Ductular reaction promotes intrahepatic angiogenesis through Slit2-Roundabout 1 signaling.

Background And Aims: Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis.

Clinical outcomes of combined Preserflo Microshunt implantation and cataract surgery in open-angle glaucoma patients.

To assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months.

Cytolethal Distending Toxin Promotes Replicative Stress Leading to Genetic Instability Transmitted to Daughter Cells.

The cytolethal distending toxin (CDT) is produced by several Gram-negative pathogenic bacteria. In addition to inflammation, experimental evidences are in favor of a protumoral role of CDT-harboring bacteria such as , , or . CDT may contribute to cell transformation and carcinogenesis in mice models, through the genotoxic action of CdtB catalytic subunit.

Exposure to the Fungicide Captan Induces DNA Base Alterations and Replicative Stress in Mammalian Cells.

The classification of the fungicide captan (CAS Number: 133-06-2) as a carcinogen agent is presently under discussion. Despite the mutagenic effect detected by the Ames test and carcinogenic properties observed in mice, the genotoxicity of this pesticide in humans is still unclear. New information is needed about its mechanism of action in mammalian cells.

Around and beyond 53BP1 Nuclear Bodies.

Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined.

Parametric modeling of wideband piezoelectric polymer sensors: Design for optoacoustic applications.

In this work, we present a three-dimensional model for the design of wideband piezoelectric polymer sensors which includes the geometry and the properties of the transducer materials. The model uses FFT and numerical integration techniques in an explicit, semi-analytical approach. To validate the model, we made electrical and mechanical measurements on homemade sensors for optoacoustic applications.

Lack of relationship between plasma levels of escitalopram and QTc-interval length.

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms.

CHK1 as a therapeutic target to bypass chemoresistance in AML.

The nucleoside analog cytarabine, an inhibitor of DNA replication fork progression that results in DNA damage, is currently used in the treatment of acute myeloid leukemia (AML). We explored the prognostic value of the expression of 72 genes involved in various aspects of DNA replication in a set of 198 AML patients treated by cytarabine-based chemotherapy. We unveiled that high expression of the DNA replication checkpoint gene CHEK1 is a prognostic marker associated with shorter overall, event-free, and relapse-free survivals and determined that the expression of CHEK1 can predict more frequent and earlier postremission relapse.

Hepatic Primary and Secondary Cholesterol Deposition and Damage in Niemann-Pick Disease.

Niemann-Pick C disease is a neurovisceral disorder caused by mutations in the NPC gene that result in systemic accumulation of intracellular cholesterol. Although neurodegeneration defines the disease's severity, in most patients it is preceded by hepatic complications such as cholestatic jaundice or hepatomegaly. To analyze the contribution of the hepatic disease in Niemann-Pick C disease progression and to evaluate the degree of primary and secondary hepatic damage, we generated a transgenic mouse with liver-selective expression of NPC1 from embryonic stages.

AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation.

Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution.

A role for DNA polymerase θ in the timing of DNA replication.

Although DNA polymerase θ (Pol θ) is known to carry out translesion synthesis and has been implicated in DNA repair, its physiological function under normal growth conditions remains unclear. Here we present evidence that Pol θ plays a role in determining the timing of replication in human cells. We find that Pol θ binds to chromatin during early G1, interacts with the Orc2 and Orc4 components of the Origin recognition complex and that the association of Mcm proteins with chromatin is enhanced in G1 when Pol θ is downregulated.

Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder.

Introduction: Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients.

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs).

Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity.

Lipid droplets (LDs) are dynamic organelles that collect, store, and supply lipids [1]. LDs have a central role in the exchange of lipids occurring between the cell and the environment and provide cells with substrates for energy metabolism, membrane synthesis, and production of lipid-derived molecules such as lipoproteins or hormones. However, lipid-derived metabolites also cause progressive lipotoxicity [2], accumulation of reactive oxygen species (ROS), endoplasmic reticulum stress, mitochondrial malfunctioning, and cell death [2].

Topical intraocular pressure therapy effects on pregnancy.

