MicroRNA-Mediated Metabolic Shaping of the Tumor Microenvironment

The metabolism of cancer cells is generally very different from what is found in normal counterparts. However, in a tumor mass, the continuous crosstalk and competition for nutrients and oxygen among different cells lead to metabolic alterations, not only in cancer cells, but also in the different stromal and immune cells of the tumor microenvironment (TME), which are highly relevant for tumor progression. MicroRNAs (miRs) are small non-coding RNAs that silence their mRNA targets post-transcriptionally and are involved in numerous physiological cell functions as well as in the adaptation to stress situations. Importantly, miRs can also be released via extracellular vesicles (EVs) and, consequently, take part in the bidirectional communication between tumor and surrounding cells under stress conditions. Certain miRs are abundantly expressed in stromal and immune cells where they can regulate various metabolic pathways by directly suppressing enzymes or transporters as well as by controlling important regulators (such as transcription factors) of metabolic processes. In this review, we discuss how miRs can induce metabolic reprogramming in stromal (fibroblasts and adipocytes) and immune (macrophages and T cells) cells and, in turn, how the biology of the different cells present in the TME is able to change. Finally, we debate the rebound of miR-dependent metabolic alterations on tumor progression and their implications for cancer management

The Current State of Validation of Administrative Healthcare Databases in Italy: A Systematic Review

Background: Administrative healthcare databases are widely present in Italy. Our aim was to describe the current state of healthcare databases validity in terms of discharge diagnoses (according to the International Classification of Diseases, ICD-9 code) and their output in terms of research.Methods: A systematic search of electronic databases including Medline and Embase (1995-2013) and of local sources was performed. Inclusion criteria were: healthcare databases in any Italian territory routinely and passively collecting data; medical investigations or procedures at patient level data; the use of a validation process. The quality of studies was evaluated using the STARD criteria. Citations of the included studies were explored using Scopus and Google Scholar.Results: The search strategy allowed the identification of 16 studies of which 3 were in Italian. Thirteen studies used regional administrative databases from Lombardia, Piemonte, Lazio, Friuli-Venezia Giulia and Veneto. The ICD-9 codes of the following diseases were successfully validated: amyotrophic lateral sclerosis (3 studies in four different regional administrative databases), stroke (3 studies), gastrointestinal bleeding (1 study), thrombocytopenia (1 study), epilepsy (1 study), infection (1 study), chronic obstructive pulmonary disease (1 study), Guillain-Barre syndrome (1 study), and cancer diseases (4 studies). The quality of reporting was variable among the studies. Only 6 administrative databases produced further research related to the validated ICD-9 codes.Conclusion: Administrative healthcare databases in Italy need an extensive process of validation for multiple diagnostic codes to perform high quality epidemiological and health services research

Guidelines on the management of abdominal aortic aneurysms: updates from the Italian Society of Vascular and Endovascular Surgery (SICVE)

The objective of these Guidelines was to revise and update the previous 2016 Italian Guidelines on Abdominal Aortic Aneurysm Disease, in accordance with the National Guidelines System (SNLG), to guide every practitioner toward the most correct management pathway for this pathology. The methodology applied in this update was the GRADE-SIGN version methodology, following the instructions of the AGREE quality of reporting checklist as well. The first methodological step was the formulation of clinical questions structured according to the PICO (Population, Intervention, Comparison, Outcome) model according to which the Recommendations were issued. Then, systematic reviews of the Literature were carried out for each PICO question or for homogeneous groups of questions, followed by the selection of the articles and the assessment of the methodological quality for each of them using qualitative checklists. Finally, a Considered Judgment form was filled in for each clinical question, in which the features of the evidence as a whole are assessed to establish the transition from the level of evidence to the direction and strength of the recommendations. These guidelines outline the correct management of patients with abdominal aortic aneurysm in terms of screening and surveillance. Medical management and indication for surgery are discussed, as well as preoperative assessment regarding patients' background and surgical risk evaluation. Once the indication for surgery has been established, the options for traditional open and endovascular surgery are described and compared, focusing specifically on patients with ruptured abdominal aortic aneurysms as well. Finally, indications for early and late postoperative follow-up are explained. The most recent evidence in the Literature has been able to confirm and possibly modify the previous recommendations updating them, likewise to propose new recommendations on prospectively relevant topics

Guideline on carotid surgery for stroke prevention: updates from the Italian Society of Vascular and Endovascular Surgery. A trend towards personalized medicine

Background: This guideline (GL) on carotid surgery as updating of "Stroke: Italian guidelines for Prevention and Treatment" of the ISO-SPREAD Italian Stroke Organization-Group, has recently been published in the National Guideline System and shared with the Italian Society of Vascular and Endovascular Surgery (SICVE) and other Scientific Societies and Patient's Association. Methods: GRADE-SIGN version, AGREE quality of reporting checklist. Clinical questions formulated according to the PICO model. Recommendations developed based on clinical questions by a multidisciplinary experts' panel and patients' representatives. Systematic reviews performed for each PICO question. Considered judgements filled by assessing the evidence level, direction, and strength of the recommendations. Results: The panel provided indications and recommendations for appropriate, comprehensive, and individualized management of patients with carotid stenosis. Diagnostic and therapeutic processes of the best medical therapy, carotid endarterectomy (CEA), carotid stenting (CAS) according to the evidences and the judged opinions were included. Symptomatic carotid stenosis in elective and emergency, asymptomatic carotid stenosis, association with ischemic heart disease, preoperative diagnostics, types of anesthesia, monitoring in case of CEA, CEA techniques, comparison between CEA and CAS, post-surgical carotid restenosis, and medical therapy are the main topics, even with analysis of uncertainty areas for risk-benefit assessments in the individual patient (personalized medicine [PM]). Conclusions: This GL updates on the main recommendations for the most appropriate diagnostic and medical-surgical management of patients with atherosclerotic carotid artery stenosis to prevent ischemic stroke. This GL also provides useful elements for the application of PM in good clinical practice

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α–dependent microRNA (miR)–210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210–based therapeutic and diagnostic strategies

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Tracker Operation and Performance at the Magnet Test and Cosmic Challenge

During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI