Monogenic diabetes in adults: A multi-ancestry study reveals strong disparities in diagnosis rates and clinical presentation.

Aim: Identification of monogenic diabetes (MgD) conveys benefits for patients' care. Algorithms for selecting the patients to be genetically tested have been established in EuroCaucasians, but not in non-EuroCaucasian individuals. We assessed the diagnosis rate, the phenotype of MgD, and the relevance of selection criteria, according to ancestry in patients referred for a suspected MgD.

Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations.

Gene panel sequencing (NGS) offers the possibility of analyzing rare forms of monogenic diabetes (MgD). To that end, 18 genes were analyzed in 1,676 patients referred for maturity-onset diabetes of the young genetic testing. Among the 307 patients with a molecular diagnosis of MgD, 55 (17.

Functional characterization of ABCC8 variants of unknown significance based on bioinformatics predictions, splicing assays, and protein analyses: Benefits for the accurate diagnosis of congenital hyperinsulinism.

ABCC8 encodes the SUR1 subunit of the β-cell ATP-sensitive potassium channel whose loss of function causes congenital hyperinsulinism (CHI). Molecular diagnosis is critical for optimal management of CHI patients. Unfortunately, assessing the impact of ABCC8 variants on RNA splicing remains very challenging as this gene is poorly expressed in leukocytes.

Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome.

Background & Aims: Approximately 75% of patients with suspected Lynch syndrome carry variants in MLH1 or MSH2, proteins encoded by these genes are required for DNA mismatch repair (MMR). However, 30% of these are variants of unknown significance (VUS). A assay that measures cell response to the cytotoxic effects of a methylating agent can determine the effects of VUS in MMR genes and identify patients with constitutional MMR-deficiency syndrome.

Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation.

HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation.

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin.

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.

Sensing with Advanced Computing Technology: Fin Field-Effect Transistors with High-k Gate Stack on Bulk Silicon.

Field-effect transistors (FETs) form an established technology for sensing applications. However, recent advancements and use of high-performance multigate metal-oxide semiconductor FETs (double-gate, FinFET, trigate, gate-all-around) in computing technology, instead of bulk MOSFETs, raise new opportunities and questions about the most suitable device architectures for sensing integrated circuits. In this work, we propose pH and ion sensors exploiting FinFETs fabricated on bulk silicon by a fully CMOS compatible approach, as an alternative to the widely investigated silicon nanowires on silicon-on-insulator substrates.

Diagnosis of community-acquired acute respiratory illness: From conventional microbiological methods to molecular detection (multiplex).

Investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. In a routine care setting, we assessed the diagnostic performance of a multiplex PCR assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. We enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at Tours University Hospital during the winter of 2011-2012.

Evaluation of a novel series of fluorine-18-labeled imidazobenzodiazepines as potential new positron emission tomography radioligands for the GABAA receptor.

Introduction: [(11)C]Flumazenil has been used to study the GABAA receptor in many preclinical and clinical studies, but the short half-life of carbon-11 means that this molecule is restricted to use by investigators with access to on-site cyclotron and radiosynthesis facilities. The radiosynthesis of [(18)F]flumazenil has been evaluated by several groups, but the radiochemical yield can be low and inconsistent. We previously reported a series of fluorine-18-labeled imidazobenzodiazepine-based ligands for the GABAA receptor, which had significantly improved radiosynthesis yields.

The development of potential new fluorine-18 labelled radiotracers for imaging the GABA(A) receptor.

Positron emission tomography (PET) using the tracer [(11)C]Flumazenil has shown changes in the distribution and expression of the GABA(A) receptor in a range of neurological conditions and injury states. We aim to develop a fluorine-18 labelled PET agent with comparable properties to [(11)C]Flumazenil. In this study we make a direct comparison between the currently known fluorine-18 labelled GABA(A) radiotracers and novel imidazobenzodiazepine ligands.

Life-threatening Escherichia coli cellulitis in patients with haematological malignancies.

Cellulitis due to Escherichia coli is rare and usually secondary to a cutaneous portal of entry. Skin and soft tissue infections (SSTI) secondary to E. coli bacteraemia have been reported exclusively in immunodeficient patients.

Synthesis of the positron-emitting radiotracer [(18)F]-2-fluoro-2-deoxy-D-glucose from resin-bound perfluoroalkylsulfonates.

A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [(19/18)F]-) is described, which employs supported perfluoroalkylsulfonate precursors , where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [(19)F]fluoride ion afforded protected FDG [(19)F]- as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [(19)F]- was shown to produce [(19)F]FDG.

EXAFS characterization of oxaliplatin anticancer drug and its degradation in chloride media.

Oxaliplatin is a second-generation platinum-based anticancer drug. Its degradation is studied in solution, in the presence of chloride ions (in neutral or acidic media) in excess. In both cases the degradation product precipitates immediately.

EXAFS and IR structural study of platinum-based anticancer drugs' degradation by diethyl dithiocarbamate.

Platinum compounds constitute a discrete class of DNA-damaging anticancer drug agents, including cisplatin, carboplatin, and oxaliplatin. The toxicity of such drugs raises the problem of waste detoxification. Diethyl dithiocarbamate (DDTC) is recommended by the World Heath Organization (WHO) for the destruction of cisplatin, but the degradation product has not been structurally characterized.

Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS.

The stability of carboplatin and oxaliplatin aqueous solutions has been studied under different chloride ions concentration and pH conditions. For both compounds, we demonstrate the chloration of the platinum first coordination shell.

Short stereoselective route to gamma-CF3 allylic alcohols: rearrangements with creation of quaternary CF3-substituted carbons.

A concise preparation of tetrasubstituted hindered functionalized CF3-olefins 2-7 from corresponding enol ether 3 is described. Geometrically pure gamma-CF3, gamma-alkyl allylic alcohols thus prepared could undergo Claisen-type rearrangements and provide, in good yields, carboxylic esters and amides containing a beta- quaternary CF3-substituted carbon.

Microwave-Promoted Lipase-Catalyzed Reactions. Resolution of (+/-)-1-Phenylethanol.

Microwave irradiation increased enzymatic affinity and selectivity of supported lipases in esterification and transesterification reactions carried out in dry media and at temperature near 100 degrees C.

[Reading and speaking].

Reading is an activity that refers to the universe of language and speech and because of this, it cannot be grasped without the existence of a speaking subject. Children must get their share of fairy tales and stories in order to live in the warmth of words and light of literature.

The kinetics of intestinal calcium absorption in the rat: an analytical and model building study.

The experimental data obtained from in vivo single pass perfusion of duodenal, jejunal, and ileal intestinal segments of 33- and 50-day-old rats have been used to test a series of models for calcium absorption. Each model was checked for the statistical validity and goodness-of-fit with the experimental data. The model adopted for the duodenum and jejunum had two major components, one saturable and the other nonsaturable, and a minor secretory component.