Machine Perfusions in Liver Transplantation: The Evidence-Based Position Paper of the Italian Society of Organ and Tissue Transplantation.

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d'Organo (SITO) promoted the development of an evidence-based position paper.

A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1 in a Von Hippel-Lindau Renal Oncocytoma.

The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1 chronic stabilization. By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by -ketoglutarate accumulation following Krebs cycle slowdown. Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma.

Dacron Conduit for Extracardiac Total Cavopulmonary Anastomosis: A Word of Caution.

Background: The extracardiac conduit technique is a valid option for completing total cavopulmonary anastomosis (TCPC) in patients with a single ventricle. The technique allows for beating heart surgery, optimal flow dynamics, and reduced postoperative atrial arrhythmia. Different types of conduit have been proposed.

Chibby 1: a new component of β-catenin-signaling in chronic myeloid leukemia.

Chibby 1 (CBY1) is a small and evolutionarily conserved protein, which act as β-catenin antagonist. CBY1 is encoded by (22q13.1) Its antagonistic function on β-catenin involves the direct interaction with: The C-terminal activation domain of β-catenin, which hinders β-catenin binding with Tcf/Lef transcription factors hence repressing β-catenin transcriptional activation.

Mitochondrial DNA sequencing demonstrates clonality of peritoneal implants of borderline ovarian tumors.

Borderline ovarian tumors are rare low malignant potential neoplasms characterized by the absence of stromal invasion, whose main prognostic factors are stage and type of peritoneal implants. The latter are defined as invasive when cell proliferation invades the underlying tissue (peritoneal surface, omentum and intestinal wall), or noninvasive. It is still unknown if these implants are metastatic spread from the primary ovarian mass or a neoplastic transformation de novo of the peritoneal surface.

Positive selection of lactase persistence among people of Southern Arabia.

Objective: Frequency patterns of the lactase persistence (LP)-associated -13,915 G allele and archaeological records pointing to substantial role played by southern regions in the peopling and domestication processes that involved the Arabian Peninsula suggest that Southern Arabia plausibly represented the center of diffusion of such adaptive variant. Nevertheless, a well-defined scenario for evolution of Arabian LP is still to be elucidated and the burgeoning archaeological picture of complex human migrations occurred through the peninsula is not matched by an equivalent high-resolution description of genetic variation underlying this adaptive trait. To fill this gap, we investigated diversity at a wide genomic interval surrounding the LCT gene in different Southern Arabian populations.

Cytological features of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" and their correlation with tumor histology.

Among thyroid papillary carcinomas (PTCs), the follicular variant is the most common and includes encapsulated forms (EFVPTCs). Noninvasive EFVPTCs have very low risk of recurrence or other adverse events and have been recently proposed to be designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features or NIFTP, thus eliminating the term carcinoma. This proposal is expected to significantly impact the risk of malignancy associated with the currently used diagnostic categories of thyroid cytology.

A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest.

Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliable pool of candidate variants for further investigations. The prioritization workflow relies on an exhaustive functional annotation through the mtDNA extraction pipeline MToolBox and includes Macro Haplogroup Consensus Sequences to filter out fixed evolutionary variants and report rare or private variants, the nucleotide variability as reported in HmtDB and the disease score based on several predictors of pathogenicity for non-synonymous variants.

14-3-3 Binding and Sumoylation Concur to the Down-Modulation of β-catenin Antagonist chibby 1 in Chronic Myeloid Leukemia.

The down-modulation of the β-catenin antagonist Chibby 1 (CBY1) associated with the BCR-ABL1 fusion gene of chronic myeloid leukemia (CML) contributes to the aberrant activation of β-catenin, particularly in leukemic stem cells (LSC) resistant to tyrosine kinase (TK) inhibitors. It is, at least partly, driven by transcriptional events and gene promoter hyper-methylation. Here we demonstrate that it also arises from reduced protein stability upon binding to 14-3-3σ adapter protein.

Early and mid-term clinical experience with extracellular matrix scaffold for congenital cardiac and vascular reconstructive surgery: a multicentric Italian study.

Objectives: The aim of this multicentric study was to outline surgical indications and evaluate mid-term outcomes of porcine extracellular matrix (ECM) in surgery for congenital heart disease (CHD).

Methods: The use of ECM was categorized into four major groups: A, valve repair; B, septal reconstruction; C, arterial plasty; D, other use. Primary endpoints of analysis were reintervention (either surgical or interventional) when related to ECM, and functional ECM failure.

