasmas ,heating systems ,electric breakdown ,power generation ,Power-flow study ,010306 general physics ,DEMO ,tokamak ,nuclear fusion ,plasma ,Nuclear reactor ,Grid ,Sizing ,Electricity generation ,power flow ,Electric power - Abstract
EU-DEMO is a European project for the design and construction of the first nuclear reactor able to produce electrical energy thanks to thermonuclear fusion reactions. The electrical power system of this facility is particular demanding for several reasons. First, the electrical power required to operate DEMO is expected to be huge, especially in comparison to a conventional nuclear plant. Moreover, the operations are intrinsically intermittent, thus introducing specific problems in terms of energy balance and grid stability. This paper deals with a first preliminary study about the sizing and the design of the DEMO internal electrical power system, with a specific focus on the steady-state loads necessary to operate the plant. The design results are obtained and verified through a model for power flow analysis, implemented in DIgSILENT PowerFactory.
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- 2020
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27. Electrical loads and power systems for the DEMO nuclear fusion project
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S. Minucci, Alessandro Lampasi, Sergio Ciattaglia, Stefano Panella, Maria Carmen Falvo, Minucci, S., Panella, S., Ciattaglia, S., Falvo, M. C., and Lampasi, A.
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Power supply ,Control and Optimization ,Power station ,Computer science ,Power flow ,Balance of plant ,Energy Engineering and Power Technology ,lcsh:Technology ,7. Clean energy ,01 natural sciences ,Automotive engineering ,010305 fluids & plasmas ,Power systems ,Electric power system ,Plasma ,0103 physical sciences ,Power-flow study ,Electrical and Electronic Engineering ,010306 general physics ,Engineering (miscellaneous) ,DEMO ,lcsh:T ,Renewable Energy, Sustainability and the Environment ,balance of plant ,electric loads ,nuclear fusion ,plasma ,power flow ,power supply ,power systems ,High voltage ,Fusion power ,Electrical grid ,visual_art ,Electronic component ,visual_art.visual_art_medium ,Nuclear fusion ,Electric power ,Electric loads ,Energy (miscellaneous) - Abstract
EU-DEMO is a European project, having the ambitious goal to be the first demonstrative power plant based on nuclear fusion. The electrical power that is expected to be produced is in the order of 700–800 MW, to be delivered via a connection to the European High Voltage electrical grid. The initiation and control of fusion processes, besides the problems related to the nuclear physics, need very complex electrical systems. Moreover, also the conversion of the output power is not trivial, especially because of the inherent discontinuity in the EU-DEMO operations. The present article concerns preliminary studies for the feasibility and realization of the nuclear fusion power plant EU-DEMO, with a special focus on the power electrical systems. In particular, the first stage of the study deals with the survey and analysis of the electrical loads, starting from the steady-state loads. Their impact is so relevant that could jeopardy the efficiency and the convenience of the plant itself. Afterwards, the loads are inserted into a preliminary internal distribution grid, sizing the main electrical components to carry out the power flow analysis, which is based on simulation models implemented in the DIgSILENT PowerFactory software.
- Published
- 2020
28. High-resolution isotopic data link settlement complexification to infant diets within the Roman Empire.
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Cocozza C, Harris AJT, Formichella G, Pedrucci G, Rossi PF, D'Alessio A, Amoretti V, Zuchtriegel G, O'Reilly M, Mantile N, Panella S, Tafuri MA, Altieri S, di Cicco MR, Fernandes R, and Lubritto C
- Abstract
Our study explores the potential relationship between infant feeding practices and settlement complexity in the Roman Empire through high-resolution Bayesian-modeled stable isotope measurements from incremental dentine. We compiled isotopic data from permanent first molars of individuals from various Roman sites: five from Bainesse (UK), 30 from Thessaloniki (Greece), along with new carbon and nitrogen isotope analyses from four individuals from Pompeii and six from Ostia Via del Mare (AVM). Our results reveal significant inter-site variability in breastfeeding durations, ranging from 1.5 years to approximately 5 years. Notably, individuals from the highly complex urban centers of Pompeii and Thessaloniki ceased breastfeeding around or below the 2-year weaning threshold recommended by Roman physicians. In contrast, individuals from the rural site of Ostia AVM and the site of Bainesse, near the northern frontier of the Roman Empire, generally ceased breastfeeding after 2 years of age. The link between settlement complexity and duration of breastfeeding observed in our study may have resulted from adherence to medical guidelines, support infrastructures, and/or strategies to mitigate financial constraints within households., (© The Author(s) 2025. Published by Oxford University Press on behalf of National Academy of Sciences.)
