Minimal modulation of the host immune response to SIS matrix implants by mesenchymal stem cells from the amniotic fluid

Surgical restoration of soft tissue defects often requires implantable devices. The clinical outcome of the surgery is determined by the properties inherent to the used matrix. Mesenchymal stem cells (MSC) modulate the immune processes after in vivo transplantation and their addition to matrices is associated with constructive remodeling. Herein we evaluate the potential of MSC derived from the amniotic fluid (AF-MSC), an interesting MSC source for cell therapeutic applications in the perinatal period, for immune modulation when added to a biomaterial.status: publishe

Necrosome complex detected in granulovacuolar degeneration is associated with neuronal loss in Alzheimer's disease

Alzheimer's disease (AD) is characterized by a specific pattern of neuropathological changes, including extracellular amyloid β (Aβ) deposits, intracellular neurofibrillary tangles (NFTs), granulovacuolar degeneration (GVD) representing cytoplasmic vacuolar lesions, synapse dysfunction and neuronal loss. Necroptosis, a programmed form of necrosis characterized by the assembly of the necrosome complex composed of phosphorylated proteins, i.e. receptor-interacting serine/threonine-protein kinase 1 and 3 (pRIPK1 and pRIPK3) and mixed lineage kinase domain-like protein (pMLKL), has recently been shown to be involved in AD. However, it is not yet clear whether necrosome assembly takes place in brain regions showing AD-related neuronal loss and whether it is associated with AD-related neuropathological changes. Here, we analyzed brains of AD, pathologically defined preclinical AD (p-preAD) and non-AD control cases to determine the neuropathological characteristics and distribution pattern of the necrosome components. We demonstrated that all three activated necrosome components can be detected in GVD lesions (GVDn+, i.e. GVD with activated necrosome) in neurons, that they colocalize with classical GVD markers, such as pTDP-43 and CK1δ, and similarly to these markers detect GVD lesions. GVDn + neurons inversely correlated with neuronal density in the early affected CA1 region of the hippocampus and in the late affected frontal cortex layer III. Additionally, AD-related GVD lesions were associated with AD-defining parameters, showing the strongest correlation and partial colocalization with NFT pathology. Therefore, we conclude that the presence of the necrosome in GVD plays a role in AD, possibly by representing an AD-specific form of necroptosis-related neuron death. Hence, necroptosis-related neuron loss could be an interesting therapeutic target for treating AD

L’attività dei Centri Antifumo italiani tra problematiche e aree da potenziare: i risultati di un’indagine svolta attraverso un questionario on-line

Introduzione. In Italia sono 295 i Servizi per la cessazione dal fumo di tabacco (Centri Antifumo - CA) afferenti al Servizio Sanitario Nazionale (SSN) censiti nel 2011 dall’Osservatorio Fumo, Alcol e Droga (OssFAD) dell’Istituto Superiore di Sanità. La presente indagine, condotta dall’OssFAD in collaborazione con i CA, è stata volta a rilevare alcune delle problematiche con le quali il personale dei CA si confronta per portare avanti la propria attività e le iniziative ritenute utili per migliorarla. Materiali e metodi. L’indagine è stata condotta dal 7 al 21 maggio 2012, mediante un questionario compilabile on-line composto da 5 brevi sezioni di domande con un totale di 38 items da completare. Il link al questionario on-line è stato inviato per e-mail a 322 indirizzi dei CA censiti nel 2011 dall’OssFAD. I dati raccolti sono stati elaborati statisticamente con il programma SPSS 20. Risultati. All’indagine hanno risposto 146 operatori dei CA (45,3%). Sebbene ci siano aspetti ormai consolidati dell’attività dei CA, sono ancora molte le criticità che gli operatori riscontrano nella loro attività. Le principali problematiche che influiscono in modo fondamentale/rilevante per la buona attività del centro sono le “Scarse o nulle risorse economiche” per il 60,7% del personale, “la mancanza di personale dedicato” per il 52,4% del personale; il “riconoscimento/mandato istituzionale del CA” per il 40,9% del personale. Tra le azioni ritenute più efficaci per facilitare l’accesso ai CA sono risultate la sensibilizzazione del personale sanitario (91%), in particolare dei medici di famiglia e l’inserimento delle prestazioni antitabagiche nei LEA (76,8%). Conclusioni. È auspicabile che l’attività dei CA riceva una maggiore attenzione, attraverso la dotazione di strutture, personale e finanziamenti adeguati a svolgere un importante ruolo nella tutela e promozione della salute

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management