Are Thoracotomy and/or Intrathoracic Anastomosis Still Predictors of Postoperative Mortality After Esophageal Cancer Surgery?: A Nationwide Study.

Background: Intrathoracic (vs cervical) anastomosis and a thoracotomy (vs absence) have previously been associated with increasing postoperative mortality (POM). Recent improvements in surgical practices and perioperative management may have changed these dogmas.

Objectives: The aim of this study was to evaluate the impact of performing intrathoracic anastomosis and/or thoracotomy on POM after esophageal cancer surgery in recent years.

Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A receptor.

The development of adenosine A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A receptor.

Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression.

A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression.

GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2.

Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise the most common cause of familial Parkinson's disease (PD), and sequence variants modify risk for sporadic PD. Previous studies indicate that LRRK2 interacts with microtubules (MTs) and alters MT-mediated vesicular transport processes. However, the molecular determinants within LRRK2 required for such interactions have remained unknown.

Same-day discharge in benign esophageal surgery: a prospective cohort study.

Day-case esophageal surgery has been demonstrated to be safe in small prospective cohorts and only for laparoscopic fundoplication. The aims of this study are to assess the feasibility and safety of a large series of esophageal day-case surgeries, including laparoscopic Nissen fundoplication (LNF), Zenker diverticulectomy (ZD), and laparoscopic Heller myotomy (LHM) and to compare the outcomes among three procedures.This was a prospective, observational study of selected patients who underwent day-case LNF, ZD, and LHM between 2003 and 2013.

Surgically treated oesophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes.

Background: The objectives of this study were to compare peri-operative and long-term outcomes from oesophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary (PEC) and among ECRF patients and (ii) radiotherapy-induced (RIEC) versus non-radiotherapy-induced EC (NRIEC).

Methods: Data were collected from 30 European centres from 2000 to 2010. Two thousand four hundred eighty nine EC patients surgically treated were included in the PEC group and 136 in the ECRF group, NRIEC group (n = 61) and RIEC group (n = 75).

Therapeutic potential of autophagy-enhancing agents in Parkinson's disease.

Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson's Disease (PD). Genetic studies have identified mutations in genes encoding for components of the autophagy-lysosomal pathway (ALP), including glucosidase beta acid 1 (GBA1), that are associated with increased risk for developing PD. Observations in PD brain tissue suggest an aberrant regulation of autophagy associated with the aggregation of α-synuclein (α-syn).

Is there a role for ghrelin in central dopaminergic systems? Focus on nigrostriatal and mesocorticolimbic pathways.

The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer.

Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner.

Lactate is an essential component of carbon metabolism in mammals. Recently, lactate was shown to signal through the G protein coupled receptor 81 (GPR81) and to thus modulate inflammatory processes. This study demonstrates that lactate inhibits pro-inflammatory signaling in a GPR81-independent fashion.

AMPK in Neurodegenerative Diseases.

Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation.

Development of the neurons controlling fertility in humans: new insights from 3D imaging and transparent fetal brains.

Fertility in mammals is controlled by hypothalamic neurons that secrete gonadotropin-releasing hormone (GnRH). These neurons differentiate in the olfactory placodes during embryogenesis and migrate from the nose to the hypothalamus before birth. Information regarding this process in humans is sparse.

Mitochondrial oxidative phosphorylation controls cancer cell's life and death decisions upon exposure to MAPK inhibitors.

Although MAPK pathway inhibitors are becoming a promising anticancer strategy, they are insufficient to fully eliminate cancer cells and their long-term efficacy is strikingly limited in patients with BRAF-mutant melanomas. It is well established that BRAF inhibitors (BRAFi) hamper glucose uptake before the apparition of cell death. Here, we show that BRAFi induce an extensive restructuring of mitochondria including an increase in mitochondrial activity and biogenesis associated with mitochondrial network remodeling.

RNA-binding disturbances as a continuum from spinocerebellar ataxia type 2 to Parkinson disease.

CAG triplet expansions in Ataxin-2 gene (ATXN2) cause spinocerebellar ataxia type 2 and have a role that remains to be clarified in Parkinson's disease (PD). To study the molecular events associated with these expansions, we sequenced them and analyzed the transcriptome from blood cells of controls and three patient groups diagnosed with spinocerebellar ataxia type 2 (herein referred to as SCA2c) or PD with or without ATXN2 triplet expansions (named SCA2p). The transcriptome profiles of these 40 patients revealed three main observations: i) a specific pattern of pathways related to cellular contacts, proliferation and differentiation associated with SCA2p group, ii) similarities between the SCA2p and sporadic PD groups in genes and pathways known to be altered in PD such as Wnt, Ephrin and Leukocyte extravasation signaling iii) RNA metabolism disturbances with "RNA-binding" and "poly(A) RNA-binding" as a common feature in all groups.

Is Centralization Needed for Esophageal and Gastric Cancer Patients With Low Operative Risk?: A Nationwide Study.

Objective: To investigate the impact of center volume on postoperative mortality (POM) according to patient condition.

Background: Centralization has been shown to improve POM in esophageal and, to a lesser extent, gastric cancer surgery; however, the benefit of centralization for patients with low operative risk is questionable.

Methods: All consecutive patients who underwent esophageal or gastric cancer surgery between 2010 and 2012 in France were included (N = 11,196).

The MAPT gene is differentially methylated in the progressive supranuclear palsy brain.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter.

Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity.

Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.

Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response.

Background: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been recently reported. Dendritic cells (DC) are professional antigen presenting cells that drive T-cells differentiation and activation.

New Insights in Anorexia Nervosa.

Anorexia nervosa (AN) is classically defined as a condition in which an abnormally low body weight is associated with an intense fear of gaining weight and distorted cognitions regarding weight, shape, and drive for thinness. This article reviews recent evidences from physiology, genetics, epigenetics, and brain imaging which allow to consider AN as an abnormality of reward pathways or an attempt to preserve mental homeostasis. Special emphasis is put on ghrelino-resistance and the importance of orexigenic peptides of the lateral hypothalamus, the gut microbiota and a dysimmune disorder of neuropeptide signaling.

Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus.

Unlabelled: Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them.

Recent improvements in the management of esophageal anastomotic leak after surgery for cancer.

Anastomotic leakage following total gastrectomy or esophagectomy is a significant complication that considerably increases postoperative mortality. The location of the anastomosis together with the anatomy of the esophagus explains the severity of this complication. Surgical knowledge should include general and specific predictive factors of leakage to avoid any technical-related cause of leakage.

Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N,N'-disubstituted piperazine derivatives.

The performances of three neutral static coatings (hydroxypropyl cellulose, polyethylene oxide and poly(N,N-dimethylacrylamide) have been evaluated in order to determine the binding constants of the complexes formed between four polycationic compounds (piperazine derivatives) and four cyclodextrins of pharmaceutical interest (β-CD, HP-β-CD, Me-β-CD and sulfobutyl ether-β-CD) by affinity capillary electrophoresis. The physically-adsorbed poly(N,N-dimethylacrylamide) coating proves to be the more efficient to mask the silanol groups of the capillary wall since the lowest electroosmotic flow was measured for this coating. Moreover, it drastically reduces the adsorption of the compounds since it allows a correct repeatability of their migration time, higher efficiencies of the peaks and no baseline shift.

miR-21-5p renal expression is associated with fibrosis and renal survival in patients with IgA nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN.

AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo.

Neurofibrillary tangles (NFTs) are the pathological hallmark of neurodegenerative diseases commonly known as tauopathies. NFTs result from the intracellular aggregation of abnormally and hyperphosphorylated tau proteins. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status.