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- 2025
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29. Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan-Vesicular Affinity Probes.
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Gori A, Frigerio R, Gagni P, Burrello J, Panella S, Raimondi A, Bergamaschi G, Lodigiani G, Romano M, Zendrini A, Radeghieri A, Barile L, and Cretich M
- Subjects
- Humans, Extracellular Vesicles metabolism, Peptides metabolism, Biomarkers metabolism
- Abstract
Extracellular vesicles (EVs), crucial mediators of cell-to-cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature of EVs poses challenges, as proposed markers may not be as universally present as thought, raising concerns about biomarker screening reliability. This issue extends to EV-mimics, where conventional methods may lack applicability. Addressing these challenges, the study reports on Membrane Sensing Peptides (MSP) as pan-vesicular affinity ligands for both EVs and their non-canonical analogs, streamlining capture and phenotyping through Single Molecule Array (SiMoA). MSP ligands enable direct analysis of circulating EVs, eliminating the need for prior isolation. Demonstrating clinical translation, MSP technology detects an EV-associated epitope signature in serum and plasma, distinguishing myocardial infarction from stable angina. Additionally, MSP allow analysis of tetraspanin-lacking Red Blood Cell-derived EVs, overcoming limitations associated with antibody-based methods. Overall, the work underlines the value of MSP as complementary tools to antibodies, advancing EV analysis for clinical diagnostics and beyond, and marking the first-ever peptide-based application in SiMoA technology., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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- 2024
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30. Histotaphonomic analysis of bone bioerosion reveals a regional framework of diverse deathways in the Neolithic of Southeast Italy.
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Thompson JE, Panella S, Booth TJ, Soncin S, Rajkovaca T, Belcastro MG, Isetti E, Mariotti V, Muntoni IM, Radina F, Sivilli S, Traverso A, Tafuri MA, and Robb JE
- Subjects
- Italy, Humans, Archaeology, History, Ancient, Body Remains, Bone and Bones
- Abstract
The wide diversity of Neolithic funerary practices is increasingly recognised. In Southeast Italy, recent studies have drawn attention to the co-existence of multiple ways of treating the dead within single sites and across the region. In this study, we address how such diverse deathways form a regional framework of ritual practice through histotaphonomic analysis of bone bioerosion. Samples were obtained from articulated, semi-articulated and disarticulated remains from four sites in Apulia which each presented different modes of treatment and disposal of the dead. Bone thin sections were analysed by light microscopy to characterise microstructural preservation through features including bacterial bioerosion, staining, inclusions, and Wedl tunnelling. We investigate the early post-mortem histories of individuals whose remains ended up in various states of dis/articulation and diverse depositional contexts. Disarticulated remains frequently displayed arrested or extensive bacterial bioerosion, which was also found in articulated and semi-articulated skeletons. Additionally, remains deposited in similar contexts, as well as articulated and disarticulated remains deposited together in the same context, often showed different histotaphonomic characteristics, suggesting diverse early post-mortem trajectories. As a result, we argue that Neolithic deathways in southeastern Italy incorporated a high level of diversity in the early post-mortem treatment of the body. A framework for funerary practices emerges, whereby disarticulated remains probably originated from bodies which had been buried previously and subjected to varying extents of shelter, exposure to invertebrates, and duration of burial. However, we acknowledge the ongoing research into the origins of bacterial bioerosion and the problem of equifinality, which leaves open the possibility for further scenarios of early post-mortem treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thompson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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31. Transcriptomic signature of stress-induced premature senescence in cardiomyocytes.
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Rendon-Angel A, Lazzarini E, Cascione L, Burrello J, Goshovska Y, Biemmi V, Panella S, Bolis S, Colucci M, Altomare C, Rinaldi A, Torre T, Alimonti A, and Barile L
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- Animals, Gene Expression Profiling, Cells, Cultured, Humans, Stress, Physiological genetics, Gene Expression Regulation, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Transcriptome, Cellular Senescence genetics
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- 2024
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32. Particle profiling of EV-lipoprotein mixtures by AFM nanomechanical imaging.
