Recovering the lost context of the Roverella altarpiece by Cosmè Tura. The Olivetan church of San Giorgio fuori le mura in Ferrara

This thesis aims to recover the original context of the Pala Roverella by Cosmè Tura, rightly considered the apex of the Ferrarese figurative culture of the late Quattrocento. The Olivetan conventual church of San Giorgio fuori le mura in Ferrara, the ancient cathedral of Ferrara, has been so far overlooked by Renaissance scholars. By piecing together elements derived from various sources (the church fabric itself, notarial acts, local chronicles and church descriptions, as well as sixteenth century visual records) we formulate here a hypothesis on the late-Gothic San Giorgio. Chapter One offers a survey of art patronage in Ferrarese churches in the second half of the fifteenth century. Chapter Two focuses on San Giorgio in the Quattrocento. New documents shed light on the history of the church and its benefactors, including the Lucchese businessman Aliprando Guidiccioni and members of the Savonarola family. Unpublished sources are used to recreate the broader context of the Pala Roverella, including liturgical items and illuminated manuscripts. Chapter Three is devoted to the Roverella family and their important role as patrons in San Giorgio in the 1470s and 1480s. By reconsidering the tomb of Lorenzo Roverella, still in the cappella maggiore of San Giorgio, we provide new elements about one of its two authors, Ambrogio da Milano. Chapter Four focuses on the surviving paintings from the Roverella altarpiece. Their reassessment provides new elements about its iconography, dating and location. Chapter Five is devoted to the renovations of San Giorgio from the late sixteenth to the early eighteenth centuries. By following the history of the fabric we gather useful clues for our reconstruction of the fifteenth-century church. The Appendix contains transcriptions of relevant documents, most of them unpublished

BDNF/TrkB axis activation promotes epithelial-mesenchymal transition in idiopathic pulmonary fibrosis

Background: Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts. Methods: Lung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls. Results: BDNF treatment promoted mesenchymal differentiation and this effect was counteracted by the TrkB inhibitor K252a. In this regard, we showed that K252a treatment was able to control the expression of transcription factors involved in epithelial to mesenchymal transition (EMT). Accordingly, K252a treatment reduced matrix metalloproteinase-9 enzyme activity and E-cadherin expression while increased cytoplasmic β-catenin expression. Conclusions: Our results suggest that BDNF/TrkB axis plays a role in EMT promoting the acquisition of (myo)fibroblast cell phenotype in IPF. Targeting BDNF/TrkB seems to represent a viable approach in order to prevent EMT dependent lung fibrosis

Flash Glucose Monitoring: A Review of the Literature with a Special Focus on Type 1 Diabetes

In people with type 1 diabetes mellitus (T1DM), obtaining good glycemic control is essential to reduce the risk of acute and chronic complications. Frequent glucose monitoring allows the adjustment of insulin therapy to improve metabolic control with near-normal blood glucose concentrations. The recent development of innovative technological devices for the management of T1DM provides new opportunities for patients and health care professionals to improve glycemic control and quality of life. Currently, in addition to traditional self-monitoring of blood glucose (SMBG) through a glucometer, there are new strategies to measure glucose levels, including the detection of interstitial glucose through Continuous Glucose Monitoring (iCGM) or Flash Glucose Monitoring (FGM). In this review, we analyze current evidence on the efficacy and safety of FGM, with a special focus on T1DM. FGM is an effective tool with great potential for the management of T1DM both in the pediatric and adult population that can help patients to improve metabolic control and quality of life. Although FGM might not be included in the development of an artificial pancreas and some models of iCGM are more accurate than FGM and preferable in some specific situations, FGM represents a cheaper and valid alternative for selected patients. In fact, FGM provides significantly more data than the intermittent results obtained by SMBG, which may not capture intervals of extreme variability or nocturnal events. With the help of a log related to insulin doses, meal intake, physical activity and stress factors, people can achieve the full benefits of FGM and work together with health care professionals to act upon the information provided by the sensor. The graphs and trends available with FGM better allow an understanding of how different factors (e.g., physical activity, diet) impact glycemic control, consequently motivating patients to take charge of their health

UPDATING THE TAXONOMY AND DISTRIBUTION OF THE EUROPEAN OSMODERMA, AND STRATEGIES FOR THEIR CONSERVATION (COLEOPTERA, SCARABAEIDAE, CETONIINAE)

Results of a molecular analysis on the European hermit beetles (the Osmoderma eremita species-complex), recently published in a companion paper, are shortly dis- cussed and commented. These results indicate a clear-cut distinction between two clades. The first one includes the W-European O. eremita Scopoli, 1763, and the two Italian endemic taxa O. italicum Sparacio, 2000 and O. cristinae Sparacio, 1994, from southern peninsular Italy and Sicily, respectively. The second one includes the widespread E-European O. barnabita Motschulsky, 1845 (nom. resurr.), and the southern Balcanic O. lassallei Baraud & Tauzin, 1991 from Greece and European Turkey. Within the two clades, molecular data well support a specific rank for O. lassallei and O. barn­abita on one side, and of O. eremita and O. cristinae on the other side, while the taxonomic position of O. italicum, more closely related with O. eremita, is still uncertain, waiting for analysis of additional specimens of this very rare taxon. Current geographical distribution, interspecific genetic diversification, and relatively low levels of intraspecific genetic divergence in O. eremita sensu stricto, are hypothesized to be the result of multiple speciation events (mainly occurred in refugial forest areas of the Italian and Balkan peninsulas and Sicily before and during the Pleistocene glacial peaks), followed by fast post-glacial northward and westward expansion of some species. The need of further genetic data on the rare and threatened hermit beetle species and the importance of more detailed information on their distribution ranges are emphasized and discussed, in order to plan conservation strategies in the near future. An updated worldwide checklist of the species of the genus Osmoderma is finally presented

UPDATING THE TAXONOMY AND DISTRIBUTION OF THE EUROPEAN OSMODERMA, AND STRATEGIES FOR THEIR CONSERVATION (Coleoptera, Scarabaeidae, Cetoniinae)

Results of a molecular analysis on the European hermit beetles (the Osmoderma eremita species-complex), recently published in a companion paper, are shortly dis- cussed and commented. These results indicate a clear-cut distinction between two clades. The first one includes the W-European O. eremita Scopoli, 1763, and the two Italian endemic taxa O. italicum Sparacio, 2000 and O. cristinae Sparacio, 1994, from southern peninsular Italy and Sicily, respectively. The second one includes the widespread E-European O. barnabita Motschulsky, 1845 (nom. resurr.), and the southern Balcanic O. lassallei Baraud & Tauzin, 1991 from Greece and European Turkey. Within the two clades, molecular data well support a specific rank for O. lassallei and O. barn­abita on one side, and of O. eremita and O. cristinae on the other side, while the taxonomic position of O. italicum, more closely related with O. eremita, is still uncertain, waiting for analysis of additional specimens of this very rare taxon. Current geographical distribution, interspecific genetic diversification, and relatively low levels of intraspecific genetic divergence in O. eremita sensu stricto, are hypothesized to be the result of multiple speciation events (mainly occurred in refugial forest areas of the Italian and Balkan peninsulas and Sicily before and during the Pleistocene glacial peaks), followed by fast post-glacial northward and westward expansion of some species. The need of further genetic data on the rare and threatened hermit beetle species and the importance of more detailed information on their distribution ranges are emphasized and discussed, in order to plan conservation strategies in the near future. An updated worldwide checklist of the species of the genus Osmoderma is finally presented

Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH.

Background: Conventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%. Results: In a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb). FISH analysis could be performed on six cases and showed that rearrangements were translocation derivatives, indistinguishable from a normal karyotype as they involved a similar band pattern and size. Five were inherited from a parent with a balanced translocation, whereas two were apparently de novo. Genes spanning the rearrangements could be associated with some phenotypic features in three cases (case 3: DOCK8; case 4: GATA3, AKR1C4; case 6: AS/PWS deletion, CHRNA7), and in two, likely disease genes were present (case 5: NR2F2, TP63, IGF1R; case 7: CDON). Three of our cases were prenatal diagnoses with an apparently normal karyotype. Conclusions: Large complex rearrangements of up to 18 Mb, involving chromosomal regions with similar size and band appearance may be overlooked by conventional karyotyping. Array-CGH allows a precise chromosomal diagnosis and recurrence risk definition, further confirming this analysis as a first tier approach to clarify molecular bases of ID/DD and/or MCA. In prenatal tests, array-CGH is confirmed as an important tool to avoid false negative results due to karyotype intrinsic limit of detection

IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL

Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications

Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to >11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19–86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors