Regulation of kinesin-1 activity by the effectors PipB2 and SifA.

is an intracellular bacterial pathogen. The formation of its replication niche, which is composed of a vacuole associated with a network of membrane tubules, depends on the secretion of a set of bacterial effector proteins whose activities deeply modify the functions of the eukaryotic host cell. By recruiting and regulating the activity of the kinesin-1 molecular motor, effectors PipB2 and SifA play an essential role in the formation of the bacterial compartments.

Clinical trials in REM sleep behavioural disorder: challenges and opportunities.

The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results.

Immune Checkpoint Inhibitors in Transplantation-A Case Series and Comprehensive Review of Current Knowledge.

Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series.

Lift and VAAFT for high trans-sphincteric anal fistula: a single center retrospective analysis.

Purpose: The management of complex anal fistulas remains a challenge, mainly due to the considerable risk of incontinence. We compared LIFT and VAAFT in the treatment of complex anal fistulas in terms of healing time, recurrence, continence, morbidity, and postoperative pain, focusing also on patients with local abscess at the time of surgery.

Methods: We include all patients with high trans-sphincteric anal fistula even with abscess at the time of surgery.

Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT-Dependent Activation of the Aryl Hydrocarbon Receptor.

Macrophages can either promote or resolve inflammatory responses, and their polarization state is modulated by peripheral serotonin (5-hydroxytryptamine [5-HT]). In fact, pro- and anti-inflammatory macrophages differ in the expression of serotonin receptors, with 5-HT and 5-HT expression restricted to M-CSF-primed monocyte-derived macrophages (M-MØ). 5-HT drives the acquisition of profibrotic and anti-inflammatory functions in M-MØ, whereas 5-HT prevents the degeneration of spinal cord mononuclear phagocytes and modulates motility of murine microglial processes.

Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with -internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The () gene is mutated in 25-30% of patients with acute myeloid leukemia (AML). Because of the poor prognosis associated with -internal tandem duplication mutated AML, allogeneic hematopoietic stem-cell transplantation (SCT) was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays.

Subtelomeres as Specialized Chromatin Domains.

Specificities associated with chromosomal linearity are not restricted to telomeres. Here, recent results obtained on fission and budding yeast are summarized and an attempt is made to define subtelomeres using chromatin features extending beyond the heterochromatin emanating from telomeres. Subtelomeres, the chromosome domains adjacent to telomeres, differ from the rest of the genome by their gene content, rapid evolution, and chromatin features that together contribute to organism adaptation.

Author Correction: Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Optimal management of ascites.

Ascites is the most common complication of cirrhosis, which develops in 5%-10% of patients per year. Its management is based on symptomatic measures including restriction of sodium intake, diuretics and paracentesis. Underlying liver disease must always be treated and may improve ascites.

Hostility, depression and incident cardiac events in the GAZEL cohort.

Background: Psychological factors such as hostility and depression have been associated with cardiovascular disease. However, their role in predicting incident cardiac events independently one of another is not clear.

Methods: Among 10,304 GAZEL middle-aged workers free of cardiovascular diseases in 1993, 581 incident cardiac events were validated from 1994-2014.

Development of a Standardized Chemiluminescence Immunoassay for the Detection of Autoantibodies Against Human M-Type Phospholipase A2 Receptor in Primary Membranous Nephropathy.

Introduction: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R) are important markers in the diagnosis and monitoring of primary membranous nephropathy (pMN). For the detection of anti-PLA2R autoantibodies, a standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA) are widely used, the former providing higher sensitivity but lacking a finely graduated quantification of antibody titers. In this study, we evaluated the diagnostic performance characteristics of a novel standardized chemiluminescence immunoassay (ChLIA) by comparison with the established anti-PLA2R test systems.

Typical Familial Mediterranean Fever associated with the heterozygous missense sequence p.T577N variant of the MEFV gene: Report on two Northern European Caucasians relatives in France.

Introduction: Familial Mediterranean fever is the most frequent monogenic auto-inflammatory disorder that mostly affects Mediterranean population. Although this auto-inflammatory disease has historically been described as a recessive genetic disorder with homozygous or compound heterozygous mutations in the MEFV gene, an increasing number of cases are described with the detection of new single MEFV gene heterozygous mutations with modern molecular techniques.

Case Description: We report the cases of Caucasian French descent father and daughter who exhibited joint and abdominal inflammatory attacks resembling Familial Mediterranean Fever.

Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study.

Background: For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation.

Methods: This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker.

Stem Cell DNA Damage and Genome Mutation in the Context of Aging and Cancer Initiation.

Adult stem cells fuel tissue homeostasis and regeneration through their unique ability to self-renew and differentiate into specialized cells. Thus, their DNA provides instructions that impact the tissue as a whole. Since DNA is not an inert molecule, but rather dynamic, interacting with a myriad of chemical and physical factors, it encounters damage from both endogenous and exogenous sources.

The Golgi apparatus and cell polarity: Roles of the cytoskeleton, the Golgi matrix, and Golgi membranes.

Membrane trafficking plays a crucial role in cell polarity by directing lipids and proteins to specific subcellular locations in the cell and sustaining a polarized state. The Golgi apparatus, the master organizer of membrane trafficking, can be subdivided into three layers that play different mechanical roles: a cytoskeletal layer, the so-called Golgi matrix, and the Golgi membranes. First, the outer regions of the Golgi apparatus interact with cytoskeletal elements, mainly actin and microtubules, which shape, position, and orient the organelle.

Impact of Italian Score for Organ Allocation System on Deceased Donor Liver Transplantation: A Monocentric Competing Risk Time-to-Event Analysis.

Background: Liver transplantation (LT) is the only definitive and curative treatment for patients with end-stage liver disease and hepatocellular carcinoma. We aimed to evaluate the impact of the Italian score for organ allocation (ISO) in terms of the waiting-list mortality, probability of LT, and patient survival after LT.

Patient And Methods: All of the adult patients on the waiting list for LT at our institute from January 2014 to December 2017 were included in the study.