Identification of new correctors for traffic-defective ABCB4 variants by a high-content screening approach.

ABCB4 is located at the canalicular membrane of hepatocytes and is responsible for the secretion of phosphatidylcholine into bile. Genetic variations of this transporter are correlated with rare cholestatic liver diseases, the most severe being progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 patients most often require liver transplantation.

Management of Bleeding and Hemolysis During Percutaneous Microaxial Flow Pump Support: A Practical Approach.

Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes.

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a critical component of the kallikrein-kinin system. Its dysregulation may lead to increased vascular permeability and release of inflammatory chemokines. Interactions between the kallikrein-kinin and the coagulation system might further contribute to thromboembolic complications in COVID-19.

TrkA mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly.

Congenital hydrocephalus is a potentially devastating, highly heterogeneous condition whose genetic subset remains incompletely known. We here report a consanguineous family where three fetuses presented with brain ventriculomegaly and limb contractures and shared a very rare homozygous variant of KIDINS220, consisting of an in-frame deletion of three amino acids adjacent to the fourth transmembrane domain. Fetal brain imaging and autopsy showed major ventriculomegaly, reduced brain mass, and with no histomorphologic abnormalities.

Accidental degeneracy in the spiropyran radical cation: charge transfer between two orthogonal rings inducing ultra-efficient reactivity.

Photochromism of the spiropyran radical cation to the corresponding merocyanine form is investigated by a combination of electrochemical oxidation, UV/vis absorption spectroscopy, spectroelectrochemistry and first-principles calculations (TD-DFT, CAS-SCF and CAS-PT2). First, we demonstrate that the ring-opening of mono-spiropyrans occurs upon one-electron oxidation and that it can be driven photochemically as well as thermally, with trapping of the merocyanine by protonation. Second, in order to explain this experimentally observed spectroelectrochemical behaviour we suggest a theoretical mechanism based on the reactivity of the two lowest electronic excited-states, which promotes effective electron transfer from the indoline (nitrogen-ring) to the pyran (oxygen-ring) moieties (and vice versa) through a conical intersection seam of degeneracy.

Idarucizumab for dabigatran overdose.

Context: An overdose of oral anticoagulants represents a challenging scenario for emergency physicians. Dabigatran, an oral direct thrombin inhibitor, is increasingly used in place of warfarin. The lack of an antidote is a concern in patients who overdose on dabigatran, even though the drug can be eliminated with hemodialysis.

Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies.

Background: Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved.

Mediation by arachidonic acid metabolites of the H2O2-induced stimulation of mitogen-activated protein kinases (extracellular-signal-regulated kinase and c-Jun NH2-terminal kinase).

Reactive oxygen species modulate major cellular functions by mechanisms which are still poorly understood. Recently, H2O2 has been reported to stimulate the activity of the mitogen-activated protein kinases (MAPKs) ERK and JNK, and the expression of the proto-oncogenes c-fos and c-jun. As their expression is enhanced by H2O2 in astrocytes, we studied whether these MAPKs were stimulated by H2O2 in primary cultured astrocytes.

MET4, a leucine zipper protein, and centromere-binding factor 1 are both required for transcriptional activation of sulfur metabolism in Saccharomyces cerevisiae.

Inactivation of the centromere-binding factor 1 (CBF1) gene results in yeast strains that require methionine for growth. This auxotrophy is due to the inability of such strains to concentrate and assimilate sulfate from the medium. Northern (RNA) blot experiments reveal that the CBF1 protein is required for full induction of MET25 and MET16 gene transcription.

[Is rheumatoid arthritis connected with a digestive tract parasitosis? (author's transl)].

The comparison of blood eosinophil counts and stool parasites in two groups of patients--twenty one suffering from rheumatoid arthritis and twenty one from other various diseases--did not show any significant difference in favour of a parasitological etiology in rheumatoid arthritis, an hypothesis which had to be considered because of the efficacy of levamisole in the treatment of this disease.