The c.4096+1G>A Is a Founder Variant Which Originated in Ancient Times.

Approximately 30-50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the (OMIM 113705) and (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response. Women who carry pathogenic variants are particularly likely to develop breast cancer (BC) and ovarian cancer (OC), with a 45-79 percent and 39-48 percent chance, respectively. The c.

Distractions in the operating room: a survey of the healthcare team.

Background: Distractions during surgical procedures are associated with team inefficiency and medical error. Little is published about the healthcare provider's perception of distraction and its adverse impact in the operating room. We aim to explore the perception of the operating room team on multiple distractions during surgical procedures.

Validation and Data-Integration of Yeast-Based Assays for Functional Classification of BRCA1 Missense Variants.

Germline mutations in the BRCA1 gene have been reported to increase the lifetime risk of developing breast and/or ovarian cancer (BOC). By new sequencing technologies, numerous variants of uncertain significance (VUS) are identified. It is mandatory to develop new tools to evaluate their functional impact and pathogenicity.

STAT3 induces breast cancer growth via ANGPTL4, MMP13 and STC1 secretion by cancer associated fibroblasts.

In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6, act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins.

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions.

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (, , , , , , , , , , , ) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, for germline mutation in genes. The analysis was extended to 5'UTR and 3'UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients.

Atraumatic Restorative Treatment-Sealed versus Nonsealed First Permanent Molars: A 3-Year Split-Mouth Clinical Trial.

To investigate the efficacy of atraumatic restorative treatment (ART) sealants vs. no sealant in preventing the development of dentine caries lesions in first permanent molars over a period of 3 years. A total of 187 schoolchildren (aged 6-8 years) from a low-income population presenting the 4 first permanent molars without clinically detectable dentine caries lesions were selected to be part of a split-mouth clinical trial.

Liver-Specific siRNA-Mediated Stat3 or C3 Knockdown Improves the Outcome of Experimental Autoimmune Myocarditis.

Myocarditis can lead to autoimmune disease, dilated cardiomyopathy, and heart failure, which is modeled in the mouse by cardiac myosin immunization (experimental autoimmune myocarditis [EAM]). Signal transducer and activator of transcription 3 (STAT3) systemic inhibition exerts both preventive and therapeutic effects in EAM, and STAT3 constitutive activation elicits immune-mediated myocarditis dependent on complement C3 and correlating with activation of the STAT3-interleukin 6 (IL-6) axis in the liver. Thus, liver-specific STAT3 inhibition may represent a therapeutic option, allowing to bypass the heart toxicity, predicted by systemic STAT3 inhibition.

Bailout Implantation of a New Single-Branch Stent Graft for the Aortic Arch.

In this paper we describe a case of a rapidly growing pseudoaneurysm of the aortic arch occurring after surgery for acute type A aortic dissection that was successfully treated with an off-the-shelf, single-branch, dual-module aortic arch endovascular stent graft. The main module, which has a side-branch for the innominate artery, was implanted in the aortic arch and in the descending thoracic aorta. The second module was deployed in the ascending aorta and connected to the main module through a proprietary interlocking system.

Effect of GLP-1 and GIP on C-peptide secretion after glucagon or mixed meal tests: Significance in assessing B-cell function in diabetes.

Background: The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT).

Methods: We conducted GST and MMTT in 10 healthy people (aged 25-40 years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1 mg i.v.

A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes.

Aims: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients. Similarly to metformin, D-chiro-inositol (DCI), as putative mediator of intracellular insulin action, can act as insulin sensitizer. The aim of this pilot study was to evaluate the hypothesis that DCI plus folic acid may improve glucose control reducing insulin resistance in overweight or obese T1D patients.

ART is an alternative for restoring occlusoproximal cavities in primary teeth - evidence from an updated systematic review and meta-analysis.

Background: A previous systematic review showed that atraumatic restorative treatment (ART) can be an option to restore the occlusoproximal cavities in primary teeth; however, few studies fulfilled the criteria of inclusion to generate a high level of evidence.

Aim: To update the existing systematic review and address questions regarding survival rate of ART restorations compared to the conventional approach in occlusoproximal cavities in primary molars.

Design: The search was extended beyond the original search through the PubMed/MEDLINE database up to February 2016.

Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus.

Introduction: Type 1 diabetes (T1DM) is an immune-mediated disease induced by antigen-specific T cells infiltrating pancreatic beta cells leading to the progressive loss of endogenous insulin secretion.

