An Interdisciplinary Approach for the Historical and Technical Characterization of Medieval and Modern Mortars

The study concerns Italian masonries and focuses on historical, medieval and modern mortars. Within the context of the different regions under examination (Piedmont, the Po Valley area, Latium, the Umbria-Marche region, and Apulia and Sardinia) a wide variety of materials with different chemical-physical characteristics were used in masonry work, determining different structural behaviors. The project aims at improving our knowledge about historical mortars in order to further the conservation of Italian built heritage, especially in zones with seismic risk. To achieve these results, we took samples and carried out analyses to investigate the different mechanical and cohesion properties that influence the vulnerability of ruined or collapsed structures. This information has enabled advances to be made in the prevention, maintenance, protection and preservation of historical buildings. Further details will concern the history of construction techniques, with particular regard to the relationship between local resources and construction sites. Another important topic is the role of different components and additives during the preparation of the mortars and their level of hydraulicity.Lo studio riguarda le strutture murarie in Italia e si concentra sulle malte storiche, medievali e moderne. Nei contesti regionali oggetto d’indagine (Piemonte e Pianura Padana, Lazio, Umbria-Marche, Puglia e Sardegna) è stata utilizzata una grande varietà di materiali, con caratteristiche chimico-fisiche diverse, e queste differenze determinano anche comportamenti strutturali diversi. Il progetto mira a migliorare la nostra conoscenza delle malte storiche per approfondire il tema della conservazione del patrimonio edilizio italiano, soprattutto nelle zone a rischio sismico. Per ottenere questi risultati, sono stati prelevati campioni sui quali sono state effettuate analisi per indagare quanto le diverse proprietà meccaniche e di coesione incidano sulla vulnerabilità delle strutture in rovina o collassate. Grazie a queste informazioni è stato possibile contribuire alla prevenzione, manutenzione, protezione e conservazione dell'edilizia storica. Ulteriori conoscenze hanno riguardato la storia delle tecniche di costruzione, con particolare riguardo al rapporto tra risorse locali e i cantieri. Un altro importante tema è stato il ruolo dei diversi componenti e additivi durante la preparazione delle malte e il loro livello di idraulicità

Mechanisms of atherothrombosis in chronic obstructive pulmonary disease

Patients affected by chronic obstructive pulmonary disease (COPD) have an increased risk of atherothrombotic acute events, independent of smoking and other cardiovascular risk factors. As a consequence, myocardial ischemia is a relevant cause of death in these patients. We reviewed studies concerning the potential mechanisms of atherothrombosis in COPD. Bronchial inflammation spreads to the systemic circulation and is known to play a key role in plaque formation and rupture. In fact, C-reactive protein blood levels increase in COPD and provide independent prognostic information. Systemic inflammation is the first cause of the hypercoagulable state commonly observed in COPD. Furthermore, hypoxia is supposed to activate platelets, thus accounting for the increased urinary excretion of platelet-derived thromboxane in COPD. The potential metabolic risk in COPD is still debated, in that recent studies do not support an association between COPD and diabetes mellitus. Finally, oxidative stress contributes to the pathogenesis of COPD and may promote oxidation of low-density-lipoproteins with foam cells formation. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by attenuating systemic inflammation, but this benefit needs confirmation in ongoing randomized controlled trials. Physicians approaching COPD patients should always be aware of the systemic vascular implications of this disease

In vivo morphological evaluation of the efficacy of an hydrogel conduit as scaffold for peripheral nerve regeneration

Autologous nerve grafting is considered the gold standard for bridging nerve lesion, although in several cases the use of artificial tubular guides is needed. Nowadays, the research is addressed to identify the ideal treatment able to support complete nerve regeneration and functional recovery. Therefore, the use of artificial synthetic or natural guides is required but, despite numerous studies on several kinds of conduits, the clinicians are still waiting for an alternative scaffolds giving the best regenerative properties. In this light, we evaluated in vivo the efficacy of a polyamidoamine-based hydrogel, shaped as small tubing for nerve regeneration. Studies were done on 3 experimental groups consisting of injured guide-implanted, sham operated and autograft rats (in which sciatic nerve was excised, inverted and re-implanted). In the implanted rats the sciatic nerve was transected and 5 mm gap between proximal and distal stumps was left in the middle of the conduit. Animals were then analyzed at 1, 3, 6, months post-surgery. The gait analysis and the thermal sensitivity analysis demonstrated movement improvement and sensitive recovery. The repaired, control and autograft nerves from all groups analyzed (implanted, sham and autograft) were processed for light microscopy and morphometric analysis. The axon size, myelin thickness and fiber density showed a complete nerve regeneration covering the gap in the central part of the conduit. In particular, the medial segment of the nerve tended to turn similar to sham operated (control) animals, while the autograft rats showed a less extensive regenerative process. Moreover, immunofluorescence analysis of longitudinal sections of the conduits were performed by labeling the axonal neurofilaments. The immunopositivity observed further confirmed that the regenerative process was complete, being the fibres present through the entire conduit between the proximal and the distal stumps. Overall, our data demonstrate that polyamidoamine-based hydrogel conduits are an implantable material providing a good support for the peripheral nerve regeneration. These conduits are biocompatible and biodegradable over the time to non toxic product metabolites. Finally our findings are promising for the achievement of implantable poliamidoamine- based hydrogel conduits functionalized for drug delivery with growth factors. This work has been supported by Fondazione CARIPLO under the Project “Functional Polymeric Hydrogels for Tissue Regeneration” (no. 2010-0501), call for the Scientific Research on Advanced Materials, 2010

Nuclear lipid microdomains regulate daunorubicin resistance in hepatoma cells

Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search for the role of nuclear lipid microdomains, rich in cholesterol and sphingomyelin, in drug resistance. We find that the daunorubicin induces perturbation of nuclear lipid microdomains, localized in the inner nuclear membrane, where active chromatin is anchored. As changes of sphingomyelin species in nuclear lipid microdomains depend on neutral sphingomyelinase activity, we extended our studies to investigate whether the enzyme is modulated by daunorubicin. Indeed the drug stimulated the sphingomyelinase activity that induced reduction of saturated long chain fatty acid sphingomyelin species in nuclear lipid microdomains. Incubation of untreated-drug cells with high levels of cholesterol resulted in the inhibition of sphingomyelinase activity with increased saturated fatty acid sphingomyelin species. In daunodubicin-treated cells, incubation with cholesterol reversed the action of the drug by acting via neutral sphingomyelinase. In conclusion, we suggest that cholesterol and sphingomyelin-forming nuclear lipid microdomains are involved in the drug resistance

Mutational Profile of Metastatic Breast Cancer Tissue in Patients Treated with Exemestane Plus Everolimus

Background. Everolimus has been shown to overcome endocrine resistance in hormone receptor positive advanced breast cancer patients. Predictive biomarkers of everolimus efficacy have been investigated in primary breast cancer tissue without finding univocal results. The goal of this study was to investigate the mutational burden in the metastatic site of endocrine-resistant tumors treated with everolimus plus exemestane. Patients and Methods. Mass Array Sequenom platform was used to analyse genetic status of 18 cancer-related genes in 25 archival tumor specimens from metastatic lesions and available primary matched breast cancer tissue of patients treated with everolimus and exemestane for advanced disease. An exploratory analysis of everolimus efficacy in terms of progression free survival benefit and single gene mutation was carried out. Results. The overall detection rate of mutation was 30% and 38% from metastatic and primary breast cancer samples, respectively. was the most frequent mutated gene. No primary breast cancer and matched relapse maintained the same mutation profile. Considering molecular pathways, the most of the genes belong to PI3K pathway (, , and ). In patients with detected mutations in breast and/or recurrence tissue the median PFS was 5,6 months while in the subgroup of patients with no mutations the median PFS was 7,5 months. Conclusions. The mutational status of breast cancer recurrence allows the identification of some genes potentially correlating tumor response/resistance to everolimus. The most frequently mutated genes were involved in the PI3K/AKT/mTOR pathway highlighting that the deregulation of this pathway in the relapse plays a crucial role in the mechanisms of everolimus resistance/sensitivity. Owing to the small sample size and the retrospective nature of the study, these correlations need to be validated in a large prospective study

