La pedagogia special nella sua azione educativa in contesti di inclusione

Risulta fondamentale definire chiaramente le parole e i concetti che si utilizzano quando si vogliono confrontare dei dati e mettere in atto un lavoro di ricerca-azione-formazione affinché i risultati e le verifiche siano comparabili. Un definire che non ha una necessità puramente nominalistica, ma utile e funzionale sia per orientare le ipotesi e le pratiche sia per poterle verificare in una dimensione comparativa. La definizione inoltre non va considerata come un dato assoluto ma va utilizzata solo e soltanto in relazione alla convenzione che un determinato gruppo decide in un sistema rigoroso come quello della ricerca e pertanto è suscettibile a permanenti modifiche concordate nell’itinerario del protocollo che si va via definendo nell’itinerario di ricerca-formazione-azione. La definizione quindi propone riferimenti non dogmatici, ma dinamici e flessibili, e rappresenta la sintassi e la grammatica di riferimento comune che nasce da ed in funzione di una cooperazione di più persone per il raggiungimento di un obiettivo condiviso all’interno di un sistema. Nel nostro caso intendo definire la particolarità della ricerca-formazione-azione (1) in relazione al raggiungimento di obiettivi circa l’autonomia e l’indipendenza di persone con necessità speciali (2)

Infections in breast implants: a review with a focus on developing Countries

The risk of surgical site infection is always present in surgery; the use of prosthetic materials is linked to an increased possibility of infection. Breast augmentation and breast reconstruction with implants are gaining popularity in developing countries. Implant infection is the main complication related to breast aesthetic and reconstructive surgery. In the present paper, we reviewed the current microbiological knowledge about implant infections, with particular attention to risk factors, diagnosis, clinical management, and antibiotic prophylaxis, focusing on reports from developing countries. After breast aesthetic surgery, up to 2.9% of patients develop a surgical site infection, with an incidence of 1.7% for acute infections and 0.8% for late infections. The rate of surgical site infection after post-mastectomy breast reconstruction is usually higher, ranging from 1% to 53%. The clinical features are not constant, and bacterial culture with antibiogram is the gold standard for diagnosis and for identification of antibiotic resistance. While waiting for culture results, empiric therapy with vancomycin and extended-spectrum penicillins or cephalosporins is recommended. Some patients require removal of the infected prosthesis. The main methods to bring down the risk of infection are strict asepsis protocol, preoperative antibiotic prophylaxis, and irrigation of the surgical pocket and implant with an antibiotic solution

Envejecer con síndrome de Down: una realidad que plantea nuevos retos

El curso "El envejecimiento de las personas con discapacidad intelectual", organizado del 22 al 26 de septiembre por la Universidad Internacional del Mar, en colaboración con Down España y Fundown, abordó las cuestiones principales de esta etapa vital para las personas con discapacidad intelectual. Los expertos, procedentes de diversas disciplinas académicas, acercaron a los asistentes a la realidad de las personas con síndrome de Down, a través de aspectos tan relevantes como la concepción de uno mismo, la familia, las necesidades afectivas, o el aprendizaje continuo

Tracing and tracking epiallele families in complex DNA populations

DNA methylation is a stable epigenetic modification, extremely polymorphic and driven by stochastic and deterministic events. Most of the current techniques used to analyse methylated sequences identify methylated cytosines (mCpGs) at a single-nucleotide level and compute the average methylation of CpGs in the population of molecules. Stable epialleles, i.e. CpG strings with the same DNA sequence containing a discrete linear succession of phased methylated/non-methylated CpGs in the same DNA molecule, cannot be identified due to the heterogeneity of the 5′–3′ ends of the molecules. Moreover, these are diluted by random unstable methylated CpGs and escape detection. We present here MethCoresProfiler, an R-based tool that provides a simple method to extract and identify combinations of methylated phased CpGs shared by all components of epiallele families in complex DNA populations. The methylated cores are stable over time, evolve by acquiring or losing new methyl sites and, ultimately, display high information content and low stochasticity. We have validated this method by identifying and tracing rare epialleles and their families in synthetic or in vivo complex cell populations derived from mouse brain areas and cells during postnatal differentiation

Rifaximin improves Clostridium difficile toxin A-induced toxicity in Caco-2 cells by the PXR-dependent TLR4/MyD88 /NF-?B pathway

Background: Clostridium difficile infections (CDIs) caused by Clostridium difficile toxin A (TcdA) lead to severe ulceration, inflammation and bleeding of the colon, and are difficult to treat. Aim: The study aimed to evaluate the effect of rifaximin on TcdA-induced apoptosis in intestinal epithelial cells and investigate the role of PXR in its mechanism of action. Methods: Caco‐2 cells were incubated with TcdA and treated with rifaximin (0.1−10 μM) with or without ketoconazole (10 μM). The transepithelial electrical resistance (TEER) and viability of the treated cells was determined. Also, the expression of zona occludens‐1 (ZO‐1), toll‐like receptor 4 (TLR4), Bcl‐2‐associated X protein (Bax), transforming growth factor‐β‐activated kinase‐1 (TAK1), myeloid differentiation factor 88 (MyD88) and nuclear factor‐kappaB (NF‐κB) was determined. Results Rifaximin treatment (0.1, 1.0 and 10 μM) caused a significant and concentration-dependent increase in the TEER of Caco-2 cells (360%, 480% and 680% vs TcdA treatment) 24 hours after the treatment and improved their viability (61%, 79% and 105%). Treatment also concentration-dependently decreased the expression of Bax protein (–29%, –65% and –77%) and increased the expression of ZO-1 (25%, 54% and 87%) and occludin (71%, 114% and 262%) versus TcdA treatment. The expression of TLR4 (–33%, –50% and –75%), MyD88 (–29%, –60% and –81%) and TAK1 (–37%, –63% and –79%) were also reduced with rifaximin versus TcdA treatment. Ketoconazole treatment inhibited these effects. Conclusions: Rifaximin improved TcdA‐induced toxicity in Caco‐2 cells by the PXR‐dependent TLR4/MyD88/NF‐κB pathway mechanism, and may be useful in the treatment of CDIs

Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway

Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 μM) in the presence or absence of ketoconazole (10 μM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 μM caused significant and concentration-dependent reduction of cell proliferation (-25, -40 and -68%), cell migration (-18, -30 and -46%) and PCNA expression (-29, -53 and -76%) in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion (-32, -45 and -72%), NO release (-40, -69 and -87%), VEGFR-2 expression (-33, -58 and -65%) and MMP-2 (-25, -62 and -87%) and MMP-9 expression (-38, -56 and -78%) vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt (-50, -75 and -86%), mTOR (-38, -56 and -78%), p38MAPK (-24, -62 and -71%) and inhibition of HIF-1α (-65, -82 and -92%), p70S6K (-27, -55 and -85%) and NF-κB (-29, -55 and -61%). Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool

Bacterial stimuli activate nitric oxide colonic mucosal production in diverticular disease. Protective effects ofL. casei DG® (Lactobacillus paracaseiCNCM I-1572)

Background: Micro-inflammation and changes in gut microbiota may play a role in the pathogenesis of diverticular disease (DD). Objective: The objective of this article is to evaluate the expression of nitric oxide (NO)-related mediators and S100B in colonic mucosa of patients with DD in an ex vivo model of bacterial infection. Methods: Intestinal biopsies obtained from patients with diverticulosis, symptomatic uncomplicated diverticular disease (SUDD) and SUDD with previous acute diverticulitis (SUDD+AD) were stimulated with the probiotic L. casei DG® (LCDG) and/or the pathogen enteroinvasive Escherichia coli (EIEC). S100B, NO release and iNOS expression were then evaluated. Results: Basal iNOS expression was significantly increased in SUDD and SUDD+AD patients. Basal NO expression was significantly increased in SUDD+AD. No differences in S100B release were found. In all groups, iNOS expression was significantly increased by EIEC and reduced by LCDG. In all groups, except for SUDD+AD, EIEC significantly increased NO release, whereas no increase was observed when LCDG was added to biopsies. EIEC did not induce significant changes in S100B release. Conclusions: Colonic mucosa of patients with DD is characterized by a different reactivity toward pathogenic stimuli. LCDG plays a role in counteracting the pro-inflammatory effects exerted by EIEC, suggesting a beneficial role of this probiotic in DD

SoK: Safer Digital-Safety Research Involving At-Risk Users

Research involving at-risk users -- that is, users who are more likely to experience a digital attack or to be disproportionately affected when harm from such an attack occurs -- can pose significant safety challenges to both users and researchers. Nevertheless, pursuing research in computer security and privacy is crucial to understanding how to meet the digital-safety needs of at-risk users and to design safer technology for all. To standardize and bolster safer research involving such users, we offer an analysis of 196 academic works to elicit 14 research risks and 36 safety practices used by a growing community of researchers. We pair this inconsistent set of reported safety practices with oral histories from 12 domain experts to contribute scaffolded and consolidated pragmatic guidance that researchers can use to plan, execute, and share safer digital-safety research involving at-risk users. We conclude by suggesting areas for future research regarding the reporting, study, and funding of at-risk user researchComment: 13 pages, 3 table

Prevalence of resistance-associated substitutions to NS3, NS5A and NS5B inhibitors at DAA-failure in hepatitis C virus in Italy from 2015 to 2019

: Despite the high efficacy of direct-acting antivirals (DAAs), the selection of resistance-associated substitutions (RASs) after virological failure of hepatitis C virus (HCV) DAAs can impair the cure of chronic HCV. The aim of the study was to characterize RASs after virological failure of DAAs in Italy over the years. Within the Italian network VIRONET-C, the change in prevalence of NS3/4A-NS5A-NS5B RASs was retrospectively evaluated in patients who failed a DAA regimen over the years 2015-2019. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols and the geno2pheno system was used to define HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend. Predictors of RASs at failure were analysed by logistic regression. Among 468 HCV-infected patients, HCV genotype 1 was the most prevalent (1b in 154, 33% and 1a in 109, 23%). DAA regimens were: ledipasvir (LDV)/sofosbuvir (SOF) in 131 patients (28%), daclatasvir (DCV)/SOF in 109 (23%), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) in 89 (19%), elbasvir (EBR)/grazoprevir (GRZ) in 52 (10.5%), velpatasvir (VEL)/SOF in 53 (11%), glecaprevir (GLE)/pibrentasvir (PIB) in 27 (6%) and ombitasvir/paritaprevir/ritonavir (2D) in 7 (1.5%); ribavirin was administered in 133 (28%). The NS5A fasta sequence was available for all patients, NS5B and NS3/4A both for 93%. The prevalence of NS5A and NS3/4A RASs significantly declined from 2015 to 2019; NS5B RAS remained stable. Independent predictors of any RASs included older age and genotype 1a (vs G2 and vs G4). Notably, at least partial susceptibility to all the agents included in the GLE/PIB and VEL/SOF/Voxilaprevir (VOX) combinations was predicted in >95% of cases. As RASs remain common at the failure of DAAs, their identification could play a crucial role in optimizing re-treatment strategies. In Italy RAS prevalence has been decreasing over the years and susceptibility to the latest developed drug combinations is maintained in most cases