Locally advanced leiomyosarcoma of the spleen. A case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Leiomyosarcomas are rare tumours, predominantly localized in the stomach, small intestine and retroperitoneum. Only one case of primary leiomyosarcoma of the spleen is described in human beings in literature.</p> <p>Case presentation</p> <p>We report a case of locally advanced primary leiomyosarcoma of the spleen in a 54 year-old woman, diagnosed only after splenectomy, performed with the suspicion of splenic haematoma.</p> <p>Conclusion</p> <p>Due to the lack of cases, no specific chemotherapy regimen has been tested to provide a longer survival.</p

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis &lt; 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11&nbsp;years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

The Thin Light Trigger for the UA9 experiment

We realized a Thin Light Trigger (TLT) device based on thin plastic scintillator layer and Multi Pixel-Photon Counters (MPPC) readout, controlled via Ethernet, for the H8 telescope of the UA9 experiment. The UA9 experimental equipment was installed in the CERN-SPS in the 2009. The UA9 goals are to demonstrate the feasibility of a collider collimation scheme with a crystal as the primary collimator Measurements of suitable crystals are being carried out in the SPS ring as well as in a fixed target experiment at the H8 line in the CERN North experimental area. The aim of the TLT is to supply an upstream trigger for the H8 beam line telescope in order to select incoming protons. It has to be thin enough to minimize multiple scattering, which increases angular divergence, and hadronic interaction probability but it has to be sufficiently thick to yield enough light. The detector is made up of a 9×9 mm2 scintillator window, made up of 2 layers of scintillating fibers, coupled with 4 Multi Pixel-Photon (MPPC). Hamamatsu S10362-33 MPPC are driven by an embedded board supplying bias voltage and analog readout channels made up of low-noise, high gain, fast recovery voltage amplifiers. ARDUINO based control electronics allows temperature monitoring and gain calibration of MPPC by Ethernet with a simple html-based user interface. TLT system was tested in June 2013 at The DAFNE Beam-Test Facility (LNF - Frascati (RM)) by fine-adjustable-multiplicity 500MeV electron's beam. © 2013 IEEE

Electromagnetically actuated surface micromachined free standing torsion beam micromirror made by electroplated nickel

In this paper we report extremely simple 2-mask exposure fabrication process using photoresist as sacrificial layer to fabricate electromagnetically actuated torsion beam micromirror. The important feature of this reported include that the torsion beam and micromirror body are made of low stress electroplated nickel, and the torsion beam micromirror is testing on a free standing structural frame also made of electroplated copper. This device structure has resulted in a simplified fabrication process. The electroplated, low stress nickel piece having a dimension 1200 x 1400 x 4 mum(3) constitutes the mirror body and is used as reflective surface as well for magnetic interaction with magnetic field. Electromagnetic actuation in mirror is realized by control of current through a set of 500 turns copper coils on 7 cm long iron pole to which free standing mirror fixture was integrated. This structure is capable to have bi-directional actuation and a maximum deflection >24degrees has been obtained in static mode for the investigated electromagnet's coil current. The electromagnetically induced deflection of our torsion mirror were modeled and shown to agree with experimental measurements

A INTRACORONARY CYTOPROTECTIVE GENE THERAPY IN CANINE PATIENTS WITH DILATED CARDIOMYOPATHY

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of cardiac failure. Cytoprotective gene therapy with the Vascular Endothelial Growth Factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs [1,2]. The aim of this work was to test the tolerability and feasibility of intracoronary inoculation under fluoroscopic guidance of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessment at 7 days post-procedure in all dogs showed stable clinical conditions that could be superimposed to those pre-procedure. The results of this work indicate that intracoronary gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this procedure on disease progr

Stress lavoro-correlato e mobbing: diagnosi multidisciplinare e casistica clinica