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Ridolfi A, Conti L, Brucale M, Frigerio R, Cardellini J, Musicò A, Romano M, Zendrini A, Polito L, Bergamaschi G, Gori A, Montis C, Panella S, Barile L, Berti D, Radeghieri A, Bergese P, Cretich M, and Valle F
- Subjects
- Cryoelectron Microscopy, Microscopy, Atomic Force methods, Lipopolysaccharides, Lipoproteins analysis, Extracellular Vesicles chemistry
- Abstract
The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one of the main obstacles for the isolation and characterization of these pervasive biogenic lipid nanoparticles. We herein present the application of an atomic force microscopy (AFM)-based quantitative morphometry assay to the rapid nanomechanical screening of mixed LPs and EVs samples. The method can determine the diameter and the mechanical stiffness of hundreds of individual nanometric objects within few hours. The obtained diameters are in quantitative accord with those measured via cryo-electron microscopy (cryo-EM); the assignment of specific nanomechanical readout to each object enables the simultaneous discrimination of co-isolated EVs and LPs even if they have overlapping size distributions. EVs and all classes of LPs are shown to be characterised by specific combinations of diameter and stiffness, thus making it possible to estimate their relative abundance in EV/LP mixed samples in terms of stoichiometric ratio, surface area and volume. As a side finding, we show how the mechanical behaviour of specific LP classes is correlated to distinctive structural features revealed by cryo-EM. The described approach is label-free, single-step and relatively quick to perform. Importantly, it can be used to analyse samples which prove very challenging to assess with several established techniques due to ensemble-averaging, low sensibility to small particles, or both, thus providing a very useful tool for quickly assessing the purity of EV/LP isolates including plasma- and serum-derived preparations., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
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- 2023
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33. A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes.
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Altomare C, Bartolucci C, Sala L, Balbi C, Burrello J, Pietrogiovanna N, Burrello A, Bolis S, Panella S, Arici M, Krause R, Rocchetti M, Severi S, and Barile L
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- Humans, Myocytes, Cardiac, Constriction, Reproducibility of Results, Induced Pluripotent Stem Cells, Atrial Fibrillation
- Abstract
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific I
K1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents., (© 2023. The Author(s).)- Published
- 2023
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34. Methodologies for Scalable Production of High-Quality Purified Small Extracellular Vesicles from Conditioned Medium.
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Andriolo G, Provasi E, Brambilla A, Panella S, Soncin S, Cicero VL, Radrizzani M, Turchetto L, and Barile L
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- Culture Media, Conditioned analysis, Filtration, Ultracentrifugation, Extracellular Vesicles chemistry
- Abstract
The development of an extracellular vesicles (EV)-based therapeutic product requires the implementation of reproducible and scalable, purification protocols for clinical-grade EV. Commonly used isolation methods including ultracentrifugation, density gradient centrifugation, size exclusion chromatography, and polymer-based precipitation, faced limitations such as yield efficiency, EV purity, and sample volume. We developed a GMP-compatible method for the scalable production, concentration, and isolation of EV through a strategy involving, tangential flow filtration (TFF). We applied this purification method for the isolation of EV from conditioned medium (CM) of cardiac stromal cells, namely cardiac progenitor cells (CPC) which has been shown to possess potential therapeutical application in heart failure. Conditioned medium collection and EV isolation using TFF demonstrated consistent particle recovery (~10
13 particle/mL) enrichment of small/medium-EV subfraction (range size 120-140 nm). EV preparations achieved a 97% reduction of major protein-complex contaminant and showed unaltered biological activity. The protocol describes methods to assess EV identity and purity as well as procedures to perform downstream applications including functional potency assay and quality control tests. The large-scale manufacturing of GMP-grade EV represents a versatile protocol that can be easily applied to different cell sources for wide range of therapeutic areas., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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35. Comparing digital detection platforms in high sensitivity immune-phenotyping of extracellular vesicles.
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Frigerio R, Musicò A, Strada A, Bergamaschi G, Panella S, Grange C, Marelli M, Ferretti AM, Andriolo G, Bussolati B, Barile L, Chiari M, Gori A, and Cretich M
- Abstract
Despite their clinical potential, Extracellular Vesicles (EVs) struggle to take the scene as a preeminent source of biomarkers in liquid biopsy. Limitations in the use of EVs origin from their inherent complexity and heterogeneity and from the sensitivity demand in detecting low to very low abundant disease-specific sub-populations. Such need can be met by digital detection, namely capable to reach the single-molecule sensitivity. Here we set to compare, side by side, two digital detection platforms that have recently gained increasing importance in the field of EVs. The platforms, both commercially available, are based on the principles of the Single Particle Interferometric Reflectance Imaging Sensing (SP-IRIS) and the Single Molecule Array technology (SiMoA) respectively. Sensitivity in immune-phenotyping of a well characterized EV sample is reported, discussing possible applicative implications and rationales for alternative or complementary use of the two platforms in biomarker discovery or validation., Competing Interests: The authors declare no conflict of interests., (© 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
- Published
- 2022
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36. De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients.
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Schiano C, Balbi C, Burrello J, Ruocco A, Infante T, Fiorito C, Panella S, Barile L, Mauro C, Vassalli G, and Napoli C
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- DNA (Cytosine-5-)-Methyltransferases genetics, DNA Methylation, Epigenesis, Genetic, Humans, I-kappa B Kinase genetics, Leukocytes, Mononuclear metabolism, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome genetics, Extracellular Vesicles metabolism
- Abstract
Background and Aims: DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications., Methods: EVs were recovered from plasma of 19 ACS patients and 50 healthy subjects (HS). Flow cytometry, qRT-PCR, and Western blot (WB) were performed to evaluate both intra-vesicular and intra-cellular signals. ShinyGO, PANTHER, and STRING tools were used to perform GO and PPI network analyses., Results: ACS-derived EVs showed increased levels of DNA methyltransferases (DNMTs) (p<0.001) and Ten-eleven translocation (TET) genes reduction. Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B, were significantly increased in plasma ACS-EVs. DNA methylation analysis on PBMCs from healthy donors treated with HS- and ACS-derived EVs showed an important role of DNMTs carried by EVs. PPI network analysis evidenced that ACS-EVs induced changes in PBMC methylome. In the most enriched subnetwork, the hub gene SRC was connected to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, BAIAP2 genes that were showed to have many molecular effects on various cell types into onset of several CVDs. Modulation in gene expression after ACS-EVs treatment was confirmed for SRC, NOTCH1, FOXO3, RXRA, DGKG and BAIAP2 (p<0.05)., Conclusions: Our data showed an important role for ACS-derived EVs in gene expression modulation through de novo DNA methylation signals, and modulating signalling pathways in target cells., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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37. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging.
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Lazzarini E, Lodrini AM, Arici M, Bolis S, Vagni S, Panella S, Rendon-Angel A, Saibene M, Metallo A, Torre T, Vassalli G, Ameri P, Altomare C, Rocchetti M, and Barile L
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- Action Potentials, Aged, Animals, Calcium metabolism, Cellular Senescence, Humans, Mice, Myocytes, Cardiac metabolism, Sarcoplasmic Reticulum metabolism, Induced Pluripotent Stem Cells metabolism
- Abstract
Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (I
NaL ) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)- Published
- 2022
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38. AIforCOVID: Predicting the clinical outcomes in patients with COVID-19 applying AI to chest-X-rays. An Italian multicentre study.
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Soda P, D'Amico NC, Tessadori J, Valbusa G, Guarrasi V, Bortolotto C, Akbar MU, Sicilia R, Cordelli E, Fazzini D, Cellina M, Oliva G, Callea G, Panella S, Cariati M, Cozzi D, Miele V, Stellato E, Carrafiello G, Castorani G, Simeone A, Preda L, Iannello G, Del Bue A, Tedoldi F, Alí M, Sona D, and Papa S
- Subjects
- Artificial Intelligence, Humans, Italy, SARS-CoV-2, X-Rays, COVID-19
- Abstract
Recent epidemiological data report that worldwide more than 53 million people have been infected by SARS-CoV-2, resulting in 1.3 million deaths. The disease has been spreading very rapidly and few months after the identification of the first infected, shortage of hospital resources quickly became a problem. In this work we investigate whether artificial intelligence working with chest X-ray (CXR) scans and clinical data can be used as a possible tool for the early identification of patients at risk of severe outcome, like intensive care or death. Indeed, further to induce lower radiation dose than computed tomography (CT), CXR is a simpler and faster radiological technique, being also more widespread. In this respect, we present three approaches that use features extracted from CXR images, either handcrafted or automatically learnt by convolutional neuronal networks, which are then integrated with the clinical data. As a further contribution, this work introduces a repository that collects data from 820 patients enrolled in six Italian hospitals in spring 2020 during the first COVID-19 emergency. The dataset includes CXR images, several clinical attributes and clinical outcomes. Exhaustive evaluation shows promising performance both in 10-fold and leave-one-centre-out cross-validation, suggesting that clinical data and images have the potential to provide useful information for the management of patients and hospital resources., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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39. Intraoperative microvascular assessment with contrast-enhanced ultrasound (CEUS) during uterine artery embolisation (UAE): a case report and literature review.
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Pesapane F, Leenknegt B, Ammar T, Panella S, Garzillo G, and Huang DY
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- Female, Humans, Treatment Outcome, Ultrasonography, Leiomyoma diagnostic imaging, Leiomyoma therapy, Uterine Artery Embolization
- Abstract
The clinical success of uterine artery embolization is determined by its endpoint. An aggressive UAE could lead to endometritis and increases the risk of unintended embolization of other organs. Conversely, an incomplete procedure may result in a poor clinical outcome due to regrowth of the fibroids. We present a case with innovative use of intraoperative contrast-enhanced ultrasonography (CEUS) for the assessment of vascularity of the targeted fibroid to determine the endpoint of embolization perioperatively. We aim to report a case of the use of intraoperative CEUS during UAE to highlight the potential pitfall of its use and provide a review of its application in the literature. Our case affirms the reported usefulness and the practical feasibility to assess the vascularity of fibroids during UAE and highlights that caution should be made by operators in cases of multiple fibroids., (© 2020. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)
- Published
- 2021
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40. Human Adipose Stem Cells (hASCs) Grown on Biodegradable Microcarriers in Serum- and Xeno-Free Medium Preserve Their Undifferentiated Status.
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Muoio F, Panella S, Jossen V, Lindner M, Harder Y, Müller M, Eibl R, and Tallone T
- Abstract
Human adipose stem cells (hASCs) are promising candidates for cell-based therapies, but they need to be efficiently expanded in vitro as they cannot be harvested in sufficient quantities. Recently, dynamic bioreactor systems operated with microcarriers achieved considerable high cell densities. Thus, they are a viable alternative to static planar cultivation systems to obtain high numbers of clinical-grade hASCs. Nevertheless, the production of considerable biomass in a short time must not be achieved to the detriment of the cells' quality. To facilitate the scalable expansion of hASC, we have developed a new serum- and xeno-free medium ( UrSuppe ) and a biodegradable microcarrier ( BR44 ). In this study, we investigated whether the culture of hASCs in defined serum-free conditions on microcarriers (3D) or on planar (2D) cell culture vessels may influence the expression of some marker genes linked with the immature degree or the differentiated status of the cells. Furthermore, we investigated whether the biomaterials, which form our biodegradable MCs, may affect cell behavior and differentiation. The results confirmed that the quality and the undifferentiated status of the hASCs are very well preserved when they grow on BR44 MCs in defined serum-free conditions. Indeed, the ASCs showed a gene expression profile more compatible with an undifferentiated status than the same cells grown under standard planar conditions.
- Published
- 2021
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41. Chemically Defined Xeno- and Serum-Free Cell Culture Medium to Grow Human Adipose Stem Cells.
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Panella S, Muoio F, Jossen V, Harder Y, Eibl-Schindler R, and Tallone T
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- Adipose Tissue cytology, Humans, Stem Cells cytology, Adipose Tissue metabolism, Cell Culture Techniques methods, Stem Cells metabolism
- Abstract
Adipose tissue is an abundant source of stem cells. However, liposuction cannot yield cell quantities sufficient for direct applications in regenerative medicine. Therefore, the development of GMP-compliant ex vivo expansion protocols is required to ensure the production of a "cell drug" that is safe, reproducible, and cost-effective. Thus, we developed our own basal defined xeno- and serum-free cell culture medium ( UrSuppe ), specifically formulated to grow human adipose stem cells (hASCs). With this medium, we can directly culture the stromal vascular fraction (SVF) cells in defined cell culture conditions to obtain hASCs. Cells proliferate while remaining undifferentiated, as shown by Flow Cytometry (FACS), Quantitative Reverse Transcription PCR (RT-qPCR) assays, and their secretion products. Using the UrSuppe cell culture medium, maximum cell densities between 0.51 and 0.80 × 10
5 cells/cm2 (=2.55-4.00 × 105 cells/mL) were obtained. As the expansion of hASCs represents only the first step in a cell therapeutic protocol or further basic research studies, we formulated two chemically defined media to differentiate the expanded hASCs in white or beige/brown adipocytes. These new media could help translate research projects into the clinical application of hASCs and study ex vivo the biology in healthy and dysfunctional states of adipocytes and their precursors. Following the cell culture system developers' practice and obvious reasons related to the formulas' patentability, the defined media's composition will not be disclosed in this study.- Published
- 2021
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42. CT colonography followed by elective surgery in patients with acute diverticulitis: a radiological-pathological correlation study.
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Flor N, Pickhardt PJ, Maconi G, Panella S, Falleni M, Merlo V, and Di Leo G
- Subjects
- Acute Disease, Correlation of Data, Humans, Retrospective Studies, Colonography, Computed Tomographic, Diverticulitis, Diverticulitis, Colonic complications, Diverticulitis, Colonic diagnostic imaging, Diverticulitis, Colonic surgery
- Abstract
Purpose: To perform a radiologic-pathologic correlation analysis of sigmoid colon in patients undergoing pre-operative CT Colonography (CTC) after an episode of acute diverticulitis (AD)., Methods: Fifty-nine consecutive patients (31/28 M/F; 58 ± 13 years) underwent CTC 55 ± 18 days after AD, 8 ± 4 weeks before surgery. Thirty-seven patients (63%) underwent conventional abdominal CT at time of AD. An experienced blinded radiologist retrospectively analyzed all images: disease severity was graded according to the Ambrosetti classification on conventional CT and according to the diverticular disease severity score (DDSS) on CTC. A GI pathologist performed a dedicated analysis, evaluating the presence of acute and chronic inflammation, and fibrosis, using 0-3 point scale for each variable., Results: Of 59 patients, 41 (69%) had at least one previous AD episode; twenty-six patients (44%) had a complicated AD. DDSS was mild-moderate in 34/59 (58%), and severe in 25/59 (42%). All patients had chronic inflammation, while 90% had low-to-severe fibrosis. Patients with moderate/severe fibrosis were older than those with no/mild fibrosis (61 ± 13 versus 54 ± 13). We found a significant correlation between DDSS and chronic inflammation (p = 0.004), as well as DDSS and fibrosis (p = 0.005). Furthermore, fibrosis was correlated with complicated acute diverticulitis (p = 0.0.27), and with age (p = 0.067). At multivariate analysis, complicated diverticulitis was the best predictor of fibrosis (odds ratio 4.4). Patient age and DDSS were other independent predictors., Conclusion: DDSS-based assessment on preoperative CTC was a good predictor of chronic colonic inflammation and fibrosis. In addition, the presence of complicated diverticulitis on CT during the acute episode was most predictive of fibrosis.
- Published
- 2021
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43. An Approach towards a GMP Compliant In-Vitro Expansion of Human Adipose Stem Cells for Autologous Therapies.
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Jossen V, Muoio F, Panella S, Harder Y, Tallone T, and Eibl R
- Abstract
Human Adipose Tissue Stem Cells (hASCs) are a valuable source of cells for clinical applications (e.g., treatment of acute myocardial infarction and inflammatory diseases), especially in the field of regenerative medicine. However, for autologous (patient-specific) and allogeneic (off-the-shelf) hASC-based therapies, in-vitro expansion is necessary prior to the clinical application in order to achieve the required cell numbers. Safe, reproducible and economic in-vitro expansion of hASCs for autologous therapies is more problematic because the cell material changes for each treatment. Moreover, cell material is normally isolated from non-healthy or older patients, which further complicates successful in-vitro expansion. Hence, the goal of this study was to perform cell expansion studies with hASCs isolated from two different patients/donors (i.e., different ages and health statuses) under xeno- and serum-free conditions in static, planar (2D) and dynamically mixed (3D) cultivation systems. Our primary aim was I) to compare donor variability under in-vitro conditions and II) to develop and establish an unstructured, segregated growth model as a proof-of-concept study. Maximum cell densities of between 0.49 and 0.65 × 10
5 hASCs/cm2 were achieved for both donors in 2D and 3D cultivation systems. Cell growth under static and dynamically mixed conditions was comparable, which demonstrated that hydrodynamic stresses ( P/V = 0.63 W/m3 , τnt = 4.96 × 10-3 Pa) acting at Ns1u (49 rpm for 10 g/L) did not negatively affect cell growth, even under serum-free conditions. However, donor-dependent differences in the cell size were found, which resulted in significantly different maximum cell densities for each of the two donors. In both cases, stemness was well maintained under static 2D and dynamic 3D conditions, as long as the cells were not hyperconfluent. The optimal point for cell harvesting was identified as between cell densities of 0.41 and 0.56 × 105 hASCs/cm2 (end of exponential growth phase). The growth model delivered reliable predictions for cell growth, substrate consumption and metabolite production in both types of cultivation systems. Therefore, the model can be used as a basis for future investigations in order to develop a robust MC-based hASC production process for autologous therapies.- Published
- 2020
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44. The role of interventional radiology in the treatment of epiphora.
