Evaluating the Impacts of Alcohol-Based Solutions on Silk: Chemical, Mechanical and Wettability Changes before and after Artificial Ageing

Due to the COVID-19 pandemic, since 2020, alcohol-based sanitisers have been frequently used in museums and historic sites. Although they provide a safer environment for visitors, the impact of the (components in) sanitisers on the cultural heritage on open display is still uncertain. The current study investigated the effects of ethanol and isopropanol solutions on silk artefacts specifically in relation to possible mechanical changes and to their long-term impact based on artificial ageing. Thus, samples from three modern silk fabrics were treated through spraying and immersion with six solutions, two of which contained benzalkonium chloride (BZK), a surfactant suggested by Italian national guidelines in the formulation of sanitisers for museums. The impact of the treatment was studied from a chemical perspective, i.e., through spectroscopic techniques, and considering changes in the mechanical strength through uniaxial tensile testing. In addition, water wettability was measured. To study whether the contact with the solutions can affect the degradation path of silk, after the treatment, samples were exposed to light ageing and were stored at medium and high RH, i.e., 55% and 80%. Furthermore, treated and untreated silk textiles were placed in the Museum of Palazzo Mocenigo (Venice) to define the behaviour in an actual museum environment. The results show that, even when silk is immersed in the solutions for 180 min, no relevant chemical and physical changes can be observed on silk fibres. Variations noted at the end of the light ageing occurred regardless of the treatments with the solutions, so they are not affected by the contact with sanitisers. Nevertheless, when treating the samples (also through spraying) with solutions containing BZK, the surfactant is adsorbed by the textile. Once adsorbed, BZK significantly increases the water wettability of silk, causing a persistent modification of the property as also observed at the end of the ageing and in situ tests

Is the experience mutation of G-CSF truly a predictive indicator of trends in early myolodysplasia or leukemia?

La neutropenia congenita grave (NCG) è un disturbo eterogeneo della mielopoiesi caratterizzato da valori di neutrofili costantemente <500/mm3, con arresto maturativo a livello dei promielociti, alta incidenza di infezioni batteriche, fatali in era pre-G-CSF. Con l’introduzione del trattamento con G-CSF, la prognosi della malattia, come sopravvivenza e qualità di vita, è radicalmente cambiata mentre l’evoluzione in MDS/AML, descritta anche in era pre-G-CSF, è diventata più frequente. Dai dati del Severe Chronic Neutropenia International Registry l’incidenza cumulativa di MDS/AML in pazienti con NCG dopo un trattamento di 10 anni è del 21%. La comparsa di mutazioni puntiformi del gene per il recettore del G-CSF (GCSF-R), insieme alla comparsa di alterazioni citogenetiche, è stata messa in relazione con l’evoluzione in MDS/AML. Descriviamo una paziente che, a circa 7 anni dalla comparsa di mutazione del GCSF-R, non ha evidenziato segni di evoluzione in MDS/AML. MV, nata il 16/06/81, affetta da NCG con mutazione ELA2 458 T>C, trattata con G-CSF dal 1990 alla dose media di 1.9 microgr/kg/die, con neutrofili mantenuti tra 1500-2000/mm3 e buon controllo delle infezioni; follow-up annuale con mieloaspirato, BOM, citogenetica (FISH con ibridizzazione in situ per asat cr7, 8 e LSI 21) e screening molecolare (CBFB-MYH11, AML1- ETO, PML-RARA). Dal 1999 ha anche effettuato, in occasione di ogni prelievo di sangue midollare, ricerca di mutazioni acquisite di GCSF-R. Nel dicembre 2001, attraverso l’analisi di sequenza del cDNA della porzione intracellulare del gene CSF3R clonato, è stata individuata la mutazione puntiforme acquisita 2390C>T. La mutazione è stata confermata in occasione degli ulteriori controlli. In considerazione delle segnalazioni di aumentato rischio di evoluzione in MDS/AML dopo comparsa di mutazione del GCSF-R, è stato condotto un follow up con mieloaspirato, BOM e valutazione citogenetica ogni 6 mesi. La indicazione ad eseguire un TCSE allogenico non risultata applicabile per mancanza di un donatore compatibile familiare o volontario. Ad oggi non è stata documentata la comparsa di ulteriori mutazioni del GCSF-R, né di alterazioni citogenetiche; da un punto di vista morfologico, la valutazione del mieloaspirato e della BOM non hanno mostrato segni di evoluzione in mielodisplasia/AML. La osservazione di casi come questo potrebbe rimettere in discussione la attuale indicazione al TCSE sulla base della sola comparsa di mutazioni di GCSFR

Minimal Residual Disease assessment based on IgH rearrangements and flow cytometry in canine Diffuse Large B-cell Lymphoma

Introduction Canine diffuse large B-cell lymphoma (cDLBCL) accounts for 30-40% of lymphoma cases. The persistence of cells unidentifiable through cytology is termed Minimal Residual Disease (MRD). Currently, MRD is measured by flow-cytometry (FC). The aim of the study was to determine the diagnostic and prognostic role of rearranged IgH (PARR analysis) in the lymph node (LN), peripheral blood (PB) and bone marrow (BM) in cDLBCL compared with FC. Materials and methods PB, BM aspirate and LN tissue from 17 DLBCL were available for PARR analysis at diagnosis (T0) and at the end of treatment (T1). The concordance between PARR and FC was analyzed for LN, PB and BM. Results At T0, the B-cell origin of the lymphomas was confirmed by IgH Major rearrangements in the LN of all dogs. Eleven dogs (64.7%) showed simultaneous IgH rearrangements in BM and PB, whereas 6 dogs (35.3%) had no rearrangements in none of the samples. At T1, IgH monoclonal rearrangement was found in 13 (81%), 8 (50%) and 6 dogs (38%) in LN, PB and BM, respectively. At T0, the concordance rate between FC and PARR was 100%, 82% and 47% for LN, PB and BM, respectively. The highest concordance rate was obtained in LNs (PARR-positive/FC-positive), whereas the highest discordance was obtained in BM (PARR-positive/FC-negative). At T1, the concordance rate was overall reduced, accounting for 47%, 50%, and 63% in LN, PB and BM, respectively. The highest discordance rate was found in LNs (PARR-positive/FC-negative), whereas the highest concordance was found in BM (PARR-negative/FC-negative). Discussion We propose the use of both, PARR and FC, in tandem to offset the possibility of false-negative MRD assessment; in case of discrepant results, dogs should be closely monitored to detect a possible early recurrence. The concordance rate was largely dependent on the time point, being higher in T0. The discordance between PARR and FC results in dogs in clinical remission may be due to the limited number of available cells, which reduces the sensitivity of FC

MHV-68 producing mIFNα1 is severely attenuated in vivo and effectively protects mice against challenge with wt MHV-68.

Human gammaherpesviruses such as Epstein-Barr virus (EBV) cause lifelong infections and associated diseases, by virtue of their ability to establish latent infection. Many studies performed in the past years in murine herpesvirus 68 (MHV-68) model of infection suggested that the limited immunity generated against isolated viral components by subunit vaccines cannot counteract the multiple immune evasion strategies operated by gammaherpesviruses. Indeed, a significant inhibition of long-term latency establishment could be observed in mice vaccinated with strains of genetically modified MHV-68 defective in reactivation or establishment of latency. In this study, we focused on the effects of interferon-α (IFN-α) on both the lytic and latent phase of MHV-68 infection, as exerted by the constitutive release of IFN-α1 by a clone of MHV-68 genetically modified to produce this cytokine (MHV-68mIFNα1). Although the MHV-68mIFNα1 recombinant virus exhibited in vitro replication features indistinguishable from those of the wild type MHV-68, its pathological properties were severely attenuated in vivo in immunocompetent mice and not in mice rendered genetically unresponsive to type I IFN, suggesting that a stronger immune response was primed in the presence of the cytokine. Notably, MHV-68mIFNα1 attenuation did not result in a reduced level of long-term spleen latency establishment. These results prompted us to evaluate the efficacy of MHV-68mIFNα1 in a prophylactic vaccination regimen aimed at inhibiting the symptoms of acute virus infection and the establishment of long-term latency after MHV-68 challenge. Our results show that mice vaccinated with MHV-68mIFNα1, administered as a live-attenuated or partially inactivated (by Psoralen and UV treatment) vaccine, were protected against the challenge with wt MHV-68 from all phases of infection. The ability of MHV-68mIFNα1 to produce IFN-α at the site of the infection, thus efficiently stimulating the immune system in case of virus reactivation from latency, makes this recombinant virus a safer live-attenuated vaccine as compared to the previously reported latency-deficient clones. © 2011 Elsevier Ltd

Minimal residual disease detection by flow cytometry and PARR in lymph node, peripheral blood and bone marrow, following treatment of dogs with diffuse large B-cell lymphoma

The most promising techniques for detecting minimal residual disease (MRD) in canine lymphoma are flow cytometry (FC) and polymerase chain reaction amplification of antigen receptor genes (PARR). However, the agreement between these methods has not been established. MRD was monitored by FC and PARR following treatment of dogs affected with diffuse large B-cell lymphoma (DLBCL), comparing results in lymph node (LN), peripheral blood (PB) and bone marrow (BM) samples. The prognostic impact of MRD on time to relapse (TTR) and lymphoma-specific survival (LSS) was also assessed. Fourteen dogs with previously untreated DLBCL were enrolled into the study; 10 dogs eventually relapsed, while four dogs with undetectable MRD were still in remission at the end of the study. At diagnosis, the concordance rate between FC and PARR was 100%, 78.6%, and 64.3% for LN, PB and BM, respectively. At the end of treatment, the agreement rates were 35.7%, 50%, and 57.1% for LN, PB and BM, respectively. At least one of the follow-up samples from dogs experiencing relapse was PARR(+); conversely, FC was not able to detect MRD in seven of the dogs that relapsed. PARR was more sensitive than FC in predicting TTR, whereas the combination of PARR and FC was more sensitive than either technique alone in predicting LSS using PB samples. The results suggest that immunological and molecular techniques should be used in combination when monitoring for MRD in canine DLBCL