Purpose: To assess the course of intraocular pressure (IOP), visual field progression, and adverse effects of antiglaucoma medication used during pregnancy.

Methods: Thirteen eyes of eight patients with glaucoma were examined. Their clinical records were reviewed to compare IOP, number of medications, and visual field indices (VFI) before, during, and after pregnancy using a two-tailed paired t-test.

[Comparing central corneal thickness measured using ultrasound pachymetry and the Pentacam in healthy subjects and patients with primary open-angle glaucoma].

Purpose: To determine the capacity for measurement of central corneal thickness by ultrasound pachymetry and by Pentacam (pachymetry at the pupillary axis and minimum corneal pachymetry) to discriminate between healthy controls and patients with primary open-angle glaucoma.

Methods: Measurements of the left eyes of 123 control subjects and 128 glaucomatous patients were taken. Differences between the two data sets for each variable were identified using a t-test for independent samples.

[Comparison of Goldmann applanation and dynamic contour tonometry measurements: effects of corneal morphometry].

Objectives: To compare intraocular pressure (IOP) measurements made by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT).

Methods: IOPs were measured by GAT and DCT in 63 eyes of 63 healthy subjects. A comparison was made by intraclass correlation coefficient.

Comparing corneal variables in healthy subjects and patients with primary open-angle glaucoma.

Purpose: This study was designed to identify possible differences between healthy subjects and patients with primary open-angle glaucoma (POAG) in keratometry, central corneal thickness, overall corneal thickness, mean thickness of a circular zone centered at the corneal apex of 1-mm radius (zone I), and mean thickness of several concentric rings also centered at the apex of 1-mm width (zones II to VI, respectively).

Methods: These variables were recorded in 126 healthy subjects and 130 patients with POAG. Corneal thicknesses and the power of the flattest and steepest axes were compared between the two populations using a t-test and the position of the flattest axis using a Mann-Whitney U test.

DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability.

"Replicative stress" is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n=206; United Kingdom, n=117) of patients with previously untreated primary breast cancers.

Comparison of ocular hypotensive actions of fixed combinations of brimonidine/timolol and dorzolamide/timolol.

Objective: To compare brimonidine/timolol fixed combination (BrTFC; Combigan *) with dorzolamide/timolol fixed combination (DTFC; Cosopt dagger) in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG).

Methods: This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.

Upregulation of the CDC25A phosphatase down-stream of the NPM/ALK oncogene participates to anaplastic large cell lymphoma enhanced proliferation.

Here, we demonstrate that the expression of the dual specificity phosphatase CDC25A, a key regulator of cell cycle progression, is deregulated in Ba/F3 cells expressing the oncogenic protein NPM/ALK and in human cell lines derived from NPM/ALK-positive anaplastic large cell lymphomas (ALCL). Both transcriptional and post-translational mechanisms account for the constitutive expression of the protein, and the PI3K/Akt pathway is essential for this process. Importantly, pharmacological inhibition of CDC25 dramatically inhibits the proliferation of NPM/ALK-expressing cells, while moderately affecting the proliferation of control Ba/F3 cells.

Comparison of rebound tonometer and Goldmann handheld applanation tonometer in congenital glaucoma.

Purpose: To compare intraocular pressure (IOP) measurements obtained using the rebound tonometer (RBT) and the handheld Goldmann applanation tonometer (Perkins) in children with congenital glaucoma.

Methods: Using both tonometers, the IOP was prospectively determined in 68 eyes of 68 patients with congenital glaucoma aged 3 to 13 years. Corneal curvature, central corneal thickness (CCT), and axial length were also measured in each patient.

CDC25A: a rebel within the CDC25 phosphatases family?

CDC25 dual specificity phosphatases activate the cyclin-dependent kinase complexes, allowing timely ordered progression through out the different phases of the eukaryotic cell cycle. In humans, there are three genes coding for the CDC25A, B and C proteins with both different and redundant specificities and regulations. The CDC25A member of this family acts during the G1 phase and at the G1/S transition by activating the CDK2/cyclin E and CDK2/cyclin A complexes, a function apparently not shared by the other members.