DNA methyltransferase 1 drives transcriptional down-modulation of β catenin antagonist Chibby1 associated with the BCR-ABL1 gene of chronic myeloid leukemia.

The decrease of Chibby1 (CBY1) contributes to β catenin constitutive activation associated with the presence of the BCR-ABL1 fusion gene of chronic myeloid leukemia (CML). This is mediated by transcriptional events and driven by DNA hyper-methylation at promoter-associated CpG islands of the CBY1-encoding gene C22orf2. Moreover, CBY1 transcriptional induction proceeding from promoter de-methylation is a component of BCR-ABL1+ cell response to Imatinib (IM).

BCR-ABL1-associated reduction of beta catenin antagonist Chibby1 in chronic myeloid leukemia.

Beta Catenin signaling is critical for the self-renewal of leukemic stem cells in chronic myeloid leukemia. It is driven by multiple events, enhancing beta catenin stability and promoting its transcriptional co-activating function. We investigated the impact of BCR-ABL1 on Chibby1, a beta catenin antagonist involved in cell differentiation and transformation.

Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL fusion protein. However, the phenotype of leukemic stem cells (LSC) is sustained by β catenin rather than by the BCR-ABL TK. β catenin activity in CML is contingent upon its stabilization proceeding from the BCR-ABL-induced phosphorylation at critical residues for interaction with the Adenomatous polyposis coli (APC)/Axin/glycogen synthase kinase 3 (GSK3) destruction complex or GSK3 inactivating mutations.

Relevance of mitochondrial genetics and metabolism in cancer development.

Cancer cells are characterized in general by a decrease of mitochondrial respiration and oxidative phosphorylation, together with a strong enhancement of glycolysis, the so-called Warburg effect. The decrease of mitochondrial activity in cancer cells may have multiple reasons, related either to the input of reducing equivalents to the electron transfer chain or to direct alterations of the mitochondrial respiratory complexes. In some cases, the depression of respiratory activity is clearly the consequence of disruptive mitochondrial DNA (mtDNA) mutations and leads as a consequence to enhanced generation of reactive oxygen species (ROS).

Left main coronary artery stenosis secondary to severe pulmonary artery dilation.

A 45-year-old lady with dyspnea and occasional precordial chest pain was diagnosed with a huge sinus venosus atrial septal defect and partial anomalous pulmonary venous return. Preoperative coronary angiography disclosed severe main stem stenosis, considered secondary to compression by the dilated pulmonary trunk. Atrial septal defect closure and pulmonary artery reduction plasty were performed.

Gadd45a transcriptional induction elicited by the Aurora kinase inhibitor MK-0457 in Bcr-Abl-expressing cells is driven by Oct-1 transcription factor.

The advantage of Aurora kinase (AK) inhibitors in chronic myeloid leukemia (CML) therapy mostly arises from "off-target" effects on tyrosine kinase (TK) activity of wild type (wt) or mutated Bcr-Abl proteins which drive the disease resistance to imatinib (IM). We proved that the AK inhibitor MK-0457 induces the growth arrest DNA damage-inducible (Gadd) 45a through recruitment of octamer-binding (Oct)-1 transcription factor at a critical promoter region for gene transcription and covalent modifications of histone H3 (lysine 14 acetylation, lysine 9 de-methylation). Such epigenetic chromatin modifications may depict a general mechanism promoting the re-activation of tumor suppressor genes silenced by Bcr-Abl.

Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in chronic myeloid leukemia.

The loss-of-function of ten-eleven-translocation (TET) 2, a Fe(2+) -oxoglutarate-dependent dioxygenase catalyzing 5 methyl cytosine (5mC) conversion into 5-hydroxymethylcytosine (5hmC), contributes to the hematopoietic transformation in vivo. The aim of our study was to elucidate its role in the phenotype of chronic myeloid leukemia (CML), a myeloproliferative disease caused by the Bcr-Abl rearranged gene. We first confirmed TET2 interaction with the Bcr-Abl protein predicted by a Fourier-based bioinformatic method.

Rasmussen's aneurysm in childhood: a case report.

In medical literature, few cases of Rasmussen's aneurysm have been reported until now, and to the best of our knowledge, there has been no description of a case of Rasmussen's aneurysm in childhood. The child described in the case report had a restrictive cardiomyopathy, complicated by pulmonary hypertension, in association with miliary tuberculosis.