Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model.

HMGB1 Promotes Mitochondrial Dysfunction-Triggered Striatal Neurodegeneration via Autophagy and Apoptosis Activation.

Impairments in mitochondrial energy metabolism are thought to be involved in many neurodegenerative diseases. The mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces striatal pathology mimicking neurodegeneration in vivo. Previous studies showed that 3-NP also triggered autophagy activation and apoptosis.

Mode of allocation and social demographic factors correlate with impaired quality of life after liver transplantation.

Background: Health-related Quality of life (HRQoL) is a major goal of clinical management after liver transplantation (LTx). There is still disagreement on the effects of social-demographic factors and changes in the allocation system on HRQoL. The aim of this study was to evaluate the impact of social-demographic factors, mode of organ-allocation, waiting time and hepatocellular carcinoma (HCC) on HRQoL after LTx.

In Vivo Silencing of A20 via TLR9-Mediated Targeted SiRNA Delivery Potentiates Antitumor Immune Response.

A20 is an ubiquitin-editing enzyme that ensures the transient nature of inflammatory signaling pathways induced by cytokines like TNF-α and IL-1 or pathogens via Toll-like receptor (TLR) pathways. It has been identified as a negative regulator of dendritic cell (DC) maturation and attenuator of their immunostimulatory properties. Ex vivo A20-depleted dendritic cells showed enhanced expression of pro-inflammatory cytokines and costimulatory molecules, which resulted in hyperactivation of tumor-infiltrating T lymphocytes and inhibition of regulatory T cells.

A new qualitative proof of a result on the real Jacobian conjecture.

Let F= (f, g) : R2 → R2 be a polynomial map such that det DF(x) is different from zero for all x ∈ R2. We assume that the degrees of f and g are equal. We denote by f and G the homogeneous part of higher degree of f and g, respectively.

Selective activators of protein phosphatase 5 target the auto-inhibitory mechanism.

Protein phosphatase 5 (PP5) is an evolutionary conserved serine/threonine phosphatase. Its dephosphorylation activity modulates a diverse set of cellular factors including protein kinases and the microtubule-associated tau protein involved in neurodegenerative disorders. It is auto-regulated by its heat-shock protein (Hsp90)-interacting tetratricopeptide repeat (TPR) domain and its C-terminal α-helix.

Targeting Wnt pathway in mantle cell lymphoma-initiating cells.

Background: Mantle cell lymphoma (MCL) is an aggressive and incurable form of non-Hodgkin's lymphoma. Despite initial intense chemotherapy, up to 50% of cases of MCL relapse often in a chemoresistant form. We hypothesized that the recently identified MCL-initiating cells (MCL-ICs) are the main reason for relapse and chemoresistance of MCL.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT).

Influence of heart motion on cardiac output estimation by means of electrical impedance tomography: a case study.

Electrical impedance tomography (EIT) is a non-invasive imaging technique that can measure cardiac-related intra-thoracic impedance changes. EIT-based cardiac output estimation relies on the assumption that the amplitude of the impedance change in the ventricular region is representative of stroke volume (SV). However, other factors such as heart motion can significantly affect this ventricular impedance change.

Stereochemistry of amino acid spacers determines the pharmacokinetics of (111)In-DOTA-minigastrin analogues for targeting the CCK2/gastrin receptor.

The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L).

TRP Channels in Insect Stretch Receptors as Insecticide Targets.

Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons.

sRNA and mRNA turnover in Gram-positive bacteria.

It is widely recognized that RNA degradation plays a critical role in gene regulation when fast adaptation of cell growth is required to respond to stress and changing environmental conditions. Bacterial ribonucleases acting alone or in concert with various trans-acting regulatory factors are important mediators of RNA degradation. Here, we will give an overview of what is known about ribonucleases in several Gram-positive bacteria, their specificities and mechanisms of action.

Similar PAH fate in anaerobic digesters inoculated with three microbial communities accumulating either volatile fatty acids or methane.

Urban sludge produced on wastewater treatment plants are often contaminated by organic pollutants such as polycyclic aromatic hydrocarbons (PAH). Their removal under methanogenic conditions was already reported, but the factors influencing this removal remain unclear. Here, we determined the influence of microbial communities on PAH removal under controlled physico-chemical conditions.

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

Background: Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy.

[Organisation of emergency medicine in France].

The French emergency medicine infrastructure (structures de médecine d'urgence) ensures patients care from the very location of the distress to the appropriate hospital department: medical care in the field, by hospital clinical teams (the services mobiles d'urgence et de réanimation [SMUR]), is a key characteristic of our medical emergency response system. Response to medical distress revolves around information about not only the location and characteristics of the medical need, but also the availability of adapted hospital services. Gathering and transmitting this information is the prerogative of the service d'aide médicale d'urgence (SAMU) and its telephone dispatch center (Centre 15).

Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell-Engaging Antibody and CD8 T Cells.