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Patella F, Panella S, Zannoni S, Jannone ML, Pesapane F, Angileri SA, Sbaraini S, Ierardi AM, Soldi S, Franceschelli G, and Carrafiello G
- Abstract
Epiphora is a relatively common ophthalmologic affection representing almost 5% of clinical consultations in ophthalmology and it consists in the complete or partial obstruction of nasolacrimal duct, leading to insufficient drainage of tears. The traditional treatment is represented by surgery namely, external dacryocystorhinostomy (DCR). Despite the high success rate DCR has many disadvantages and limitations since it requires general anesthesia, it may arise in a permanent facial scar and it is often affected by the reobstruction of the anastomotic tract by fibrotic scars and osteogenic activity. Fluoroscopically guided interventional procedures are a therapeutic alternative to surgery for lacrimal duct system obstructions that can consist either in balloon dacryocystoplasty or in nasolacrimal stent placement. In both cases, a pre-operative imaging characterization of the occlusion is needed for a correct treatment planning. In this review, we propose to highlight the role of interventional radiology in the treatment of epiphora and the role of computed tomography dacryocystography (CTD) in depiction and the pre-interventional planning., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2018
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45. Intravoxel Incoherent Motion (IVIM) Diffusion Weighted Imaging (DWI) in the Periferic Prostate Cancer Detection and Stratification.
- Author
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Pesapane F, Patella F, Fumarola EM, Panella S, Ierardi AM, Pompili GG, Franceschelli G, Angileri SA, Magenta Biasina A, and Carrafiello G
- Subjects
- Aged, Humans, Male, Middle Aged, Prospective Studies, Diffusion Magnetic Resonance Imaging methods, Prostatic Neoplasms diagnostic imaging
- Abstract
The aim of this study was to compare the Intravoxel Incoherent Motion (IVIM) parameters between healthy Peripheral Zone (PZ), Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PCa) and compare them to assess whether there was correlation with Gleason Score (GS) grading system. Thirty-one patients with suspect of PCa underwent 1.5T Multi-Parametric Magnetic Resonance Imaging (MP-MRI) with endorectal coil with a protocol including T2WI, DWI using 10 b values (0, 10, 20, 30, 50, 80, 100, 200, 400, 1000 s/mm
2 ) and DCE. Monoexponential and IVIM model fits were used to calculate both apparent diffusion coefficient (ADC) and the following IVIM parameters: molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*) and perfusion fraction (f). The ADC and D values were significantly lower in the PCa (0.70 ± 0.16 × 10-3 mm2 /s and 0.88 ± 0.31 × 10-3 mm2 /s) compared to those found in the PZ (1.22 ± 0.20 × 10-3 mm2 /s and 1.78 ± 0.34 × 10-3 mm2 /s) and in the BPH (1.53 ± 0.23 × 10-3 mm2 /s and 1.11 ± 0.28 × 10-3 mm2 /s). The D* parameter was significantly increased in the PCa (5.35 ± 5.12 × 10-3 mm2 /s) compare to the healthy PZ (3.02 ± 2.86 × 10-3 mm2 /s), instead there was not significantly difference in the PCa compare to the BPH (5.61 ± 6.77 × 10-3 mm2 /s). The f was statistically lower in the PCa (9.01 ± 5.20%) compared to PZ (10.57 ± 9.30%), but not significantly different between PCa and BPH (9.29 ± 7.29%). The specificity, sensitivity and accuracy of T2WI associated with DWI and IVIM were higher (100, 98 and 99%, respectively) than for T2WI/DWI and IVIM alone (89, 92 and 90%, respectively). Only for ADC was found a statistical difference between low- and intermediate-/high-grade tumors. Adding IVIM to the MP-MRI could increase the diagnostic performance to detect clinically relevant PCa. ADC values have been found to have a rule to discriminate PCa reliably from normal areas and differed significantly in low- and intermediate-/high-grade PCa. In contrast, IVIM parameters were unable to distinguish between the different GS.- Published
- 2017
- Full Text
- View/download PDF
46. The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma.
- Author
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Ierardi AM, Angileri SA, Patella F, Panella S, Lucchina N, Petre EN, Pinto A, Franceschelli G, Carrafiello G, Cornalba G, and Sofocleous CT
- Subjects
- Embolization, Therapeutic methods, Humans, Radiology, Interventional methods, Bile Duct Neoplasms radiotherapy, Cholangiocarcinoma radiotherapy
- Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. Complete surgical resection remains the only potentially curative option for patients with ICC. However, until now, early diagnosis with potential surgical intervention has been the exception rather than the rule with only 30% of patients qualifying for attempted surgical cure. Many patients are unresectable because of disease stage, anatomic conditions, medical comorbidities, and small future remnant liver. Interventional radiology procedures are available for these types of patients with intra-arterial therapies and/or ablative treatments both for curative and for palliative treatment. The goals of interventional therapy are to control local tumor growth, to relieve symptoms, and to improve and preserve quality of life. The choice of treatment depends largely on tumor extent and patient performance. No randomized studies exist to compare treatments. The present review describes the current evidence of the interventional treatments in the management of the ICC. Moreover, interventional procedures available to increase the future liver reserve before surgery were analyzed.
