Diaminobenzidine photoconversion is a suitable tool for tracking the intracellular location of fluorescently labelled nanoparticles at transmission electron microscopy.

Chitosan-based nanoparticles (NPs) deserve particular attention as suitable drug carriers in the field of pharmaceutics, since they are able to protect the encapsulated drugs and/or improve their efficacy by making them able to cross biological barriers (such as the blood-brain barrier) and reach their intracellular target sites. Understanding the intracellular location of NPs is crucial for designing drug delivery strategies. In this study, fluorescently-labelled chitosan NPs were administered in vitro to a neuronal cell line, and diaminobenzidine (DAB) photoconversion was applied to correlate fluorescence and transmission electron microscopy to precisely describe the NPs intracellular fate. This technique allowed to demonstrate that chitosan NPs easily enter neuronal cells, predominantly by endocytosis; they were found both inside membrane-bounded vesicles and free in the cytosol, and were observed to accumulate around the cell nucleus

Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity.

INTRODUCTION: Psoriasis is a chronic skin disorder associated with several comorbid conditions. In psoriasis pathogenesis, the role of some cytokines, including TNF-α and IL-17, has been elucidated. Beside their pro-inflammatory activity, they may also affect glucose and lipid metabolism, possibly promoting insulin resistance and obesity. On the other hand, adipose tissue, secreting adipokines such as chemerin, visfatin, leptin, and adiponectin, not only regulates glucose and lipid metabolism, and endothelial cell function regulation, but it may contribute to inflammation. AREAS COVERED: This review provides an updated 'state-of-the-art' about the reciprocal contribution of a small subset of conventional cytokines and adipokines involved in chronic inflammatory pathways, upregulated in both psoriasis and increased adiposity. A systematic search was conducted using the PubMed Medline database for primary articles. Expert commentary: Because psoriasis is associated with increased adiposity, it would be important to define the contribution of chronic skin inflammation to the onset of obesity and vice versa. Clarifying the pathogenic mechanism underlying this association, a therapeutic strategy having favorable effects on both psoriasis and increased adiposity could be identified

Differences in DNA methylation profile of Th1 and Th2 cytokine genes are associated with tolerance acquisition in children with IgE-mediated cow's milk allergy

Epigenetic changes in DNA methylation could regulate the expression of several allergy-related genes. We investigated whether tolerance acquisition in children with immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is characterized by a specific DNA methylation profile of Th2 (IL-4, IL-5) and Th1 (IL-10, IFN-γ)-associated cytokine genes

Influenza della sterilizzazione su strumenti fabbricati con leghe trattate termicamente

RiassuntoObiettiviDi recente sono stati proposti in endodonzia innovativi processi di produzione di leghe con trattamenti termici. Scopo di questo studio è stato di valutare l'effetto di vari cicli di sterilizzazione in autoclave sulla resistenza alla fatica ciclica di strumenti endodontici rotanti realizzati con leghe nichel-titanio (Ni-Ti) trattate termicamente.Materiali e metodiSono stati selezionati tre gruppi (n=24) di strumenti in Ni-Ti di taglia 04.40 K3, in lega Ni-Ti tradizionale, Vortex, in lega M-Wire e K3 XT prototipi in lega TF. Ogni gruppo è stato poi suddiviso in due sottogruppi (A e B) composti rispettivamente da strumenti non sterilizzati e strumenti sterilizzati in autoclave per 10 cicli a 134°. Tutti i 72 strumenti sono infine stati testati per fatica, valutando il numero di cicli a frattura (NCF). I dati sono stati raccolti e analizzati statisticamente (ANOVA).RisultatiGli strumenti K3 XT hanno mostrato una resistenza alla fatica ciclica significativamente maggiore (p<0,05) rispetto a tutti gli altri strumenti. Inoltre, sono state notate differenze statisticamente significative tra i file K3 XT sterilizzati e non sterilizzati (762 vs 651 NCF), mentre gli altri due tipi di strumento non hanno mostrato differenze rilevanti in seguito ai cicli di sterilizzazione (524 vs 539 K3, 454 vs 480 Vortex).ConclusioniPoiché i K3 e i K3 XT sono identici nel disegno e si differenziano solo per il trattamento termico, si può ipotizzare un'influenza positiva dell'apporto termico, come quello derivante da sterilizzazione in autoclave, in alcune leghe trattate termicamente.SummaryObjectivesRecently, innovative processes of production of alloys with thermal treatment have been proposed in endodontics. The aim of this study was to evaluate the effect of various cycles of autoclave sterilization on cyclic fatigue resistance of rotary endodontic instruments, made of heat-treated nickel-titanium (Ni-Ti) alloys.Materials and methodsThree groups (n=24) of Ni-Ti instruments with the same size (04.40) were selected: K3 (traditional Ni-Ti alloy), Vortex (M-Wire alloy) and K3 XT prototype (TF alloy). Each group was then divided into two subgroups comprising respectively non-sterilized instruments and instruments sterilized in an autoclave for 10 cycles at 134°. All 72 instruments were finally tested for fatigue, considering the number of cycles to fracture (NCF). Data were collected and analyzed statistically (ANOVA).ResultsThe instruments K3 XT showed significantly higher resistance to cyclic fatigue than all other instruments. Statistically significant differences (p<0.05) were also noted among the files K3 XT sterilized and unsterilized (762 vs 651 NCF), while the other two types of instrument did not show significant differences as a result of sterilization cycles (524 vs 539 K3, 454 vs 480 Vortex).ConclusionsGiven that K3 and K3 XT are identical in design and differ only in the heat treatment, a positive influence of heat treatment, such as the one caused by autoclaving, can be hypothesized

An Innovative, Open, Interoperable Citizen Engagement Cloud Platform for Smart Government and Users' Interaction

This paper introduces an open, interoperable, and cloud-computing-based citizen engagement platform for the management of administrative processes of public administrations, which also increases the engagement of citizens. The citizen engagement platform is the outcome of a 3-year Italian national project called PRISMA (Interoperable cloud platforms for smart government). The aim of the project is to constitute a new model of digital ecosystem that can support and enable new methods of interaction among public administrations, citizens, companies, and other stakeholders surrounding cities. The platform has been defined by the media as a flexible (enable the addition of any kind of application or service) and open (enable access to open services) Italian "cloud" that allows public administrations to access to a vast knowledge base represented as linked open data to be reused by a stakeholder community with the aim of developing new applications ("Cloud Apps") tailored to the specific needs of citizens. The platform has been used by Catania and Syracuse municipalities, two of the main cities of southern Italy, located in the Sicilian region. The fully adoption of the platform is rapidly spreading around the whole region (local developers have already used available application programming interfaces (APIs) to create additional services for citizens and administrations) to such an extent that other provinces of Sicily and Italy in general expressed their interest for its usage. The platform is available online and, as mentioned above, is open source and provides APIs for full exploitation.Comment: 23 pages, 7 figures, journal pape

Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study

AIM: To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy. METHODS: This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit. RESULTS: The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good. CONCLUSION: The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study—IL PSO (Italian landscape psoriasis)

Introduction: Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited

Ribociclib in newly diagnosed hepatitis B infection: A case report

Breast cancer is the most frequently diagnosed cancer in women worldwide. Actually CDK4/6 inhibitor Ribociclib is approved for the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer, but comorbidities like infectious or cardiovascular diseases may limit its use.Case reportA 45-year-old woman was diagnosed with metastatic breast cancer in September 2021; also, her hepatitis screening resulted positive for hepatitis B infection. Patient assumed eradicative therapy for hepatitis and bit after started oncological therapy with Ribociclib.OutcomeFrequent check of hepatological function was observed since start of eradicative therapy; liver transaminases and bilirubin kept to not rise despite start of oncological treatment with Ribociclib. Patient’s Performance Status was also not compromised and revaluation at 4, 9 and 13 months showed partial response and then stable disease.Discussionhepatotoxicity of Ribociclib is reported as a possible side effect, and often positivity for hepatitis is cause of exclusion from therapy; in our case, no hepatotoxicity was noted and patient obtained response in terms of control of both infectious and oncological diseases