Congenital factor XI and factor VII deficiencies assure an apparent opposite protection against arterial or venous thrombosis: An intriguing observation.

To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency.Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods.Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively.Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications

Rethinking the Urban Green Spaces by the Lens of GIScience: the Experience of the Project Living Urban Parks

In Italy, soil sealing is a major threats in terms of soil degradation and the loss of urban ecosystem services. The increase in new artificial surfaces or settlement areas at the expense of green and rural areas is intensifying the effects of climate change, in particular extreme weather events, such as the increase in intense precipitation and heatwaves. In this context, the Municipality of Padua is a paradigmatic case study. According to the Italian Institute for Environmental Protection and Research (2022), almost 50% of the municipal territory is completely sealed, making it the Italian city with the fifth highest values of soil sealing. To contrast the phenomenon, the EU soil strategy for 2030 suggested, among other strategies, the implementation of Nature-Based Solutions, strengthened with the participation and involvement of non-expert actors to be more efficient and effective. This study was developed within the Living Urban Parks (LUP) project (Key Action 3, Erasmus + Programme EU) during two years of research and participatory activities (2020–2022) within the Municipality of Padua. It aims to involve youths aged 18–30 in a public process to reconceive of the urban green spaces of the city and to develop ideas and proposals for more sustainable urban planning, promoting participatory methodologies by using geographical tools (digital and traditional cartography). More than 400 participants were directly involved in the project. All the ideas and proposals mapped during the seminars and workshops have been uploaded to the geoplatform Geocitizen. This geotool is usable on smartphones and tablets and, thanks to its interactive features and a geodatabase, allows the collection of georeferenced ideas, good practices and urban issues regarding green areas and parks. By the end of the project, 118 points had been collected on Geocitizen. Beyond the Geocitizen platform, the participants had the opportunity to test other geotools, such as Geopaparazzi and Google Earth Pro. In addition, the participants were able to present their ideas collected on the platform and directly interact with the local decision-makers who were involved to discuss and promote effective and efficient actions for the enhancement of the green areas and urban parks of the city. The use of different geographic technologies combined with participatory mapping approaches allowed an increase in the knowledge of the urban territory by making people more aware of the issue of soil sealing and urban regeneration opportunities. Finally, LUP allowed to reconception and design of green spaces to promote the restoration of degraded and abandoned areas and to propose the implementation of Nature-Based Solutions

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

CONGENITAL ERYTHROCYTOSIS ARE RARE DISORDERS WITH MANY GENES INVOLVED. FUNCTIONAL EVALUATION OF NOVEL PHD2 AND EPOR MUTATIONS.

