Hypermethylation-Mediated Silencing of , and Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies.

Gene expression is controlled by epigenetic deregulation, a hallmark of cancer. The DNA methylome of canine diffuse large B-cell lymphoma (cDLBCL), the most frequent malignancy of B-lymphocytes in dog, has recently been investigated, suggesting that aberrant hypermethylation of CpG loci is associated with gene silencing. Here, we used a multi-omics approach (DNA methylome, transcriptome and copy number variations) combined with functional in vitro assays, to identify putative tumour suppressor genes subjected to DNA methylation in cDLBCL.

Development and Validation of the Acute PNeumonia Early Assessment Score for Safely Discharging Low-Risk SARS-CoV-2-Infected Patients from the Emergency Department.

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed ( = 128) and validated ( = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital ( = 97). The score's performance was compared to that of the National Early Warning Score 2 (NEWS2).

G-Quadruplex Modulation of SP1 Functional Binding Sites at the Proximal Promoter.

The regulation of conformational arrangements of gene promoters is a physiological mechanism that has been associated with the fine control of gene expression. Indeed, it can drive the time and the location for the selective recruitment of proteins of the transcriptional machinery. Here, we address this issue at the proximal promoter where three G-quadruplex forming sites are present (kit1, kit2 and kit*).

DNA elements for constitutive androstane receptor- and pregnane X receptor-mediated regulation of bovine CYP3A28 gene.

The regulation of cytochrome P450 3A (CYP3A) enzymes is established in humans, but molecular mechanisms of its basal and xenobiotic-mediated regulation in cattle are still unknown. Here, ~10 kbp of the bovine CYP3A28 gene promoter were cloned and sequenced, and putative transcription factor binding sites were predicted. The CYP3A28 proximal promoter (PP; -284/+71 bp) contained DNA elements conserved among species.

Validation of epigenetic mechanisms regulating gene expression in canine B-cell lymphoma: An in vitro and in vivo approach.

Despite canine B-cell Lymphoma (BCL) representing the most common haematological tumour, epigenetic events driving development and progression are scarcely known. Recently, canine Diffuse Large BCL (DLBCL) DNA methylome by genome-wide CpG microarray has identified genes and pathways associated to pathogenesis. To validate data previously obtained by array analysis, the CLBL-1 cell line was used and the HOXD10, FGFR2, ITIH5 and RASAL3 genes were selected.

Epidemiology of amyotrophic lateral sclerosis in Friuli-Venezia Giulia, North-Eastern Italy, 2002-2014: a retrospective population-based study.

Objectives: To describe the epidemiology of Amyotrophic Lateral Sclerosis (ALS) in Friuli-Venezia Giulia (FVG) region, Italy, over a 13-year period (2002-2014), estimating ALS (a) incidence, prevalence, and clinical features; (b) mortality, also comparing Udine municipality to the rest of FVG.

Methods: We conducted a retrospective population-based study. ALS incident cases were ascertained using multiple sources and validated through expert review.

Targeting Canine Promoter by Candidate DNA G-Quadruplex Ligands.

G-quadruplexes (G4) are nucleic acid secondary structures frequently assumed by G-rich sequences located mostly at telomeres and proto-oncogenes promoters. Recently, we identified, in canine (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) promoter, two G-rich sequences able to fold into G4: d_kit1 and d_kit2_A16. In this study, an anthraquinone (AQ1) and an anthracene derivative (AN6), known to stabilize the G4 structures of the corresponding human h_kit1 and h_kit2, were tested on the canine G4 and in two canine mast cell tumor (MCT) cell lines (C2 and NI-1) to verify their capability to down-regulate expression.

Identification of Piperidinyl-amine Derivatives as Novel Dual Binders of Oncogene c-myc/c-Kit G-quadruplexes.

In the last years, it has been shown that the DNA secondary structure known as G-quadruplex is also involved in the regulation of oncogenes transcription, such as , , , , , and . DNA G-quadruplexes, formed in the promoter region of these proto-oncogenes, are considered alternative anticancer targets since their stabilization causes a reduction of the related oncoprotein overexpression. In this study, a structure-based virtual screening toward the experimental DNA G-quadruplex structures of and was performed by using Glide for the docking analysis of a commercial library of approximately 693 000 compounds.

DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma.

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls.

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models.

Stabilization of G-quadruplex (G4) structures in promoters is a novel promising strategy to regulate gene expression at transcriptional and translational levels. c-KIT proto-oncogene encodes for a tyrosine kinase receptor. It is involved in several physiological processes, but it is also dysregulated in many diseases, including cancer.

Peritoneal resting with heparinized lavage reverses peritoneal type I membrane failure. A comparative study of the resting effects on normal membranes.

Background: Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral.

Sequencing and G-quadruplex folding of the canine proto-oncogene KIT promoter region: might dog be used as a model for human disease?

Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2) were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation.

Increased risk of fatal infections in women starting peritoneal dialysis.

Background And Objectives: Although cardiovascular disease (CVD) is an important cause of morbidity and mortality in patients with end-stage renal disease, non-CVD causes account for more than 50% of total deaths. We previously showed that, compared with men, women starting dialysis-- both hemodialysis and peritoneal dialysis (PD)--have higher non-CVD mortality rates. Here, we evaluate sex-specific outcomes in a large cohort of incident PD patients.

Pretransplant peritoneal dialysis relative to hemodialysis improves long-term survival of kidney transplant patients: a single-center observational study.

Background: Kidney transplantation is the best option for the treatment of end-stage renal disease in terms of survival and quality of life. These results can be influenced by the pretransplant dialysis modality. The aim of this study was to evaluate whether the pretransplantation dialysis modality influences patient and allograft survival beyond 10 years and examine the potential risk factors associated with the outcomes.

Endocrine alterations and cardiovascular risk in CKD: is there a link?

The kidney plays an important role in synthesis, metabolism and elimination of a plethora of hormones. Thus, chronic kidney disease (CKD) naturally progresses with hormonal disorders. This review will focus in emerging evidence regarding the association between CKD-associated disturbances in the hypothalamic-pituitary-gonadal axis and cardiovascular risk factors.

Atrial fibrillation and right bundle branch block complicating coil embolization of a huge pulmonary arterio-venous malformation.

Coil embolization is a safe therapy for pulmonary arterio-venous malformations (PAVMs). We report the case of a 72-year-old woman affected by hereditary hemorrhagic teleangectasia who experienced right bundle branch block and atrial fibrillation 36 hours after embolization of an extended PAVM. To our knowledge, this is the first case of such a complication of embolization of a pulmonary fistula, presumably due to an acute pressure overload on both the right atrium and ventricle.

Outcome and prognostic factors in HIV-1-infected patients on dialysis in the cART era: a GESIDA/SEN cohort study.

Background: Prognosis of HIV-infected patients on dialysis has improved. Few studies have compared survival between HIV-infected and HIV-negative patients on dialysis in the combined antiretroviral therapy (cART) era. We compared the outcome of HIV-infected patients on dialysis with a matched HIV-negative cohort.

Cystatin C as marker of residual renal function in patients on peritoneal dialysis: relation with parameters of peritoneal function.

Introduction: Cystatin C (CysC) is a nonglycosylated protein of low molecular weight not influenced by age, sex or inflammation. The aim of this paper is to ascertain the usefulness of serum CysC level determination in peritoneal dialysis (PD) patients.

Material And Methods: CysC serum levels were determined in 80 PD patients.

Inherent high peritoneal transport and ultrafiltration deficiency: their mid-term clinical relevance.

Background: High peritoneal transport has been associated with poorer outcome in peritoneal dialysis (PD) patients, but not necessarily because of PD-dependent conditions. Our primary objective was to analyse the influences of baseline peritoneal small solute transport and ultrafiltration (UF) capacity on patient and technique survival, after adjusting for comorbid conditions. A secondary objective was to determine whether high transport was associated with basal comorbidity.

Peritoneal transport in peritoneal dialysis patients is not affected by transitorily successful renal transplantation.

Patients returning to peritoneal dialysis (PD) from failed renal transplantation are recognized to be inflamed, and this situation might produce a high peritoneal solute transport status. We wanted to determine if a period of time with a kidney allograft induces a change in peritoneal function. We studied 19 PD patients who had been living with a graft for a mean of 47 +/- 39 months.

[Renal transplantation in patients with HIV infection].

The prevalence of human immunodeficience virus (HIV) infection among patients under renal replacement therapy varies, with estimates of 1% for Europe and 1.5% for the United States. Survival in HIV infected individuals receiving renal replacement therapy has improved since the introduction of high activity antiretroviral therapy (HAART).

Treatment of anorexia and malnutrition in peritoneal dialysis patients with megestrol acetate.

Anorexia and malnutrition are common complications and powerful predictors of morbidity and mortality in peritoneal dialysis (PD) patients. Megestrol acetate (MA) is a progestogen that has been demonstrated to increase appetite and weight in patients with cancer or acquired immunodeficiency syndrome. To determine whether MA might benefit PD patients, we treated 32 patients with 160 mg MA daily.