Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet.

Objective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA).

Laparoscopic appendectomy vs antibiotic therapy for acute appendicitis: a propensity score-matched analysis from a multicenter cohort study.

Acute appendicitis (AA) is among the most common causes of acute lower abdominal pain leading patients to the emergency department. Significant debate remains on whether AA should be operated or not. A propensity score-matched analysis was performed in seven Italian Hospitals, with the aim to assess safety and feasibility both nonoperative management with antibiotics (AT) and surgical therapy with appendectomy (ST) for patients with AA.

A probabilistic network for the diagnosis of acute cardiopulmonary diseases.

In this paper, the development of a probabilistic network for the diagnosis of acute cardiopulmonary diseases is presented in detail. A panel of expert physicians collaborated to specify the qualitative part, which is a directed acyclic graph defining a factorization of the joint probability distribution of domain variables into univariate conditional distributions. The quantitative part, which is a set of parametric models defining these univariate conditional distributions, was estimated following the Bayesian paradigm.

Long-term applicability of the new ILAE definition of epilepsy. Results from the PRO-LONG study.

Objective: The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10-year period. Long-term follow-up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice.

Methods: Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow-up of 10 years.

Antiepileptic drug discontinuation by people with epilepsy in the general population.

Objective: Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation.

Methods: The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions.

Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients.

Introduction: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line.

Patients And Methods: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B).

Innate and adaptive immunity in human epilepsies.

Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology.

Introduction to the 2nd Meeting on Immunity and Inflammation in Epilepsy (IIE2016).

We report about the main topics presented during this meeting which was devoted to discuss the new emerging evidence for a role of immune- and inflammation-related mechanisms in various autoimmune and nonautoimmune forms of epilepsy. Major emphasis was given to novel immune/inflammatory mechanisms contributing to seizures and neurological comorbidities as well as to the discovery and validation of noninvasive biomarkers of brain inflammation which may be used to monitor epileptogenesis and predict the therapeutic effects of treatments. The key question was whether our scientific community is ready for the translation of the results of laboratory research to clinical studies, and how to best design clinical trials of anti-inflammatory drugs with potential disease-modifying effects.

A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action.

The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs.

The Hematocrit Affects the Volume of Plasma Treated With Coupled Plasma Filtration and Adsorption With Predilution.

Coupled plasma filtration and adsorption (CPFA) is an extracorporeal blood purification technique proposed for the treatment of septic-shock. By removing pro- and anti-inflammatory mediators from plasma, CPFA is supposed to have a therapeutic effect on the abnormal inflammatory response seen in this condition. Recently, blood predilution with citrate solution has been adopted to prevent clotting in the CPFA circuit-one of the main problems of the technique.

FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients.

Background: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro.

Contribution of tumor endothelial cells to drug resistance: anti-angiogenic tyrosine kinase inhibitors act as p-glycoprotein antagonists.

Tumor endothelial cells (TEC) differ from the normal counterpart, in both gene expression and functionality. TEC may acquire drug resistance, a characteristic that is maintained in vitro. There is evidence that TEC are more resistant to chemotherapeutic drugs, substrates of ATP-binding cassette (ABC) transporters.

The renal phenotype of allopurinol-treated HPRT-deficient mouse.

Excess of uric acid is mainly treated with xanthine oxidase (XO) inhibitors, also called uricostatics because they block the conversion of hypoxanthine and xanthine into urate. Normally, accumulation of upstream metabolites is prevented by the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. The recycling pathway, however, is impaired in the presence of HPRT deficiency, as observed in Lesch-Nyhan disease.

Breast and renal cancer-Derived endothelial colony forming cells share a common gene signature.

Background: Neovascularisation supports the metastatic switch in many aggressive solid cancers. Tumour neovessels are mostly lined by endothelial cells sprouting from nearby capillaries, but they could also be contributed by circulating endothelial progenitor cells (EPCs). However, scant information is available about tumour-derived EPCs.

WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities.

Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need.

Circulating miRNA landscape identifies miR-1246 as promising diagnostic biomarker in high-grade serous ovarian carcinoma: A validation across two independent cohorts.

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve HGSOC cure rate. Sera from 168 HGSOC patients and 65 healthy controls were gathered together from two independent collections and stratified into a training set, for miRNA marker identification, and a validation set, for data validation.

Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment.

Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection).

Implementing an evidence-based computerized decision support system linked to electronic health records to improve care for cancer patients: the ONCO-CODES study protocol for a randomized controlled trial.

Background: Computerized decision support systems (CDSSs) are computer programs that provide doctors with person-specific, actionable recommendations, or management options that are intelligently filtered or presented at appropriate times to enhance health care. CDSSs might be integrated with patient electronic health records (EHRs) and evidence-based knowledge.

Methods/design: The Computerized DEcision Support in ONCOlogy (ONCO-CODES) trial is a pragmatic, parallel group, randomized controlled study with 1:1 allocation ratio.

On-going electroencephalographic rhythms related to cortical arousal in wild-type mice: the effect of aging.

Resting state electroencephalographic (EEG) rhythms reflect the fluctuation of cortical arousal and vigilance in a typical clinical setting, namely the EEG recording for few minutes with eyes closed (i.e., passive condition) and eyes open (i.

The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines.

Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines.