OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1.

Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres.

MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair.

MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity.

Comparison of N-methyl-D-aspartate receptor antibody assays using live or fixed substrates.

The diagnostic criteria for N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis require the presence of CSF antibodies against the NMDAR, whereas serum antibodies are considered specific only if accompanied by CSF antibodies. Current assays include in-house immunochemistry (IHC), or cell-based assays (CBA) which use live (L-CBA) or fixed cells (F-CBA), and commercially available fixed-cells CBA (C-CBA), but these have not been compared in parallel. We compared the L-CBA with F-CBA, C-CBA, and IHC using sera and CSFs archived from > 30,000 received for testing and previously positive by L-CBA.

Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins.

Reduced cerebrospinal fluid mitochondrial DNA is a biomarker for early-stage Parkinson's disease.

The identification of cell-free circulating mitochondrial DNA (ccf-mtDNA) in early-stage Alzheimer's disease (AD) raised the possibility that the same neurodegenerative effect could be observed in Parkinson's disease (PD). Here, and for the first time, we investigated the role of ccf-mtDNA in PD, identifying a significant reduction of ccf-mtDNA in PD patient cerebrospinal fluid (CSF) when compared to controls. Our data demonstrates that CSF ccf-mtDNA is not only a powerful biomarker for PD, but, given that the effect is also observed in AD, is likely a biomarker for neurodegeneration.

Glut1 deficiency syndrome: Absence epilepsy and La Soupe du Jour.

For some time, paediatric neurologists have recognised glucose transporter type 1 (GluT1) deficiency syndrome as a cause of intractable infantile seizures, microcephaly, developmental delay and hypoglycorrhachia in the presence of a normal plasma glucose. It is caused by mutations in the SLC2A1 gene, coding for GluT1, leading to a reduction in the available glucose transporter sites; it responds to the ketogenic diet. Recently, a wider spectrum of seizure syndromes have been associated with functional impairment of glucose transport caused by SLC2A1 mutations.

Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.

Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency.

Glucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause of genetic generalized epilepsy. We previously reported that >10% (4 of 34) of a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses a new cohort of 55 patients with EOAE to confirm that finding.

[Alcohol consumption patterns and behaviour among people using the health care system in Lower-Normandy].

A national study on the prevalence of excessive alcohol consumption behaviour was undertaken throughout France. The results presented in this paper are those from Lower-Normandy. Two surveys were carried out: one among patients of general practitioners, and another among those in hospitals.

[Regional evaluation of long-term care facilities for the elderly].

The increase in the total number of very elderly people demands the precision and specification of the needs of long-term care structures in the coming years. A survey conducted in Lower-Normandy is presented and described. Questionnaires were sent to directors of residence homes and nursing homes in order to investigate their operations and their problems.

Role of anxiety and depression in the onset of spontaneous preterm labor.

The aim of this cohort study conducted in France in 1997-1998 was to investigate the effects of antenatal anxiety and depression on spontaneous preterm labor. A consecutive series of 634 pregnant women with singleton pregnancies was included. Anxiety and depression were assessed using self-administered questionnaires: Spielberger's State-Trait Anxiety Inventory and the Edinburgh depression scale.

[Computer-assisted instruction applied to preventive medicine in adolescents: bibliographic analysis and perspectives].

Computer-assisted instruction (CAI) for adolescent health promotion is still underused in France. We analysed the literature on existing systems in terms of current issues, techniques used, efficacy and difficulties experienced. All the authors noted that youth show a great interest in computer-assisted instruction and that they have made progress in their knowledge of health related risks.

[Requirements for the successful implementation of unity of care: study of a computer-assisted dispensation of pharmaceuticals].

Purpose: Even though computerized workstations bring undisputed benefits in nursing units, introducing them is still hard when most of the staff members have to share the workstation. We took advantage of the implementation of the drug prescription software SAUPHIX in a nephrology department to better define the encountered difficulties. The workstation described in this paper is shared by physicians who enter their prescriptions (proprietary names, doses, routes of administration), nurses who use dosage schedules for drug administration, and the chemist who has authority to control prescription orders.

[Isolation rooms in the psychiatric environment].

To date, there has been no survey concerning psychiatric isolation rooms in France. We conducted a mail survey in 1993 involving all adult psychiatric care catchment areas covering the French departments. The survey revealed an estimated number of 1560 isolation rooms.

[Computer records of anesthesiology information. Evaluation of the operative risk].

This work proposed: 1) to record all the anaesthetic information in the SYSRES system, 2) to carry out a global numerical evaluation of the surgical risks in the form of a coefficient (CORI) defining a probability of complications thanks to a table established from several hundred case-files. This method has several purposes: the carrying-out of very quick summaries of case-files, and of statistical studies, several of which could be used as a basis in scientific work and, most of all, allow an increase in the safety of the patients.