A Perspective on Recent Advances in Phosphorene Functionalization and its Application in Devices

Phosphorene, the 2D material derived from black phosphorus, has recently attracted a lot of interest for its properties, suitable for applications in material science. In particular, the physical features and the prominent chemical reactivity on its surface render this nanolayered substrate particularly promising for electrical and optoelectronic applications. In addition, being a new potential ligand for metals, it opens the way for a new role of the inorganic chemistry in the 2D world, with special reference to the field of catalysis. The aim of this review is to summarize the state of the art in this subject and to present our most recent results in preparation, functionalization and use of phosphorene and its decorated derivatives. In particular, we discuss several key points, which are currently under investigation: the synthesis, the characterization by theoretical calculations, the high pressure behaviour of black phosphorus, as well as decoration with nanoparticles and encapsulation in polymers. Finally, device fabrication and electrical transport measurements are overviewed on the basis of recent literature and new results collected in our laboratories

Assistenza domiciliare integrata: caratteristiche, problematiche e prospettive

L'assistenza domiciliare integrata (ADI) in Italia fin dalla sua nascita negli anni '80 ha sempre sofferto di svariati problemi, dal modello di valutazione del paziente al sistema di pagamento della prestazione, dalla qualità del servizio dipendente dal distretto alla necessità di una presenza strutturata di care giver familiare. Nell'articolo 10 direttori sanitari di diverse regioni italiane portano alla luce le difficoltà principali del servizio ADI nel nostro Paese, offrendo al contempo spunti al miglioramento dello stesso. È importante, infatti, che il servizio ADI migliori le proprie performance in questo momento storico che richiede ai SSR risposte dal territorio al fine di mantenere il più possibile al domicilio gli assistiti con qualità elevate dell'assistenza e della cura.The Italian Integrated home healthcare (ADI) has suffered, since its 1980's institution, various problems, starting from the patient's evaluation to the provider's payment system, and again from the service's quality – which depends on the local health District organization – to the family care giver, when present within the family. This paper reports the discussion held by 10 chief medical officers coming from different Italian regions, where the main difficulties of the ADI service are evaluated, and possible improvements suggested. ADI must at this point improve its performance, providing the answers the Regional Healthcare System (SSR) needs in order to offer the highest quality and most appropriate clinical assistance and care the patient needs at home

Risk-Reducing Salpingo-Oophorectomy (RRSO) Combined with Simultaneous Mastectomy in Women with BRCA 1-2 Mutation Carriers: The Surgical Technique, the Feasibility and Patients' Satisfaction of Multiple Surgeries

: The main goal of our study was to evaluate the surgical technique, the feasibility and patient's satisfaction of multiple surgeries: Risk-reducing salpingo-oophorectomy (RRSO) combined with mastectomy in patients with BRCA 1-2 mutation carriers. We conducted a retrospective analysis of patients with BRCA 1-2 variants who underwent RRSO combined with risk-reducing bilateral mastectomy (RRBM) or surgeries for breast cancer from January-2015 to December-2021. We collected data about surgeries, complications, and patients' satisfaction using a questionnaire submitted 30 days after surgery. We included 54 patients. Forty-eight patients underwent RRSO, and six patients underwent RRSO + Total laparoscopic hysterectomy (LTH). The minor postoperative complications within 30 days were four: one breast seromas aspiration (1.9%), one infectious reconstructive complication treated with antibiotics therapy (1.9%), one Red-Breast-Syndrome (1.9%) and one trocar abdominal hematoma (1.9%) associated with RRSO. The major postoperative complications within 30 days were five: two evacuations of a breast hematoma (3.7%) and three infectious reconstructive complications treated with removal expander/implant (5.6%). No postoperative complications after 30 days were observed. According to the satisfaction questionnaire, more than 90% of patients were satisfied and would have combined surgery again. In conclusion, the multiple surgeries seem feasible and safety with a single anesthesia, a single surgical time, a single postoperative recovery, and a high patients' satisfactions without increasing morbidity

In vitro and ex vivo rescue of a nonsense mutation responsible for severe coagulation factor V deficiency

Background: Coagulation factor V (FV) deficiency is a rare bleeding disorder that is usually managed with fresh-frozen plasma. Patients with nonsense mutations may respond to treatment with readthrough agents. Objectives: To investigate whether the F5 p.Arg1161Ter mutation, causing severe FV deficiency in several patients, would be amenable to readthrough therapy. Methods: F5 mRNA and protein expression were evaluated in a F5 p.Arg1161Ter-homozygous patient. Five readthrough agents with different mechanisms of action, i.e. G418, ELX-02, PTC-124, 2,6-diaminopurine (2,6-DAP), and Amlexanox, were tested in in vitro and ex vivo models of the mutation. Results: The F5 p.Arg1161Ter-homozygous patient showed residual F5 mRNA and functional platelet FV, indicating detectable levels of natural readthrough. COS-1 cells transfected with the FV-Arg1161Ter cDNA expressed 0.7% FV activity compared to wild-type. Treatment with 0-500 μM G418, ELX-02, and 2,6-DAP dose-dependently increased FV activity up to 7.0-fold, 3.1-fold, and 10.8-fold, respectively, whereas PTC-124 and Amlexanox (alone or in combination) were ineffective. These findings were confirmed by thrombin generation assays in FV-depleted plasma reconstituted with conditioned media of treated cells. All compounds except ELX-02 showed some degree of cytotoxicity. Ex vivo differentiated megakaryocytes of the F5 p.Arg1161Ter-homozygous patient, which were negative at FV immunostaining, turned positive after treatment with all 5 readthrough agents. Notably, they were also able to internalize mutant FV rescued with G418 or 2,6-DAP, which would be required to maintain the crucial platelet FV pool in vivo. Conclusion: These findings provide in vitro and ex vivo proof-of-principle for readthrough-mediated rescue of the F5 p.Arg1161Ter mutation

Whole blood thrombin generation shows a significant hypo-coagulable state in patients with decompensated cirrhosis

BACKGROUND: Patients with cirrhosis have a normal to increased thrombin generation (TG) capacity in platelet-poor plasma (PPP). By reflecting the contribution of all circulating blood cells, whole blood (WB) TG may allow a more physiological assessment of coagulation. OBJECTIVES: We compared WB-TG vs PPP-TG in patients with cirrhosis. METHODS: Assessment of coagulation included routine tests, factor VIII, natural anticoagulants, PPP-TG, and WB-TG. TG assays were performed with and without thrombomodulin. Twenty-five healthy subjects were included as controls. RESULTS: We included 108 patients (Child-Pugh A/B/C, 44/24/40). Compared with controls, patients had significantly lower platelet count, longer international normalized ratio, higher FVIII, and lower levels of protein C/S and antithrombin. Regarding thrombomodulin-modified TG assays, in compensated cirrhosis, both PPP-TG and WB-TG indicated an increased TG capacity, as reflected by an endogenous thrombin potential (ETP) significantly higher than controls. In contrast, in decompensated cirrhosis, PPP-TG indicated a hypercoagulable state with increased ETP, higher peak height, and shorter time-to-peak than controls, whereas WB-TG revealed a progressive impairment of TG kinetics and total capacity, ultimately resulting in a profound hypocoagulable state in patients with Child-Pugh C cirrhosis (ie, significant prolongation of lag time and time-to-peak with reduction of both ETP and peak height). In decompensated patients, bacterial infections and severity of anemia were associated with a further reduction of both ETP and peak height. CONCLUSION: Compensated cirrhosis is associated with an increased TG capacity. In decompensated cirrhosis, contrary to PPP-TG, which indicates hypercoagulability, WB-TG shows a significant hypocoagulable state. The clinical value of these findings deserves further investigation

Crucial roles of red blood cells and platelets in whole blood thrombin generation

Red blood cells (RBC) and platelets contribute to the coagulation capacity in bleeding and thrombotic disorders. The thrombin generation (TG) process is considered to reflect the interactions between plasma coagulation and the various blood cells. Using a new high-throughput method capturing the complete TG curve, we were able to compare TG in whole-blood and in autologous platelet-rich and platelet-poor plasma to redefine the blood cell contributions to the clotting process. We report a faster and initially higher generation of thrombin and a shorter coagulation time in whole blood than in PRP upon low concentrations of coagulant triggers, including tissue factor, Russell's viper venom factor X factor Xa, factor XIa and thrombin. The TG accelerated with increased hematocrit, and delayed after prior treatment of RBC with phosphatidylserine-blocking annexin A5. RBC treatment with ionomycin increased phosphatidylserine exposure, confirmed by flow cytometry, and enhanced the TG process. In reconstituted blood samples, annexin A5-blocked RBC allowed an enhanced glycoprotein VI-induced platelet procoagulant activity. In patients with anemia or erythrocytosis, cluster analysis revealed high or low whole-blood TG profiles in specific cases of anemia. All TG profiles lowered upon annexin A5 addition, and were thus determined by the extent of phosphatidylserine exposure of blood cells. Profiles for patients with polycythemia vera undergoing treatment were similar to control subjects. We concluded that RBC and platelets, in a phosphatidylserine-dependent way, contribute to the TG process. Determination of the whole-blood hypo-or hyper-coagulant activity may help to characterize a bleeding or thrombosis risk