Congenital Erythrocytosis (CE) are rare and heterogeneous clinical entities. They are caused by genetic deregulation of the erythroid production resulting in increased production of red blood cells (RBCs). Primary Congenital Familial Polycythemia (PCFP) is due to erythropoietin receptor (EPOR) mutations and is associated with reduced levels of serum erythropoietin (EPOs). Secondary CE are characterized by high EPOs levels, may be due to mutations of the oxygen-sensing pathway (OSP) genes: von Hippel-Lindau (VHL), hypoxia-inducible factor 2 alpha (HIF2A/EPAS1) and prolyl hydroxylase 2 (EGLN1/PHD2). Within 106 patients followed in our centre with sporadic not myeloproliferative erythrocytosis we found 9 mutations (8,5%) in the involved genes. Here we report the functional studies of 1 novel PHD2 (c.1045G>A) and of 2 EPOR gene missense mutations (c.1013G>A and c.1022C>T). To evaluate the HIF transcriptional activity of PHD2 mutation, an in cellulo reporter assay has been performed, while the hydroxylation capacity of PHD2 variants has been tested with an in vitro Hydroxylation test. PHD2 variant does not show a clear loss-of-function of the PHD2 proteins. More sensitive tests could be developed and other PHD2 partners may be tested in this patient. The activation of EPOR mutated signaling was evaluated with a kinetic assay using transfected K562 cell lines. The EPOR signaling cascade results more active in mutated cells than in the WT cells when stimulated with EPO as shown by higher phosphorylation of STAT5 and ERK. Both mutations impair the C-terminal negative regulatory domain and determine gain-of-function in the EPOR signalling cascade. These are the first missense mutations of EPOR with a functional demonstrated activity that affect the EPOR signaling cascade. Other candidate genes need to be investigated to completely understand the ethiology of high hematocrit (HCT) level both in congenital and sporadic erythrocytosisLe Eritrocitosi Congenite (CE) sono entità cliniche rare ed eterogenee. Esse sono causate dalla deregolazione genetica della produzione eritroide con conseguente incremento della produzione delle cellule rosse del sangue (RBCs). La Policitemia Congenita Primaria Familiare (PCFP) è dovuta a mutazioni del recettore dell’eritropoietina (EPOR) ed è associata a bassi livelli di eritropoietina sierica (EPOs). Le CE secondarie, invece, sono caratterizzate da elevati valori di EPOs dovuti ad alterazioni dei geni dell’ Oxygen Sensing Pathway (OSP): von Hippel- Lindau (VHL), hypoxia-inducible factor 2 alpha (HIF2A/EPAS1) e prolyl hydroxylase 2 (EGLN1/PHD2). Nel nostro centro sono stati seguiti 106 pazienti con eritrocitosi sporadica non mieloproliferativa nei quali abbiamo trovato 9 mutazioni (8,5%) nei geni candidati. Al fine di valutare l’attività trascrizionale di HIF in presenza di PHD2 mutato è stato messo a punto un reporter assay in cellulo, mentre l’attività di idrossilazione di PHD2 è stata testata con un hydroxylation test in vitro. Non è stata riscontrata una chiara loss-of-function per la variante di PHD2 nonostante il link mutazione-malattia. Pertanto si necessita lo sviluppo di test più sensibili oltre allo studio di altri geni partner. La cascata del segnale di EPOR mutato è stata studiata effettuando una cinetica di stimolazione su cellule K562 trasfettate. In seguito a stimolazione con EPO il signaling di EPOR è risultato più attivo in condizioni mutate rispetto al wild type rilevando alti livelli di fosforilazione di STAT5 e ERK. Entrambe le mutazioni compromettono il dominio regolatore negativo C-terminale di EPOR causando una gain-of-function del recettore. Queste sono le prime mutazioni missenso in cui in cui è stata rilevata un’iperattivazione dei componenti della cascata del segnale di EPOR. Altri geni candidati devono essere investigati per comprendere completamente l’eziologia degli alti valori di ematocrito (HTC) sia nei casi di eritrocisi sporadiche sia in quelle congenite

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment

Abstract Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard “one size fits all” treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine. The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach. Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a “tailored” therapeutic approach based also on engineered CAR-T cells

Insights on Metabolic Reprogramming and Its Therapeutic Potential in Acute Leukemia

Acute leukemias, classified as acute myeloid leukemia and acute lymphoblastic leukemia, represent the most prevalent hematologic tumors in adolescent and young adults. In recent years, new challenges have emerged in order to improve the clinical effectiveness of therapies already in use and reduce their side effects. In particular, in this scenario, metabolic reprogramming plays a key role in tumorigenesis and prognosis, and it contributes to the treatment outcome of acute leukemia. This review summarizes the latest findings regarding the most relevant metabolic pathways contributing to the continuous growth, redox homeostasis, and drug resistance of leukemia cells. We describe the main metabolic deregulations in acute leukemia and evidence vulnerabilities that could be exploited for targeted therapy

Venous thrombosis in von Willebrand disease as observed in one centre and as reported in the literature.

