LPS and Conditioned Medium Enhance the Release of a Low Molecular Weight, Transcriptionally Active, Fragment of Glycogen Synthase-3 Kinase in IMR-32 Cell Line.

Background: Glycogen synthase-3 kinase (GSK3) is one of the major contributors of tau hyperphosphorylation linked to neurofibrillary tangles in Alzheimer's disease (AD).

Objective: To determine a mechanism of GSK-3β activation by two periodontal bacteria consistently confirmed in AD autopsied brains.

Methods: FDC381 and ATCC10301 conditioned media were collected.

Real life clinical outcomes of relapsed/refractory diffuse large B cell lymphoma in the rituximab era: The STRIDER study.

Background: Relapse and refractory (R/R) rates after first-line R-CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively.

Aims: We conducted a retrospective real-world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients.

Material And Methods: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed.

Long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma achieving a complete response with pixantrone.

Introduction: The prognosis of diffuse large B-cell lymphoma (DLBCL) patients with refractory or multiply relapsed (R/R) disease is disappointing. Pixantrone is currently approved as third or fourth line regimen, with encouraging results, even if long-term follow-up data are limited.

Methods: In this post-hoc analysis of our observational study, we retrospectively investigated disease outcome and clinical characteristics of 16 R/R DLBCL patients who achieved a complete response with pixantrone.

Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options.

Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein-Barr virus (EBV) infection is present in 60-80% of the cases, revealing the central role played by the latent infection in the pathogenesis of the disease. Therefore, EBV serological status is considered the most important risk factor associated with PTLDs, together with the depth of T-cell immunosuppression pre- and post-transplant.

Trust in Science as a Possible Mediator between Different Antecedents and COVID-19 Booster Vaccination Intention: An Integration of Health Belief Model (HBM) and Theory of Planned Behavior (TPB).

As the literature highlights, many health behavior theories try to explain both social and psychological variables influencing an individual's health behavior. This study integrates insights relative to the antecedents of getting vaccinated from health behavior theories, particularly including the health belief model (HBM), the theory of planned behavior (TPB), and the different socio-demographic factors. Furthermore, we considered the possible mechanism of impact of distrust in science on individuals' hesitance and resistance to taking up SARS-CoV-2 vaccination in subjects living in Italy.

APC transcription studies and molecular diagnosis of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene. Index patients with suspected FAP are usually investigated by APC coding region sequence and dosage analysis in a clinical diagnostic setting. The identification of an APC variant which is predicted to alter protein function enables predictive genetic testing to guide the management of family members.

SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation.

Background: SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC.

Severity of left ventricular dysfunction in heart failure patients affects the degree of serum-induced cardiomyocyte apoptosis. Importance of inflammatory response and metabolism.

Background/objectives: In heart failure pro-inflammatory cytokines contribute to cardiomyocytes loss by apoptosis and play a role in the remodelling of the extracellular matrix (ECM). Myocardial injury recruits endothelial progenitor cells (EPCs) to the site of damage and stimulates their differentiation, contributing to myocardial tissue repair. We investigated if the severity of left ventricular dysfunction in heart failure patients (HF) may influence the ability of serum to induce cardiomyocytes death and whether this effect is affected by inflammation and intracellular oxidative stress pathways.

Chemosensitivity of nonleukemic clonogenic precursors in AML patients in complete remission: association with CD34(+) mobilization and with disease-free survival.

A high number of CD34(+) cells in the peripheral blood during mobilization in patients with acute myeloid leukemia (AML) in complete remission (CR) is associated with a high relapse rate. The variability in chemoresistance of normal bone marrow precursors has been hypothesized as explanation for the variable CD34 mobilization in AML. In 37 patients with AML in CR, we determined the chemosensitivity of bone marrow clonogenic precursors to maphosphamide and etoposide, which was then correlated with the degree of CD34(+) mobilization.

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation.

Ninety-six AML patients in 1st CR were evaluated for peak CD34+ cell levels in peripheral blood (PB) during PBSC mobilization and harvest. Distribution of CD34+ cell peaks was determined and cases were grouped on the basis of 50th and 75th percentile: group A, those having a CD34+ cell peak ≤70 × 10(9)/L (n=48); group B, those having a CD34+ cell peak between 70 and 183 × 10(9)/L (n=24); group C, those having a CD34+ cell peak >183 × 10(9)/L (n=24). Irrespective of post-remission treatment received, group A had a disease free survival (DFS) of 73%, group B a DFS of 51% and group C of 30% (P=0.

Sildenafil reduces insulin-resistance in human endothelial cells.

Background: The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e.

Effects of a short-term exercise training on serum factors involved in ventricular remodelling in chronic heart failure patients.

Objectives: We studied the effect of a short-term (3 weeks) exercise training program on the number of circulating CD34/KDR(+) endothelial progenitor cells (EPCs) and on serum levels of matrix metalloproteinases (MMPs) in chronic heart failure (CHF) patients as well as on serum capacity to foster colony forming units-endothelial cells (CFU-ECs) in vitro.

Methods: Effectiveness of training was assessed by the 6-minute walking test (6MWT). Peripheral blood and serum were obtained from fourteen patients with CHF due to coronary artery disease before and after an inpatient aerobic exercise training program.

Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes.

We analyzed, by the latest high-resolution SNP arrays, 19 Normal Karyotype (NK)-AML patients at diagnosis (Dx) and remission (R) phases, to determine the number of tumor-associated copy number abnormalities (CNAs) and copy neutral-loss of heterozygosity (CN-LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor-associated CNAs was determined after comparison of matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient).

Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML.

By conventional metaphase and SNP array cytogenetics we serially studied a patient affected by high-risk myelodysplastic syndrome (MDS), documenting the conversion from partial trisomy 8q to trisomy 8 and partial tetrasomy 8q during progression to acute myeloid leukemia (AML). Moreover, the serial application of high resolution genomic array analysis at different disease stages allowed the description of cryptic abnormalities and the demonstration of their enrichment in the AML phase. In particular the detection and quantification of a copy-neutral loss of heterozygosity region located in chromosome 11q guided the search for point mutations in the CBL gene, thus allowing the escription of the novel missense mutation K382E and the demonstration of its selection during progression to secondary AML.

Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy.

Background: According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML) patients in apparent complete remission (CR) after chemotherapy induction may be classified into three groups: (i) normally responsive; (ii) chemoresistant; (iii) highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD) and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM) in these phenotypic features.

Influence of complex variant chromosomal translocations in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

Unlabelled: Cytogenetic variants of the Philadelphia (Ph) chromosome can be observed in 5-8% of patients diagnosed with Chronic Myelogenous Leukemia (CML), and usually involve at least one chromosome other than 9 and 22. Despite the genetically heterogeneous nature of these alterations, available data indicate that CML patients displaying complex variant translocations (CVTs) do not exhibit a less favorable outcome as compared to individuals presenting conventional Ph-positive CML.

Patients And Methods: We report our experience with 10 CML patients carrying CVTs among 153 newly diagnosed cases followed at our Institution.

Salt intake induces epithelial-to-mesenchymal transition of the peritoneal membrane in rats.

Background: Dietary salt intake has been linked to hypertension and cardiovascular disease through volume-mediated effects. Accumulating evidence points to direct negative influence of salt intake independent of volume overload, such as cardiac and renal fibrosis, mediated through transforming growth factor beta (TGF-beta). Epithelial-to-mesenchymal transition (EMT) has been implicated as a key process in chronic fibrotic diseases, such as chronic kidney disease or heart failure.

Peripheral blood mononuclear cells from mild cognitive impairment patients show deregulation of Bax and Sod1 mRNAs.

Elevated oxidative stress-induced apoptosis has been found in peripheral cells from patients with Alzheimer's disease (AD). Furthermore, treatment of lymphocytes from AD patients, with Abeta(1-42) and H(2)O(2) results in enhanced apoptosis. Mild cognitive impairment (MCI), a clinical condition between normal aging and AD, shares with AD a similar pattern of peripheral markers of oxidative stress.

An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.

Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (<20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 (14 familial and 7 sporadic cases) who were all found to have the same c.

Gonosomal mosaicism for a nonsense mutation (R1947X) in the NF1 gene in segmental neurofibromatosis type 1.

Segmental neurofibromatosis type 1 (SNF1), characterized by the regionally limited distribution of neurofibromatosis type 1 (NF1) features, has been attributed to mosaicism for an NF1 gene mutation. The occurrence of classical NF1 in the offspring of a parent with SNF1 suggests that cutaneous mosaicism may be accompanied by gonadal mosaicism. We studied a girl with generalized NF1, and her mother who has SNF1.

Survivin expression in chronic myeloid leukemia.

In this study, we investigated the expression of survivin (SVV) in 44 patients with typical Ph-positive chronic myeloid leukemia (CML) in different phases of the disease as well as in 20 matched healthy donors. We found a very high SVV expression in a predominant percentage of CML patients. We also observed a significantly increased SVV expression in patients in accelerated/blastic phase of the disease compared to patients in chronic phase.