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses.Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI]=14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI=8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4-3.8, p=0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1-2.7, p = 0.012), compared to patients treated with other DMTs.Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

Background Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5\u201310% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. Objectives To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. Methods Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II\u2013III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. Results Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II\u2013III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. Conclusion ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy

Epidemiology and clinical course of severe acute respiratory syndrome coronavirus 2 infection in cancer patients in the Veneto Oncology Network: The Rete Oncologica Veneta covID19 study

Introduction: Coronavirus disease 2019 (COVID-19) pandemic started in Italy with clusters identified in Northern Italy. The Veneto Oncology Network (Rete Oncologica Veneta) licenced dedicated guidelines to ensure proper care minimising the risk of infection in patients with cancer. Rete Oncologica Veneta covID19 (ROVID) is a regional registry aimed at describing epidemiology and clinical course of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer. Materials and methods: Patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on cancer diagnosis, comorbidities, anticancer treatments, as well as details on SARS-CoV-2 infection (hospitalisation, treatments, fate of the infection), have been recorded. Logistic regression analysis was applied to calculate the association between clinical/laboratory variables and death from any cause. Results: One hundred seventy patients have been enrolled. The median age at time of the SARS-CoV infection was 70 years (25-92). The most common cancer type was breast cancer (n = 40). The majority of the patients had stage IV disease. Half of the patients had two or more comorbidities. The majority of the patients (78%) presented with COVID-19 symptoms. More than 77% of the patients were hospitalized and 6% were admitted to intensive care units. Overall, 104 patients have documented resolution of the infection. Fifty-seven patients (33%) have died. In 29 cases (17%), the cause of death was directly correlated to SARS-CoV-2 infection. Factors significantly correlated with the risk of death were the following: Eastern Cooperative Oncology Group performance status (PS), age, presence of two or more comorbidities, presence of dyspnoea, COVID-19 phenotype ≥ 3, hospitalisation, intensive care unit admission, neutrophil/lymphocyte ratio and thrombocytopenia. Conclusions: The mortality rate reported in this confirms the frailty of this population. These data reinforce the need to protect patients with cancer from SARS-CoV-2 infection

The effectiveness of a school-based, universal mental health programme in six European countries

As children and young people today face ever increasing social, emotional and mental health challenges, schools, as one of the primary systems in children’s lives, are called to broaden their agenda and help to address these challenges. This paper discusses the evaluation of a school-based, universal mental health promotion programme developed recently for the European context. The programme provides a universal curriculum from early years to high school, aiming to promote social and emotional learning and resilience and prevent social, emotional, and behavioural problems in children and adolescents. A total of 7,789 students (and their teachers and parents) from kindergarten to high school across 6 countries in Europe were recruited from 434 classrooms in 124 schools, making use of cluster sampling. A quasi- experimental longitudinal design was used to evaluate the effectiveness of the programme on students’ outcomes by comparing the groups’ outcomes within times (pre-test vs. post-test) and between groups (experimental vs. control group). A total of 779 classroom teachers completed pre-and-post scales measuring students’ social and emotional learning, mental health and academic achievement. Results indicate that the experimental group had significantly larger increase in social and emotional competence and prosocial behaviour, and a decrease in mental health issues (externalising and internalising problems). No significant impact was found for academic outcomes. The findings are discussed in view of the limitations of the study and areas for further research.peer-reviewe