The aim of this article was to investigate the prevalence of venous thrombosis in patients with von Willebrand disease. Personal records on 486 patients were reevaluated together with a time unlimited PubMed search. The venous thrombotic event had to be proven by objective means. Only cases of congenital von Willebrand disease were taken into consideration and all types of the diseases were included. No case of venous thrombosis was reported in our cohort of patients. On the contrary, 33 patients with proven venous thrombosis were gathered from the literature (17 cases of deep venous thrombosis with or without pulmonary embolism; isolated pulmonary embolism was seen in seven instances, superficial veins or portal system thrombosis was present in the remaining cases). Associated risk factors, mainly replacement therapy, were present in 26 cases. Therapeutic approach was usually based on heparin and Coumadin. Overall results were fair or good, as no fatalities occurred

De Marchi, Massimo

Con il rapido sviluppo delle tecnologie digitali per la raccolta, gestione diffusione di dati spaziali, la ricerca geografica ha beneficiato in anni recenti di numerosi contributi basati sulla partecipazione o collaborazione di cittadini, singolarmente o in gruppo, facilitata da tecnologie dell’informazione geografica, geotool, geoapp. Processi di questo genere possono essere catalogati sotto diverse terminologie: Citizen Science, Volunteered Geographic Information (VGI), Participatory Mapping, Public Participation Geographic Information Systems (PPGIS) e altre ancora. Uno dei campi di applicazione più diffusi delle ricerche basate sull’interazione tra ricercatori e cittadini è la realtà urbana, in special modo le azioni di mappatura di tematismi rilevanti dal punto di vista sociale o ambientale. Nel Laboratorio GIScience e Drones for Good attivo presso il Dipartimento di Ingegneria Civile Edile e Ambientale dell’Università di Padova, e con la collaborazione di altri dipartimenti, il gruppo di ricerca collegato al Master di II livello in GIScience e Sistemi a Pilotaggio Remoto per la gestione integrata del territorio e delle risorse naturali sviluppa da alcuni anni una linea di ricerca fondata su metodologie di mappatura partecipata a supporto di analisi sulla sostenibilità urbana. In questo contributo vengono illustrati tre dei progetti afferenti a tale linea di ricerca: “Il Valore del Suolo”, per mappare la permeabilità delle superfici in un quartiere campione di Padova; “Piste riCiclabili”, per individuare le criticità dei percorsi ciclabili padovani; “MUES – Mapping Urban Empty Spaces”, per la mappatura di spazi abbandonati nel comune di Padova. Per ogni progetto si descrivono obiettivi, metodologie, tecnologie dell’informazione geografica utilizzate, attori coinvolti e risultati ottenuti, allo scopo di trovare connessioni tra questi elementi e ragionare su pregi e limiti di tali operazioni.The rapid development of digital technologies to collect, manage and spread spatial data has led the geospatial research field to be involved in a great number of projects based on participation by citizens, both individually and in groups, facilitated by geographic information technologies, geotools, geoapps. Such processes may be classified under different terms and definitions: Citizen Science, Volunteered Geographic Information (VGI), Participatory Mapping, Public Participation Geographic Information Systems (PPGIS) and more. One of the most common fields of application for interaction-based geographical researches is the urban context, especially mapping features and themes which are relevant from a social or environmental point of view. Within the GIScience e Drones for Good Lab, part of the Department of Civil, Environmental and Architectural Engineering of University of Padova, and with the collaboration of other departments, the group linked to the post-graduate Master in GIScience and UAV has been leading for several years a line of research based on participatory mapping methodologies in support of urban sustainability analysis. Here, three of the performed projects are presented: “Il Valore del Suolo”, to map perviousness of surfaces in a sample neighbourhood in Padova; “Piste Riciclabili”, to detect critical issues in Padova cycle paths; “MUES – Mapping Urban Empty Spaces”, to map abandoned sites in Padova. For each of these projects, objectives, methodologies, involved geographic information technologies and actors, results are described, with the aim to find connections between such elements and think about pros and cons of these kinds of processes