The silent survival of Staphylococcus aureus phagocyted by HL-60 derived neutrophils

Staphylococcus aureus is a Gram positive pathogen that causes various human infections and represents one of the most common causes of bacteremia. S. aureus is able to invade a variety of non-professional phagocytes and that can survive engulfment by neutrophils, producing both secreted and surface components that compromise innate immune responses. In the contest of our study we evaluated the functional activity of vaccine specific antibodies by opsonophagocytosis killing assay (OPKA). Interestingly a low level of killing of the staphylococcal cells has been observed. In the meanwhile intracellular survival studies showed that S. aureus persisted inside phagocytes for several hours until a burst of growth after 5 hours in the supernatant. These data suggest that the strong ability of S. aureus to survive in the phagocytes could be the cause of the low killing measured by OPKA. Moreover parallel studies on HL-60 cells infected with S. aureus done by using transmission electron microscopy (TEM) interestingly showed that staphylococcal cells have an intracellular localization (endosomal vacuoles) and that they are able not only to maintain the integrity of their membrane but also to replicate inside vacuolar compartments. Finally in order to generate 3D volume of whole bacteria when present inside neutrophilic vacuoles, we collected a series of tomographic two-dimensional (2D) images by using a transmission electron microscope, generating 5 different tomograms. The three-dimensional reconstruction reveals the presence of intact bacteria within neutrophil vacuoles. The S. aureus membrane appears completely undamaged and integral in contrast with the physiological process of phagosytosis through vacuoles progression. S. aureus bacteria show a homogenous distribution of the density in all the three dimensions (X, Y, Z). All these evidences definitely explain the ability of the pathogen to survive inside the endosomal vacuoles and should be the cause of the low killing level.

Principi di simmetria nella formulazione del modello standard. Riflessioni per una proposta didattica sulla fisica dei primi anni '60

Obiettivo della tesi è sviluppare riflessioni per una proposta d’insegnamento inerente episodi significativi nella formulazione del Modello Standard e rivolta principalmente a studenti universitari del corso magistrale di “Storia della fisica”. Il lavoro di tesi è incentrato su un’analisi di articoli originali degli anni ’60, mirata a evidenziare il significato assunto dalla simmetria nella fisica del XX e XXI secolo, ovvero quello di principio alla base della formulazione di teorie fisiche; nello specifico, ci si è focalizzati sull’analisi di un episodio di particolare interesse culturale nella storia della fisica: la formulazione dell’ Eightfold Way (“Via dell’Ottetto”) sulla base del gruppo di simmetria SU(3) e la conseguente ipotesi sull'esistenza dei quark.

Oswald Mathias Ungers: Belvederestraße 60. Zu einer neuen Archtektur.

La presente Tesi di Dottorato intende affrontare una lettura critica della Casa in Belvederestraße 60, realizzata dall’architetto Oswald Mathias Ungers (Kaisersesch, 12 luglio 1926 – Köln, 30 settembre 2007), nel 1958-’59 a Köln-Müngersdorf, come studio per sé ed abitazione per la propria famiglia. Questo primo oggetto della ricerca viene considerato evidente espressione delle convinzioni formali e compositive dell’architetto, negli anni Cinquanta e Sessanta. A differenza di altri progetti residenziali coevi ed antecedenti, frutto di un’elaborazione autonoma, la prima casa che costruisce per sé riflette una maggiore libertà di pensiero, dettata dalla coincidenza delle figure di progettista e committente; a ciò si aggiunge anche una precisa volontà dichiarativa ed ideologica. Proprio quest’ultimo aspetto permette di introdurre il secondo oggetto della Tesi: il manifesto “ideologico”, Zu einer neuen Architektur, scritto dallo stesso Oswald Mathias Ungers e da Reinhard Gieselmann, alla fine del 1960; un breve testo che espone, con toni perentori ed inappellabili, il punto di vista dei due architetti nei confronti di un panorama architettonico e critico, caratterizzato da una sterilità di pensiero dilagante, a causa dell’egemonia costruttiva funzionalista. La ricerca indaga quindi le forti reciprocità delle due opere: casa e testo, viste in chiave di “manifesto scritto e manifesto costruito”. Il primo legame tra i due soggetti è senza dubbio la concomitanza temporale, (tra il 1958 ed il 1960) associata ad un rapporto causa-effetto, tale per cui il manifesto viene redatto a difesa delle aspre critiche scaturite dalla pubblicazione della casa sulla rivista Bauwelt. Il secondo nesso è la possibilità di comprendere le accezioni effettive dei termini impiegati nella redazione del testo, attraverso le forme di una delle opere maggiormente personali dell’architetto, estraendone il senso e conferendogli un’immagine architettonica. Si vuole creare così un rapporto biunivoco di traducibilità, dell’architettura nello scritto e della semantica ungersiana in azioni compositive.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

Ten-year comparison of pericardial tissue valves versus mechanical prostheses for aortic valve replacement in patients younger than 60 years of age

Aortic valve replacement using a tissue valve is controversial for patients younger than 60 years old. The long-term survival in this age group, the expected event rates during long-term follow-up, and valve-related complications are not clearly determined.

Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.