Areas Covered: The identification of specific components of the autoimmune response favoured the implementation of several immunomodulatory therapies including antiCD3 monoclonal antibody (mAb) called otelixizumab. Otelixizumab is a chimeric monoclonal antibody that targets the ε-chain of the CD3T-lymphocyte surface receptor that has been developed with the aim of short therapeutic courses capable of inducing a remission of T1DM.

Coronary Artery Bypass Grafting in Elderly Patients: Insights from a Comparative Analysis of Total Arterial and Conventional Revascularization.

The benefits of total arterial (TAR) versus conventional (CR) revascularization are controversial in the higher-risk cohort of elderly patients. Taking for granted its benefit on long-term survival, we evaluated the effect of TAR on safety (death, myocardial infarction, and stroke) of patients undergoing CABG. Between 2000 and 2009, 487 patients >75 years underwent isolated CABG at our institution (150 TAR and 337 CR).

Survival Rate of Atraumatic Restorative Treatment (ART) Restorations Using a Glass Ionomer Bilayer Technique with a Nanofilled Coating: A Bi-center Randomized Clinical Trial.

Purpose: The high-viscosity consistency of glass ionomer cement (GIC) contributes to its inappropriate adaptation, while the material's premature exposure to humidity decreases its mechanical properties. This study's purposes were to: (1) investigate approximal atraumatic restorative treatment (ART) restorations' survival in primary molars using two different insertion techniques and two surface protection materials; and (2) compare the results of cities where treatments were performed.

Methods: A total of 389 six- to seven-year-olds were selected from two cities in Brazil and randomly assigned into four groups: (1) ART restorations plus petroleum jelly (PJ); (2) bilayer-ART restorations plus PJ; (3) ART restorations plus nanofilled coating for GIC (NC); (4) bilayer-ART restorations plus NC.

Comparison of Efficacy and Cost of Iodine Impregnated Drape vs. Standard Drape in Cardiac Surgery: Study in 5100 Patients.

We sought to examine the efficacy in preventing surgical site infection (SSI) in cardiac surgery, using two different incise drapes (not iodine-impregnated and iodine-impregnated). A cost analysis was also considered. Between January 2008 and March 2015, 5100 consecutive cardiac surgery patients, who underwent surgery in our Institute, were prospectively collected.

Bilayer technique and nano-filled coating increase success of approximal ART restorations: a randomized clinical trial.

Background: The high-viscosity consistency of glass ionomer cement (GIC) may lead to its incorrect adaptation into the cavity and therefore to restoration failure.

Aim: To compare two different insertion techniques for GIC in approximal atraumatic restorative treatment (ART) restorations and two different surface protection materials.

Design: Approximal caries lesion in primary molars from 208 schoolchildren was randomly assigned into four groups: G1, conventional GIC insertion protected with petroleum jelly (PJ); G2, bilayer technique protected with PJ; G3 conventional GIC insertion protected with nano-filled particles coating for GIC (NPC); G4, bilayer technique protected with NPC.

Low-cost glass ionomer cement as ART sealant in permanent molars: a randomized clinical trial.

Clinical trials are normally performed with well-known brands of glass ionomer cement (GIC), but the cost of these materials is high for public healthcare in less-affluent communities. Given the need to research cheaper materials, it seems pertinent to investigate the retention rate of a low-cost GIC applied as atraumatic restorative treatment (ART) sealants in two centers in Brazil. Four hundred and thirty-seven 6-to-8-year-old schoolchildren were selected in two cities in Brazil.

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD.

Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control.

Aims: Experimental data demonstrated that gastrin has incretin-like stimulating actions on β-cells, resulting in a promotion of glucose-induced insulin secretion. As proton pump inhibitors (PPIs) consistently increase plasma gastrin levels, a possible effect of this treatment on glucose-insulin homeostasis may be hypothesized. Therefore, the aim of this study was to evaluate the effect of chronic PPIs treatment on glycemic control in patients affected by type 2 diabetes.

Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: a study by the Chronic Malignancies Working Party of the EBMT.

Patients with chronic myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation may be treated by tyrosine kinase inhibitors and/or by donor lymphocyte infusions. The best strategies and timing of administration of lymphocytes are unclear. We analyzed 155 patients who relapsed after allogeneic stem cell transplantation with disease detectable only by molecular methods and who subsequently received lymphocytes.