Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway

we read with great interest the paper by Dr. Chen et al1, recently published in European Review for Medical and Pharmacological Sciences and titled ‘‘Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway’’. Authors concluded that lncRNA00673 is highly expressed and may be a potential target for the treatment of Hepatocellular Carcinoma (HCC). Moreover, according to authors, it can promote the proliferation and metastasis of HCC by the regulation of Notch signaling pathway. We congratulate the authors for their interesting work

Capability of non liner eddy viscosity model in predicting complex flows

Paper presented at the 6th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, South Africa, 30 June - 2 July, 2008.The research field of the study is related with turbulence modeling. The general objective is the implementation in a commercial code, of two equations Non Linear Eddy Viscosity Model (NLEVM) which removes Boussinesq linear approximation for the Reynolds stress tensor. The work described in the paper implements a second order k-ε model based over Shih, Zhu and Lumley (1993) [1] and Craft, Launder and Suga (1996) [2] in the finite volume commercial code ANSYS-FLUENT v. 6.3.26, by writing additional subroutines. The model has been validated through experimental and DNS data available in the literature. The benchmarks shown in this paper are the straight Square Duct [8] and the Backward-Facing Step [9, 10]. After the validation, the model has been used for predicting the flow behavior for complex industrial applications. The geometry used is similar to the bowl-shape downcomer of nuclear reactor. This is an application field of interest still under study by the same research group and an international consortium.vk201

Laparoscopic Excision of Endometriosis May Require Unilateral Parametrectomy

Nerve-sparing complete excision of endometriosis may not be possible. In these patients, unilateral parametrectomy may be a reasonable alternative management strategy

The Borexino Thermal Monitoring & Management System and simulations of the fluid-dynamics of the Borexino detector under asymmetrical, changing boundary conditions

A comprehensive monitoring system for the thermal environment inside the Borexino neutrino detector was developed and installed in order to reduce uncertainties in determining temperatures throughout the detector. A complementary thermal management system limits undesirable thermal couplings between the environment and Borexino's active sections. This strategy is bringing improved radioactive background conditions to the region of interest for the physics signal thanks to reduced fluid mixing induced in the liquid scintillator. Although fluid-dynamical equilibrium has not yet been fully reached, and thermal fine-tuning is possible, the system has proven extremely effective at stabilizing the detector's thermal conditions while offering precise insights into its mechanisms of internal thermal transport. Furthermore, a Computational Fluid-Dynamics analysis has been performed, based on the empirical measurements provided by the thermal monitoring system, and providing information into present and future thermal trends. A two-dimensional modeling approach was implemented in order to achieve a proper understanding of the thermal and fluid-dynamics in Borexino. It was optimized for different regions and periods of interest, focusing on the most critical effects that were identified as influencing background concentrations. Literature experimental case studies were reproduced to benchmark the method and settings, and a Borexino-specific benchmark was implemented in order to validate the modeling approach for thermal transport. Finally, fully-convective models were applied to understand general and specific fluid motions impacting the detector's Active Volume.Comment: arXiv admin note: substantial text overlap with arXiv:1705.09078, arXiv:1705.0965

A Reappraisal of Lymphadenectomy in Common Gynecological Cancers

Objectives: Lymph node dissection (LND) in gynecological malignancies has always been a cornerstone in the diagnosis of metastasis, it is also considered an important prognostic factor, and a reliable guide to management strategies. However, its incidence of complications, namely lymphedema, vascular injuries and other lesions, has led to a reconsideration of its efficacy and a comparison of the role of systematic vs. sentinel lymph node (SLN) dissection. Mechanism: Review of the literature using keywords such as “lymph nodes”, “sentinel lymph nodes”, “morbidity and mortality”, “gynecological cancers”, “endometrial cancer”, “ovarian cancer”, and “cervical cancer”. Findings in Brief: In the case of endometrial cancer, several studies have investigated the efficacy of SLN compared with systematic LND. Most of the results demonstrated the efficacy of SLN dissection in endometrial cancer, with the added benefit of lower morbidity. In patients with ovarian cancer, the mainstay of treatment is debulking with optimal cytoreductive surgery. Recent studies have compared systematic lymphadenectomy to non-lymphadenectomy, with an additional advantage in the cases of lymphadenectomy. However, since its publication, the lymphadenectomy in ovarian cancers (LIONS) trial, has revolutionized the standard of care for patients with advanced ovarian cancer and has called into question the increased morbidity and mortality in systematic lymphadenectomy. In cervical cancers, lymph node status is considered to be the most important prognostic factor. In this case, limiting lymphadenectomy to the borders of the inferior mesenteric artery seems promising, and studies are currently being carried out to investigate the feasibility of SLN dissection instead of systematic lymph node dissection. Conclusions: SLN dissection is associated with lower morbidity and mortality, and has been shown to be superior to systematic lymphadenectomy in several studies. However, more research and specific guidelines are needed to better select either one or the other method in the management of gynecological cancers. Copyright: © 2023 The Author(s)

Current preventive policies and practices against Vaccine-Preventable Diseases and tuberculosis targeted for workers from hospitals of the Sardinia Region, Italy

Introduction. Health care Workers are exposed to infectious diseases more than the general population. Many of these infections are preventable by vaccination. The objective in this study is to investigate whether, how, and which vaccination underwent Sardinia Health Care Workers (HCWs) and the variability of policies in different Hospital Health Managements of the whole region. Methods. In March 2013, we enrolled the Hospital Health Management of all the 32 Sardinia hospitals. We investigate on immunity against vaccine-preventable diseases and education campaigns about recommended vaccinations for HCWs. Flu, hepatitis B, measles-mumps-rubella, varicella and tuberculosis were the objects of our research. Results. In most of the hospitals, influenza vaccination coverage among HCWs is less than 6%. Hepatitis B antibody assay was performed in all the respondent hospitals but only 14 had available data as collected electronically. Most of the hospitals did not perform serological tests for the evaluation of antibodies against Varicella, Measles, Mumps and Rubella in their HCWs. In 30 hospitals Mantoux test was replaced or integrated by "in vitro" test for health surveillance protocols. Conclusions. This method produced a large amount of data in small time and at a low cost. Sending back data to respective Hospital Health Management (HHM) we took a step towards greater awareness of the issue of biological risks of HCWs and of vaccine coverage

The EcoThermo project: key and innovative aspects

In this paper we present the most innovative aspects of the EC-FP7 EcoThermo project. The main aim of the project consists on innovating the technique of heat cost allocation in buildings with a centralized heating system, overcoming the heat cost allocator drawbacks for reliability, measurement reproducibility and traceability and contexts of applications. Given the complexity of the project, we will focus on its main aspects, such as the use of a virtual sensor to estimate the radiators heating power, the design of electronic valves fitted out with an energy harvesting system and the original wireless communication protocol

The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans

The dopamine D2 and D3 receptors are implicated in schizophrenia and its pharmacological treatments. These receptors undergo intracellular trafficking processes that are modulated by dysbindin-1 (Dys). Indeed, Dys variants alter cognitive responses to antipsychotic drugs through D2-mediated mechanisms. However, the mechanism by which Dys might selectively interfere with the D3 receptor subtype is unknown. Here, we revealed an interaction between functional genetic variants altering Dys and D3. Specifically, both in patients with schizophrenia and in genetically modified mice, concomitant reduction in D3 and Dys functionality was associated with improved executive and working memory abilities. This D3/Dys interaction produced a D2/D3 imbalance favoring increased D2 signaling in the prefrontal cortex (PFC) but not in the striatum. No epistatic effects on the clinical positive and negative syndrome scale (PANSS) scores were evident, while only marginal effects on sensorimotor gating, locomotor functions, and social behavior were observed in mice. This genetic interaction between D3 and Dys suggests the D2/D3 imbalance in the PFC as a target for patient stratification and procognitive treatments in schizophrenia

IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma (MM) and mantle-cell lymphoma (MCL). However, patients continuously relapse or are intrinsically resistant to this class of drugs. Here, to identify targets that synergize with PIs, we carried out a functional screening in MM cell lines using a short hairpin RNA library against cancer driver genes. Isocitrate dehydrogenase 2 (IDH2) was identified as a top candidate, showing a synthetic lethal activity with the PI carfilzomib (CFZ). Combinations of FDA approved PIs with a pharmacological IDH2 inhibitor (AGI-6780) triggered synergistic cytotoxicity in MM, MCL, and Burkitt's lymphoma (BL) cell lines. CFZ/AGI-6780 treatment increased death of primary CD138+ cells from MM patients and exhibited a favorable cytotoxicity profile towards peripheral blood mononuclear cells and bone marrow-derived stromal cells. Mechanistically, CFZ/AGI-6780 combination significantly decreased tricarboxylic acid (TCA) cycle activity and ATP levels, as a consequence of enhanced IDH2 enzymatic inhibition. Specifically, CFZ treatment reduced the expression of nicotinamide phosphoribosyltransferase (NAMPT), thus limiting IDH2 activation through the NAD+-dependent deacetylase SIRT3. Consistently, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM cell death. Finally, inducible IDH2 knockdown enhanced the therapeutic efficacy of CFZ in a subcutaneous xenograft model of MM, resulting in inhibition of tumor progression and extended survival. Taken together, these findings indicate that NAMPT/SIRT3/IDH2 pathway inhibition enhances the therapeutic efficacy of PIs, thus providing compelling evidence for treatments with lower and less toxic doses and broadening the application of PIs to other malignancies