Towards a roadmap for COSEB: the next steps in harmonization of outcomes for epidermolysis bullosa

The COSEB initiative aims for standardized and uniform measurement by developing core outcome sets for epidermolysis bullosa. This report describes the COSEB workshop organized in December 2023, which led to a broad stakeholder consensus-based roadmap. Moreover, it highlights novel features of COSEB, including the pro-active engagement of stakeholders from the very beginning and the appointment of a multi-stakeholder advisory panel

Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections

Flaviviruses are arthropod-borne viruses found worldwide and are responsible for significant human and veterinary diseases, including dengue, Zika, and West Nile fever. Some flaviviruses are insect specific and replicate only in mosquitoes. We report a genetically divergent group of insect-specific flaviviruses from Anopheles mosquitoes that do not replicate in arthropod cell lines or heterologous Anopheles species, exhibiting unprecedented specialization for their host species. Determination of the complete sequences of the RNA genomes of three of these viruses, Karumba virus (KRBV), Haslams Creek virus, and Mac Peak virus (McPV), that are found in high prevalence in some Anopheles mosquito populations and detection of virus-specific proteins, replicative double-stranded RNA, and small interfering RNA responses in the host mosquito species provided strong evidence of a functional replicating virus in the mosquito midgut. Analysis of nucleotide composition in the KRBV and McPV sequences also revealed a pattern consistent with the virus evolving to replicate only in insects. These findings represent a significant advance in our knowledge of mosquito-borne flavivirus ecology, host restriction, and evolution

Disorders of sex development: effect of molecular diagnostics

Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs

Diagnostik der taktil-kinästhetischen Wahrnehmung bei Vorschulkindern - ein Methodenvergleich

Taktil-kinästhetische Wahrnehmung TKW ist die Verarbeitung, Ordnung und Bewertung sowie die Integration von Sinneseindrücken zur Oberflächen- und Tiefensensibilität, die über spezifische Rezeptoren unterschiedlicher Lokalisation vermittelt werden. Im phoniatrisch-pädaudiologischen Umfeld ist sie insbesondere für die Sprachentwicklung bedeutsam. In dieser Studie werden zwei deutschsprachige Testverfahren zur Beurteilung der TKW, nämlich der "Diagnostische Elternfragebogen zur taktil-kinästhetischen Responsivität" DEF-TK und der "Göttinger Entwicklungstest der taktil-kinästhetischen Wahrnehmung" TAKIWA, bei 30 sprachentwicklungsgestörten Vorschulkindern verglichen. Beim DEF-TK fällt die große Zahl nicht beobachtbarer Items auf. Sie ist größer als bei den im Testmanual dargelegten Normierungsdaten, entspricht jedoch den Ergebnissen einer früheren Studie der berichtenden Arbeitsgruppe. Drei Viertel der Kinder wurden im DEF-TK als taktil-kinästhetisch auffällig eingestuft. Beim TAKIWA haben ein Viertel der Probanden Auffälligkeiten in der TKW. Der Fragebogen zur taktil-kinästhetischen Responsivität ist für eine klinische Anwendung ungeeignet, besser ist der TAKIWA-Test, dessen nosologischer und prognostischer Wert jedoch erst in weiteren Studien untersucht werden muss

Communication financière : comment tourner une obligation en source d'opportunités ?

peer reviewe

Intralysosomal hydrolysis of glycyl-L-phenylalanine 2-naphthylamide.

Glycyl-L-phenylalanine 2-naphthylamide (Gly-L-Phe-2-NNap), a cathepsin C substrate, induces an increase of the free and unsedimentable activities of this enzyme when incubated with a total mitochondrial fraction of rat liver. 1 mM-ZnSO4 considerably inhibits the cathepsin C total activity, measured with Gly-L-Phe-2-NNap as the substrate, in the presence of Triton X-100. The inhibition is markedly less pronounced when the free activity is determined; a high activity remains that depends on the integrity of the lysosomes; it decreases as the free activity of N-acetylglucosaminidase increases when lysosomes are subjected to treatments able to disrupt their membrane. Cathepsin C activity is reduced when thioethylamine hydrochloride is omitted from the incubation medium. Under these conditions at 37 degrees C, the free activity equals the total activity, although the lysosomes are intact, as indicated by the low free activity of N-acetylglucosaminidase. 1 mM-ZnSO4 strikingly inhibits the total activity, whereas more than 80% of the free activity remains. These observations are presented as evidence that Gly-L-Phe-2-NNap can possibly cause a disruption of the lysosomes as a result of its hydrolysis inside these organelles. In the presence of ZnSO4, intralysosomal hydrolysis becomes apparent, owing to a preferential inhibition by Zn2+ of extralysosomal hydrolysis; in the absence of thioethylamine hydrochloride, it is measurable because the disruption of lysosomes by Gly-L-Phe-2-NNap is delayed as a result of a slow-down of the reaction. The usefulness of Gly-L-Phe-2-NNap and related dipeptidyl naphthylamides in lysosomal-membrane-permeability studies is emphasized