Phosphine Oxide Indenoquinoline Derivatives: Synthesis and Biological Evaluation as Topoisomerase I Inhibitors and Antiproliferative Agents.

The synthesis of phosphorous indenoquinolines and their biological evaluation as topoisomerase 1 (TOP1) inhibitors and antiproliferative agents were performed. First, the preparation of new hybrid 5-indeno[2,1-]quinolines with a phosphine oxide group was performed by a two-step Povarov-type [4+2]-cycloaddition reaction between the corresponding phosphorated aldimines with indene in the presence of BF·EtO. Subsequent oxidation of the methylene present in the structure resulted in the corresponding indeno[2,1-]quinolin-7-one phosphine oxides .

Impella CP-Assisted Balloon Aortic Valvuloplasty in 2 High-Risk Patients.

Balloon aortic valvuloplasty (BAV) is a therapeutic option as palliative or bridging therapy in severe aortic stenosis, even though it is a risky procedure, especially in patients with concomitant left ventricular dysfunction. The use of percutaneous ventricular assist devices, such as the Impella CP, in this scenario provides optimal circulatory support and considerably reduces the risk of the procedure. Two patients with severe aortic stenosis and left ventricular dysfunction underwent BAV with the support of the Impella-CP.

Role of canonical and non-canonical cAMP sources in CRHR2α-dependent signaling.

Hippocampal neurons exhibit activation of both the conventional transmembrane adenylyl cyclases (tmACs) and the non-canonical soluble adenylyl cyclase (sAC) as sources of cyclic AMP (cAMP). These two cAMP sources play crucial roles in mediating signaling pathways downstream of CRHR1 in neuronal and neuroendocrine contexts. In this study, we investigate the involvement of both cAMP sources in the molecular mechanisms triggered by CRHR2α.

Dysregulated neutrophil extracellular traps and haemostatic biomarkers as diagnostic tools and therapeutic targets in periprosthetic joint infection.

Aims: Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods: We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma.