Design and synthesis of cyclic lipidated peptides derived from the C-terminus of Cx43 for hemichannel inhibition and cardiac endothelium targeting.

A peptide segment that is 10 residues long at the C-terminal (CT) region of Cx43 is known to be involved in interactions, both with the Cx43 protein itself and with other proteins, that result in hemichannel (HC) activity regulation. Previously reported mimetic peptides based on this region (, , ) have been revealed to be promising therapeutic agents in the context of cardiovascular diseases. In this work, novel approaches, such as C- and N-terminal modification and cyclization, to improve the proteolytic stability and bioavailability of the peptide are presented.

Health mediation does not reduce the readmission rate of frequent users of emergency departments living in precarious conditions: what lessons can be learned from this randomised controlled trial?

Background: Severe overcrowding of emergency departments (EDs) affects the quality of healthcare. One factor of overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare.

Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design.

Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with and . These peptides differ from by substituting His with Pro and inserting Gly or Arg.

Structure-Based Design and Synthesis of Stapled Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases.

Following a rational design, a series of macrocyclic ("stapled") peptidomimetics of Panx1, the most established peptide inhibitor of Pannexin1 (Panx1) channels, were developed and synthesized. Two macrocyclic analogues and outperformed the linear native peptide. During adenosine triphosphate (ATP) release and Yo-Pro-1 uptake assays in a Panx1-expressing tumor cell line, both compounds were revealed to be promising bidirectional inhibitors of Panx1 channel function, able to induce a two-fold inhibition, as compared to the native Panx1 sequence.

Hypochondroplasia gain-of-function mutation in FGFR3 causes defective bone mineralization in mice.

Hypochondroplasia (HCH) is a mild dwarfism caused by missense mutations in fibroblast growth factor receptor 3 (FGFR3), with the majority of cases resulting from a heterozygous p.Asn540Lys gain-of-function mutation. Here, we report the generation and characterization of the first mouse model (Fgfr3Asn534Lys/+) of HCH to our knowledge.

Determination of structural features that underpin the pannexin1 channel inhibitory activity of the peptide Panx1.

Pannexin1 channels facilitate paracrine communication and are involved in a broad spectrum of diseases. Attempts to find appropriate pannexin1 channel inhibitors that showcase target-selective properties and in vivo applicability remain nonetheless scarce. However, a promising lead candidate, the ten amino acid long peptide mimetic Panx1 (H-Trp-Arg-Gln-Ala-Ala-Phe-Val-Asp-Ser-Tyr-OH), has shown potential as a pannexin1 channel inhibitor in both in vitro and in vivo studies.

Health mediation: an intervention mode for improving emergency department care and support for patients living in precarious conditions.

Background: Severe overcrowding of emergency departments (EDs) impacts the quality of healthcare. One factor of this overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare.

Less-invasive autopsy for early pregnancy loss.

Autopsy investigations provide valuable information regarding fetal death that can assist in the parental bereavement process, and influence future pregnancies, but conventional autopsy is often declined by parents because of its invasive approach. This has led to the development of less-invasive autopsy investigations based on imaging technology to provide a more accessible and acceptable choice for parents when investigating their loss. Whilst the development and use of more conventional clinical imaging techniques (radiographs, CT, MRI, US) are well described in the literature for fetuses over 20 weeks of gestational age, these investigations have limited diagnostic accuracy in imaging smaller fetuses.

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels.

Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections.

Explicit and automatic ejection fraction assessment on 2D cardiac ultrasound with a deep learning-based approach.

Background: Ejection fraction (EF) is a key parameter for assessing cardiovascular functions in cardiac ultrasound, but its manual assessment is time-consuming and subject to high inter and intra-observer variability. Deep learning-based methods have the potential to perform accurate fully automatic EF predictions but suffer from a lack of explainability and interpretability. This study proposes a fully automatic method to reliably and explicitly evaluate the biplane left ventricular EF on 2D echocardiography following the recommended modified Simpson's rule.

Extending the prenatal Noonan's phenotype by review of ultrasound and autopsy data.

Objectives: The antenatal phenotypic spectrum of Noonan Syndrome (NS) requires better characterization.

Methods: This multicenter retrospective observational included 16 fetuses with molecularly confirmed NS admitted for fetopathological examination between 2009 and 2016.

Results: Among 12 pathogenic variants (PV) in PTPN11 (80%), 5 (42%) fell between position c.

Impact of a health literacy intervention combining general practitioner training and a consumer facing intervention to improve colorectal cancer screening in underserved areas: protocol for a multicentric cluster randomized controlled trial.

Background: Colorectal cancer (CRC) is a leading cause of cancer burden worldwide. In France, it is the second most common cause of cancer death after lung cancer. Systematic uptake of CRC screening can improve survival rates.

Beta and Theta Oscillations Correlate With Subjective Time During Musical Improvisation in Ecological and Controlled Settings: A Single Subject Study.

In this paper, we describe the results of a single subject study attempting at a better understanding of the subjective mental state during musical improvisation. In a first experiment, we setup an ecological paradigm measuring EEG on a musician in free improvised concerts with an audience, followed by retrospective rating of the mental state of the improviser. We introduce Subjective Temporal Resolution (STR), a retrospective rating assessing the instantaneous quantization of subjective timing of the improviser.

Structure-Based Design of Melanocortin 4 Receptor Ligands Based on the SHU-9119-hMC4R Cocrystal Structure†.

The melanocortin receptors (MC1R-MC5R) belong to class A G-protein-coupled receptors (GPCRs) and are known to have receptor-specific roles in normal and diseased states. Selectivity for MC4R is of particular interest due to its involvement in various metabolic disorders, including obesity, feeding regulation, and sexual dysfunctions. To further improve the potency and selectivity of MC4R (ant)agonist peptide ligands, we designed and synthesized a series of cyclic peptides based on the recent crystal structure of MC4R in complex with the well-characterized antagonist (Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH).

[Training simulation during the announcement of fetal malformation discovered on screening ultrasound: Results of a pilot study].

Objectives: Breaking bad news (BBN) to a pregnant woman with fetal abnormalities (FA) on ultrasound (US) examination is a challenge. Announcement technique influences patient reaction. Physicians receive little training in BBN.

Evidence for and against vertical transmission for severe acute respiratory syndrome coronavirus 2.

COVID-19 can severely affect pregnant women Furthermore, issues regarding vertical transmission of severe acute respiratory syndrome coronavirus 2 are emerging. In patients and neonates who are showing symptoms of coronavirus disease 2019, real-time polymerase chain reaction of nasal and throat swabs, sputum, and feces is performed to detect the presence of severe acute respiratory syndrome coronavirus 2. In addition, real-time polymerase chain reaction of vaginal swabs, amniotic fluid, placenta, cord blood, neonatal blood, or breast milk for the detection of severe acute respiratory syndrome coronavirus 2 did not show substantial results.

Early needle aspiration of large infant cephalohematoma: a safe procedure to avoid esthetic complications.

Cephalohematoma is a common pathology in newborns. Observation is the primary treatment for most patients with small uncomplicated cephalohematoma. Conversely, a large cephalohematoma can lead to calcification with unesthetic local deformation or deformational plagiocephaly.

Three-dimensional computer-assisted dissection of pancreatic lymphatic anatomy on human fetuses: a step toward automatic image alignment.

Purpose: Pancreatic cancer is the fourth cause of death by cancer worldwide. Lymph node (LN) involvement is known to be the main prognostic factor. However, lymphatic anatomy is complex and only partially characterized.

Controlling Dipole Orientation through Curvature: Aromatic Foldamer Bent β-Sheets and Helix-Sheet-Helix Architectures.

The helix, turn, and β-strand motifs of biopolymer folded structures have been found to prevail also in non-natural backbones. In contrast, foldamers with aryl rings in their main chains possess distinct conformations that may give access to folded objects beyond the reach of peptidic and nucleotidic backbones. In search of such original architectures, we have explored the effect of bending aromatic amide β-sheets using building blocks that impart curvature.

[Absent or hypoplastic thymus: A marker for 22q11.2 microdeletion syndrome in case of polyhydramnios].

Objectives: In prenatal diagnosis of 22q11.2 microdeletion syndrome, without cardiac malformation or multiple associated congenital anomalies, we study the presence of polyhydramnios and its association with thymic dysgenesis.

Materials And Methods: This was a multicenter retrospective observational study.