Il D.lgs. 81/2008, all’art. 28, sancisce che la valutazione dei rischi (indispensabile premessa a eventuali interventi preventivi) deve comprendere «anche quelli collegati allo stress lavoro-correlato». Nel contempo, l’attenzione di medici e non-medici è stata richiamata da un fenomeno emergente: il “mobbing”, termine con il quale si fa riferimento a molestie psicologiche, quasi sempre intenzionali, ripetute e prolungate (almeno 6 mesi) nei confronti di un lavoratore, dovute ad azioni ostili condotte solitamente dal superiore o da un piccolo gruppo di colleghi, esercitate attraverso comportamenti aggressivi, persecutori e lesivi della dignità personale e professionale, in grado di provocare danni alla salute psicofisica e ingenti perdite economiche in termini di produttività e assenze dal lavoro. Presso il nostro Istituto è attivo da molti anni un percorso diagnostico multidisciplinare per i disturbi riconducibili a stress lavoro-correlato e, in particolare, a mobbing. Obiettivo dello studio:valutare frequenza, differenze di genere e qualifica lavorativa dei disturbi psichiatrici correlabili a stress lavoro-correlato nella pratica clinica. Dal 2003 fino al 2016 sono stati valutati 834 pazienti (483 donne e 351 uomini; età media ± DS: 45,1 ± 9,1 anni) che riferivano problemi di salute da loro attributi a vessazioni subite in ambito lavorativo o ad altre forme di stress occupazionale. Essi sono stati indagati con strumenti di psicodiagnosi (MMPI-2, SCID ed intervista strutturata per DSM), anamnesi integrata e visite di specialisti psichiatri e medici del lavoro. Degli 834 pazienti che compongono la casistica, 9 (1,1%) non hanno terminato il percorso diagnostico (drop out), 276 pazienti (33,1%) non risultavano affetti da patologie psichiatriche, 124 (14,8%) presentavano disturbi psichiatrici (depressione, ansia, psicosi) non correlabili al lavoro, 350 (42%) ansia correlata al lavoro. In 72 casi (8,6%) si è posta diagnosi di disturbo dell’adattamento (DA) e in 3 (0.4%) di disturbo post-traumatico da stress (DPTS), correlabili a mobbing o costrittività organizzative, per un totale di 75 segnalazioni di malattia professionale alle Autorità competenti. Di queste, il 61,3% riguardava donne, il 38,7% uomini; il 13,3% aveva qualifica di dirigente, il 14,7% di quadro, il 30,7% di impiegato, il 34,7% di operaio, il 6.6% altra qualifica. Al termine del percorso diagnostico, una sindrome psichiatrica lavoro-correlata (AD o PTSD) è stata identificata in meno del 10% dei casi. Questo conferma la necessità di un rigoroso e prudente percorso interdisciplinare, volto a selezionare i casi per i quali avviare procedure medico-legali. Le donne e i lavoratori del terziario (white collars) sono più frequentemente coinvolti. Lo studio richiama inoltre la necessità di adeguate misure preventive

INTRACORONARY CYTOPROTECTIVE GENE THERAPY IN CANINE PATIENTS WITH DILATED CARDIOMYOPATHY

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of cardiac failure. Cytoprotective gene therapy with the Vascular Endothelial Growth Factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs [1,2]. The aim of this work was to test the tolerability and feasibility of intracoronary inoculation under fluoroscopic guidance of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessment at 7 days post-procedure in all dogs showed stable clinical conditions that could be superimposed to those pre-procedure. The results of this work indicate that intracoronary gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this procedure on disease progression. [1] Woitek et al. Intracoronary Cytoprotective Gene Therapy, Journal of the American College of Cardiology; 66(2):139-153, 2015 [2] Pepe et al. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy. Circulation Research;106(12):1893-1903, 201

CanB, a Druggable Cellular Target in Mycobacterium tuberculosis

Treatment against tuberculosis can lead to the selection of drug-resistant Mycobacterium tuberculosis strains. To tackle this serious threat, new targets from M. tuberculosis are needed to develop novel effective drugs. In this work, we aimed to provide a possible workflow to validate new targets and inhibitors by combining genetic, in silico, and enzymological approaches. CanB is one of the three M. tuberculosis β-carbonic anhydrases that catalyze the reversible reaction of CO2 hydration to form HCO3– and H+. To this end, we precisely demonstrated that CanB is essential for the survival of the pathogen in vitro by constructing conditional mutants. In addition, to search for CanB inhibitors, conditional canB mutants were also constructed using the Pip-ON system. By molecular docking and minimum inhibitory concentration assays, we selected three molecules that inhibit the growth in vitro of M. tuberculosis wild-type strain and canB conditional mutants, thus implementing a target-to-drug approach. The lead compound also showed a bactericidal activity by the time-killing assay. We further studied the interactions of these molecules with CanB using enzymatic assays and differential scanning fluorimetry thermal shift analysis. In conclusion, the compounds identified by the in silico screening proved to have a high affinity as CanB ligands endowed with antitubercular activity