Cancer stem cells (CSC) drive tumorigenesis and contribute to genotoxic therapy resistance, diffuse infiltrative invasion, and immunosuppression, which are key factors for the incurability of glioblastoma multiforme (GBM). The AC133 epitope of CD133 is an important CSC marker for GBM and other tumor entities. Here, we report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody (bsAb) that redirects human polyclonal T cells to AC133(+) GBM stem cells (GBM-SC), inducing their strong targeted lysis.

A German survey of the abdominal transplantation surgical work force.

This manuscript reports the results of a nationwide survey of transplant surgeons in Germany, including the demographics, training, position, individual case loads, center volumes, program structure, professional practice, grade of specialization, workload, work hours, salary, and career expectations. We contacted all 32 German transplant centers that perform liver, kidney, and pancreas transplantation. Surgeons engaged in transplantation were asked to reply to the survey.

Cooperative dry-electrode sensors for multi-lead biopotential and bioimpedance monitoring.

Cooperative sensors is a novel measurement architecture that allows the acquiring of biopotential signals on patients in a comfortable and easy-to-integrate manner. The novel sensors are defined as cooperative in the sense that at least two of them work in concert to measure a target physiological signal, such as a multi-lead electrocardiogram or a thoracic bioimpedance.This paper starts by analysing the state-of-the-art methods to simultaneously measure biopotential and bioimpedance signals, and justifies why currently (1) passive electrodes require the use of shielded or double-shielded cables, and (2) active electrodes require the use of multi-wired cabled technologies, when aiming at high quality physiological measurements.

Inhibition of methyltransferases accelerates degradation of cFLIP and sensitizes B-cell lymphoma cells to TRAIL-induced apoptosis.

Non-Hodgkin lymphomas (NHLs) are characterized by specific abnormalities that alter cell cycle regulation, DNA damage response, and apoptotic signaling. It is believed that cancer cells are particularly sensitive to cell death induced by tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL). However, many cancer cells show blocked TRAIL signaling due to up-regulated expression of anti-apoptotic factors, such as cFLIP.

A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis.

RsaE is the only known trans-acting small regulatory RNA (sRNA) besides the ubiquitous 6S RNA that is conserved between the human pathogen Staphylococcus aureus and the soil-dwelling Firmicute Bacillus subtilis. Although a number of RsaE targets are known in S. aureus, neither the environmental signals that lead to its expression nor its physiological role are known.

Chest CT using spectral filtration: radiation dose, image quality, and spectrum of clinical utility.

Objectives: To determine the radiation dose, image quality, and clinical utility of non-enhanced chest CT with spectral filtration.

Methods: We retrospectively analysed 25 non-contrast chest CT examinations acquired with spectral filtration (tin-filtered Sn100 kVp spectrum) compared to 25 examinations acquired without spectral filtration (120 kV). Radiation metrics were compared.

Reduction of CT beam hardening artefacts of ethylene vinyl alcohol copolymer by variation of the tantalum content: evaluation in a standardized aortic endoleak phantom.

Objectives: Our aim was to develop an aortic stent graft phantom to simulate endoleak treatment and to find a tantalum content (TC) of ethylene-vinyl-alcohol-copolymer that causes fewer computed tomography (CT) beam hardening artefacts, but still allows for fluoroscopic visualization.

Methods: Ethylene-vinyl-alcohol-copolymer specimens of different TC (10-50 %, and 100 %) were injected in an aortic phantom bearing a stent graft and endoleak cavities with simulated re-perfusion. Fluoroscopic visibility of the ethylene-vinyl-alcohol-copolymer specimens was analyzed.

CD74 interferes with the expression of fas receptor on the surface of lymphoma cells.

Background: Resistance to Fas-mediated apoptosis limits the efficacy of currently available chemotherapy regimens. We identified CD74, which is known to be overexpressed in hematological malignancies, as one of the factors interfering with Fas-mediated apoptosis.

Methods: CD74 expression was suppressed in human B-lymphoma cell lines, BJAB and Raji, by either transduction with lentivirus particles or transfection with episomal vector, both encoding CD74-specific shRNAs or non-target shRNA.

Does imaging αvβ3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy?

Unlabelled: In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of αvβ3 integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides.

Methods: Changes in (68)Ga-NODAGA-c(RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 αvβ3-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce αvβ3-positive neovasculature when transplanted into nude mice.

Comparable outcome of liver transplantation with histidine-tryptophan-ketoglutarate vs. University of Wisconsin preservation solution: a retrospective observational double-center trial.

Background: The question of whether the choice of preservation solution affects outcome after liver transplantation is still not satisfactorily answered. The purpose of this study is to examine the preservation solutions' impact on outcome after liver transplantation.

Methods: A double-center retrospective study of short- and long-term results of 3134 consecutive liver transplantations with follow-up periods up to 23 years was performed applying multivariate, risk-adjusted analyses with a subset for living-donor transplants, pediatric transplants and cases with prolonged cold ischemic times.