- Published
- 2017
- Full Text
- View/download PDF
47. The role of endovascular therapy in acute mesenteric ischemia.
- Author
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Ierardi AM, Tsetis D, Sbaraini S, Angileri SA, Galanakis N, Petrillo M, Patella F, Panella S, Balestra F, Lucchina N, and Carrafiello G
- Abstract
Background: Endovascular therapy, including aspiration thrombectomy and local thrombolytic therapy, often associated with angioplasty and stent placement, has been described in the literature. The purpose of this study was to review case series of patients with acute mesenteric ischemia treated with endovascular therapy and evaluate their outcomes., Methods: An online review using PubMed was carried out to identify all English articles about this topic in the time interval from 2005 to 2016., The Following Variables Were Extracted: number of patients, cause of occlusion, symptoms, arteries involved, number of sessions of treatment, technical success, clinical success, recurrence rate, complications, mortality rate, number of patients who underwent diagnostic laparoscopy or surgical resection of ischemic bowel., Results: Eighteen papers met the inclusion criteria and were included. Among the patients with arterial mesenteric ischemia treated with endovascular approach, the technical success rate was high (up to 100%) and data regarding clinical success are encouraging, even though they are few and heterogeneous. Technical success rate and clinical success of patients with acute venous mesenteric ischemia approached with endovascular treatment was 74-100% and 87.5-100% respectively., Conclusions: Current advances in endovascular therapies have made these treatments feasible for mesenteric ischemia., Competing Interests: Conflict of Interest: None
- Published
- 2017
- Full Text
- View/download PDF
48. Microwave ablation for thyroid nodules: a new string to the bow for percutaneous treatments?
- Author
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Morelli F, Sacrini A, Pompili G, Borelli A, Panella S, Masu A, De Pasquale L, Giacchero R, and Carrafiello G
- Abstract
Background: Thyroid nodules are a fairly common finding in general population and, even if most of them are benign, a treatment can be however necessary. In the last years, non surgical minimally invasive techniques have been developed to treat this pathology, starting from percutaneous ethanol injection (PEI), to laser ablation (LA), radiofrequency ablation (RFA) and, most recently, microwave ablation (MWA)., Methods: We reviewed all medical literature searching in pubmed.gov the terms "microwave" & "thyroid". We found three original studies concerning MWA treatment, for a total of 263 patients (mean age 51.0 years; range, 15-80 years; male to female ratio 2.55) and 522 nodules., Results: A total of 522 nodules (338 solid, 22 cystic, 162 mixed) in 263 patients were treated. Studies have shown a mean reduction in volume of thyroid nodules ranging from 45.9% to 65%. No study reported a significant and definitive change in laboratory parameters, except for one case (Heck et al. ). No studies have reported major complications after procedure., Conclusions: MWA is a new, promising technique among the minimally invasive treatments of thyroid nodules. Actually, the larger diameter of MW antenna seems to be the major limiting factor in the use of this technique. More studies are necessary to evaluate feasibility, safety and efficacy of the procedure., Competing Interests: The authors have no conflicts of interest to declare.
- Published
- 2016
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49. MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation.
- Author
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Panella S, Marcocci ME, Celestino I, Valente S, Zwergel C, Li Puma DD, Nencioni L, Mai A, Palamara AT, and Simonetti G
- Abstract
Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells., Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication., Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy.
- Published
- 2016
- Full Text
- View/download PDF
50. Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress.
- Author
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Checconi P, Salzano S, Bowler L, Mullen L, Mengozzi M, Hanschmann EM, Lillig CH, Sgarbanti R, Panella S, Nencioni L, Palamara AT, and Ghezzi P
- Subjects
- Animals, Antioxidants pharmacology, Blotting, Western, Cell Line, Dexamethasone pharmacology, Down-Regulation drug effects, Humans, Inflammation complications, Inflammation pathology, Influenza, Human complications, Influenza, Human pathology, Lipopolysaccharides pharmacology, Mice, Oxidation-Reduction drug effects, Peroxiredoxins metabolism, Profilins metabolism, RAW 264.7 Cells, Sulfhydryl Compounds pharmacology, Thioredoxins metabolism, Vimentin metabolism, Glutathione metabolism, Inflammation metabolism, Influenza, Human metabolism, Oxidative Stress drug effects, Proteins metabolism, Proteomics
- Abstract
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions.
- Published
- 2015
- Full Text
- View/download PDF
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