Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

Background: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers.

Methods: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH).

OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants.

Patients with rare or ultra-rare genetic diseases, which affect 350 million people worldwide, may experience a diagnostic odyssey. High-throughput sequencing leads to an etiological diagnosis in up to 50% of individuals with heterogeneous neurodevelopmental or malformation disorders. There is a growing interest in additional omics technologies in translational research settings to examine the remaining unsolved cases.

The Economic, Medical and Psychosocial Consequences of Whole Genome Sequencing for the Genetic Diagnosis of Patients With Intellectual Disability: The DEFIDIAG Study Protocol.

Like other countries, France has invested in a national medical genomics program. Among the four pilot research studies, the DEFIDIAG project focuses on the use of whole genome sequencing (WGS) for patients with intellectual disability (ID), a neurodevelopmental condition affecting 1-3% of the general population but due to a plethora of genes. However, the access to genomic analyses has many potential individual and societal issues in addition to the technical challenges.

Unusual Brain MRI Pattern in 2 Patients with COVID-19 Acute Respiratory Distress Syndrome.

We report the cases of 2 patients hospitalized in our intensive care unit with confirmed coronavirus disease 2019 infection in whom brain MR imaging showed an unusual DWI pattern with nodular and ring-shaped lesions involving the periventricular and deep white matter. We discuss the possible reasons for these findings and their relationship to the infection.

Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth.

Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques not associated with efficient SIV-specific CD8+ T-cell responses.

Unlabelled: The spontaneous control of human and simian immunodeficiency viruses (HIV/SIV) is typically associated with specific major histocompatibility complex (MHC) class I alleles and efficient CD8(+) T-cell responses, but many controllers maintain viral control despite a nonprotective MHC background and weak CD8(+) T-cell responses. Therefore, the contribution of this response to maintaining long-term viral control remains unclear. To address this question, we transiently depleted CD8(+) T cells from five SIV-infected cynomolgus macaques with long-term viral control and weak CD8(+) T-cell responses.

Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses B cell responses.

Inhibition of B cells constitutes a rational approach for treating B cell-mediated disorders. We demonstrate in this article that the engagement of the surface Ig-like transcript 2 (ILT2) inhibitory receptor with its preferential ligand HLA-G is critical to inhibit B cell functions. Indeed, ILT2-HLA-G interaction impedes both naive and memory B cell functions in vitro and in vivo.

[From PICO to search terms on the Internet: how to find relevant information? New coxibs: do they have a better gastrointestinal safety?].

In the first article of this series, we have shown how to translate a clinical problem into a well built question, by creating a PICO (Patient--Intervention--Comparison--Outcome). In this second article, we will explain how to transform the PICO in English search terms for use on the internet. We use these terms in the different databases to find the answer to the following clinical problem: "In patients aged 65 or over with hip osteoarthritis, and a history of peptic ulcer, is the risk of a new peptic ulcer less using a cox-2 inhibitor than with a classic nonsteroidal anti-inflammatory drug?"

[Multidetector CT and MRI in diseases of the gastrointestinal tract].

Unlabelled: With the introduction of spiral scanning then multidetector technologies, the accuracy for diagnosing digestive tract diseases with CT has been highly improved, and CT is used more and more in the evaluation of patients with suspected gastrointestinal disorders. CT is able to demonstrate both the intramural and the extramural components of the disease, and has a major role in the preoperative staging and the follow-up. Improvements of CT protocols, such as CT-enteroclysis, or multiplanar 2D and 3D post-processing, including now techniques for "virtual endoscopy", lead to discuss new indications in which CT could now compete with conventional X-rays series and videoendoscopy.

[Abdominal tomometry. Application to study of the liver. Experimental study, initial clinical results and perspectives in the exploration of tumour pathology (author's transl)].

Over a period of two months, 120 patients were studied using an Acta-Scanner tomometer for various hepatic disorders. In parallel, comparative tomometric and pathological studies were carried out in cadavers and isolated livers. These made possible the recognition of normal structures in tomometry and the identification of certain hepatic images which might be potential sources of error.