Approccio demografico allo studio della popolazione mediterranea di Balenottera comune (Balaenoptera physalus L 1758)

Il lavoro di ricerca di questa tesi ha come scopo l’analisi demografica e l’applicazione di modelli adeguati alla popolazione mediterranea di balenottera comune. Il modello demografico si baserà, in particolare, sui dati raccolti dall’Istituto Tethys dal 1990 al 2007 nel Santuario Pelagos ed esaminati tramite foto-identificazione. Nel corso di questi 18 anni sono stati foto-identificati 431 individui diversi che rappresentano poco meno della metà degli individui stimati nel 1992 per la popolazione di balenottera comune del Santuario dei cetacei (circa 900 individui; Forcada et al., 1995). I dati del campione, stratificati per classi di taglia e di età, vengono utilizzati, insieme agli studi di Aguilar e Lockyer (1987) sulla popolazione atlantico-spagnola, alla letteratura riguardante le collisioni (Panigada et al., 2006) e gli spiaggiamenti (database CIBRA e database europei), al fine di ricostruire la life-table della popolazione. Su queste basi sarà possibile procedere alla messa a punto di una prima modellizzazione della popolazione mediterranea. Questa tesi rappresenta l’inizio di un progetto di collaborazione a lungo termine tra il gruppo di lavoro di Zoologia del Dipartimento di Biologia, il settore di Demografia del Dipartimento di Economia dell’Università di Pisa e l’Istituto Tethys, volto allo studio demografico dei cetacei mediterranei

The High Mobility Group (Hmg) Boxes of the Nuclear Protein Hmg1 Induce Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells

HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a Gi/o protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage

Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Rationale: KRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies. The focus of this review will be to provide an overview of the network related to the intricate molecular KRAS pathways, stressing on preclinical and clinical studies that investigate the predictive value of KRAS mutations in NSCLC patients. Materials and Methods: A bibliographic search of the Medline database was conducted for articles published in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer, KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance

Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis

We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed by dipyridamole, a phosphodiesterase inhibitor. h-prune physically interacts with nm23-H1, a metastasis suppressor gene. The h-prune PDE activity, suppressed by dipyridamole and enhanced by the interaction with nm23-H1, stimulates cellular motility and metastasis processes. Out of 59 metastatic breast cancer cases analyzed, 22 (37%) were found to overexpress h-prune, evidence that this novel enzymatic activity is involved in promoting cancer metastasis

Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue

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Twenty questions from the surgeon to the radiologist to better plan an open partial horizontal laryngectomy

Open partial horizontal laryngectomies (OPHLs) represent a valuable therapeutic option for tumors of the intermediate T-category and, in selected cases, for locally advanced tumors with low-volume extra-laryngeal extension. The eligibility of patients treated with this type of surgery has increased with the introduction of the modular approach to OPHL planning. This strategy follows the introduction of the classification proposed by the European Laryngological Society, based on the extent of horizontal resection. Optimization of the selection is the result of a meticulous work-up process involving close cooperation between experienced surgeons and radiologists, followed by final quality control by pathologists. Computed tomography and magnetic resonance imaging are study methods whose pearls and pitfalls are well known, especially when performed at a high level of expertise. In this paper, based on the experience of two high-volume centers, a checklist of 20 questions addressed by the surgeon to the radiologist before planning an OPHL was proposed. Considerations regarding case selection are reported for each of the questioned parameters. A very simple question-and-answer process is easy to understand and mainly addressed by less experienced colleagues who wish to increase their knowledge and skills in performing this type of surgery

VEGAS: A VST Early-type GAlaxy Survey. II. Photometric study of giant ellipticals and their stellar halos

Observations of diffuse starlight in the outskirts of galaxies are thought to be a fundamental source of constraints on the cosmological context of galaxy assembly in the $\Lambda$CDM model. Such observations are not trivial because of the extreme faintness of such regions. In this work, we investigate the photometric properties of six massive early type galaxies (ETGs) in the VEGAS sample (NGC 1399, NGC 3923, NGC 4365, NGC 4472, NGC 5044, and NGC 5846) out to extremely low surface brightness levels, with the goal of characterizing the global structure of their light profiles for comparison to state-of-the-art galaxy formation models. We carry out deep and detailed photometric mapping of our ETG sample taking advantage of deep imaging with VST/OmegaCAM in the g and i bands. By fitting the light profiles, and comparing the results to simulations of elliptical galaxy assembly, we identify signatures of a transition between "relaxed" and "unrelaxed" accreted components and can constrain the balance between in situ and accreted stars. The very good agreement of our results with predictions from theoretical simulations demonstrates that the full VEGAS sample of $\sim 100$ ETGs will allow us to use the distribution of diffuse light as a robust statistical probe of the hierarchical assembly of massive galaxies.Comment: Accepted for publication in Astronomy & Astrophysic

Influence of safety warnings on the prescribing attitude of JAK 2inhibitors for rheumatoid arthritis in Italy

The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA) and 74 filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US 75 Food & Administration (FDA) raised concerns on the safety of TOFA after its approval. This 76 prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA 77 use then extended in a third warning to all Jaki in patients at high risk of developing serious adverse 78 events (SAE). These included thrombosis, major adverse cardiac events (MACE) and cancer. Thepurpose of this work was to analyze how the first two safety warnings from EMA affected the pre- 80 scribing of Jaki by rheumatologists in Italy. All patients with rheumatoid arthritis who had been 81 prescribed JAKi for the first time in a 36-month period from July 1, 2019, to June 30, 2022 were con- 82 sidered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology 83 centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi 84 prescription had occurred before the EMA's first safety alert (July 1-October 31, 2019, Group 1), 85 between the first and second alerts (November 1, 2019-February 29, 2020, Group 2), or between the 86 second and third alerts (March 1, 2021-June 30, 2021, Group 3). Percentage and absolute changes in 87 patients prescribed the individual JAKi were analyzed. Differences among the three Groups of pa- 88 tients in demographic and clinical characteristics were also assessed. A total of 864 patients were 89 prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 90 in Group 2 and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients 91 prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, 92 there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In 93 the first Group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed 94 by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second Group, the most prescribed JAKi was BARI 95 (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third Group, BARI was still 96 the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%) 97 and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between 98 Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). Patients who were prescribed 99 BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p 100 ˂ 0.01). In contrast, patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). 101 These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi 102 prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers 103 as favorable in terms of risk/benefit ratio and their use gradually increased at the expense of the 104 other molecules

Off-pump Y-graft coronary artery bypass in a patient with situs inversus totalis

Situs inversus is the mirror image of situs solitus. Situs inversus with dextrocardia is termed 'situs inversus totalis'. Since situs inversus totalis is a rare condition, there are a only a few reports about off-pump coronary artery bypass (OPCAB) in these patients. A 67-year-old man with a diagnosis of situs inversus totalis and three-vessel disease, underwent an elective surgical revascularization. The operation consisted of an OPCAB using a total arterial composite Y-graft. The right internal mammary artery (RIMA) and the left radial artery (RA) were harvested as pedicles and they were anastomized as Y-grafts. Three distal anastomoses were performed: the RIMA to the anterior descending artery and the RA sequentially to the obtuse marginal branch and the posterior descending artery. The peculiarity of OPCAB no-touch with a composite graft in a patient with situs inversus totalis consisted in the mirroring of the whole surgical set-up and of the surgical strategy. The surgery as well as the postoperative period were uneventful. This case report shows the feasibility of OPCAB 'no-touch' with composite arterial grafting in a patient with situs inversus totalis. (C) 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved