Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes.

Background: Polymorphic ventricular tachycardia (PMVT) is a rare genetic disease associated with structurally normal hearts which in 8% of cases can lead to sudden cardiac death, typically exercise-induced. We previously showed a link between the RyR2-H29D mutation and a clinical phenotype of short-coupled PMVT at rest using patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs). In the present study, we evaluated the effects of clinical and experimental anti-arrhythmic drugs on the intracellular Ca handling, contractile and molecular properties in PMVT hiPSC-CMs in order to model a personalized medicine approach in vitro.

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of , , or in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L).

Constitutively Activating GNAS Somatic Mutation in Right Ventricular Outflow Tract Tachycardia.

[Figure: see text].

Cardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2.

Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples.

An Immuno-Cardiac Model for Macrophage-Mediated Inflammation in COVID-19 Hearts.

[Figure: see text].

SARS-CoV-2 Infected Cardiomyocytes Recruit Monocytes by Secreting CCL2.

Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. In order to study the cause of myocardial pathology in COVID-19 patients, we used a hamster model to determine whether following infection SARS-CoV-2, the causative agent of COVID-19, can be detected in heart tissues. Here, we clearly demonstrate that viral RNA and nucleocapsid protein is present in cardiomyocytes in the hearts of infected hamsters.

Modeling polymorphic ventricular tachycardia at rest using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

Background: While mutations in the cardiac type 2 ryanodine receptor (RyR2) have been linked to exercise-induced or catecholaminergic polymorphic ventricular tachycardia (CPVT), its association with polymorphic ventricular tachycardia (PMVT) occurring at rest is unclear. We aimed at constructing a patient-specific human-induced pluripotent stem cell (hiPSC) model of PMVT occurring at rest linked to a single point mutation in RyR2.

Methods: Blood samples were obtained from a patient with PMVT at rest due to a heterozygous RyR2-H29D mutation.

A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas.

Equivalent live-birth rate in antagonist IVF/ICSI protocol after oocyte triggering with GnRH agonist supplemented with 1500 r-hCG the day of oocyte retrieval vs r-hCG : A case-control study.

Objective: To compare live birth rate after fresh transfer and cumulative birth rates after vitrified embryo transfer in patients triggered by GnRHa, and 1500 r-hCG bolus on the day of the pick up to a selected population of patients triggered by r-hCG.

Design: Retrospective case-control study SETTING: Private hospital, Rennes, France PATIENTS: Patients with more than 18 follicles greater than 11 mm on the day of the triggering, or patients with a history of OHSS INTERVENTION: We triggered according to the European protocol by GnRHa and a bolus of 1500 UI of r-HCG on the day of the pick-up and performed if possible a fresh transfer on day 2, 3 or 5.

Main Outcome Measure: The live birth rate using fresh transfer (FT) and the cumulative birth rate by cycle of FT and frozen embryo transfer (FET) between patients triggered by GnRHa with a bolus injection of 1500 r-hCG and patients triggered by r-hCG.

Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome.

Background: More than 90% of individuals with Noonan syndrome (NS) with mutations clustered in the CR2 domain of RAF1 present with severe and often lethal hypertrophic cardiomyopathy (HCM). The signaling pathways by which NS RAF1 mutations promote HCM remain elusive, and so far, there is no known treatment for NS-associated HCM.

Methods: We used patient-derived RAF1 and CRISPR-Cas9-generated isogenic control inducible pluripotent stem cell (iPSC)-derived cardiomyocytes to model NS RAF1-associated HCM and to further delineate the molecular mechanisms underlying the disease.

Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene.

Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD Syndrome, is a rare autosomal dominant disorder. Approximately 90% of NSML cases are caused by missense mutations in the PTPN11 gene which encodes the protein tyrosine phosphatase SHP2. A human induced pluripotent stem cell (iPSC) line was generated using peripheral blood mononuclear cells (PBMCs) from a patient with NSML that carries a gene mutation of p.

A Wake-Up Call for Routine Morbidity and Mortality Review Meeting Procedures as Part of a Quality Governance Programs in Radiation Therapy Departments: Results of the PROUST Survey.

Purpose: Morbidity and mortality review (MMR) meetings in radiation therapy (RT) departments aim to monitor radiation-induced toxicities and identify potential factors that may be correlated with their development and severity, particularly treatment planning errors. The aims of the Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (PROUST) survey were to make an inventory of existing MMR procedures and to describe their procedures.

Methods And Materials: The link to the web-based questionnaire of the PROUST survey was sent to 351 radiation oncologists working at 172 centers.

RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis.

The Ras-related guanosine triphosphatase RhoA mediates pathological cardiac hypertrophy, but also promotes cell survival and is cardioprotective after ischemia/reperfusion injury. To understand how RhoA mediates these opposing roles in the myocardium, we generated mice with a cardiomyocyte-specific deletion of RhoA. Under normal conditions, the hearts from these mice showed functional, structural, and growth parameters similar to control mice.

The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease.

Congenital heart disease is the most common human developmental disorder, affecting ∼1:100 newborns, and is the primary cause of birth-defect related deaths worldwide. As a major regulator of receptor tyrosine kinase (RTK), cytokine and G-protein coupled receptor signaling, the non-receptor protein tyrosine phosphatase SHP2 plays a critical role in normal cardiac development and function. Indeed, SHP2 participates in a wide variety of cellular functions, including proliferation, survival, differentiation, migration, and cell-cell communication.

[GnRH agonist triggering in IVF and luteal phase support in women at risk of ovarian hyperstimulation syndrome].

Objective: To evaluate the efficacy and safety of ovulation triggering by agonists in antagonists IVF cycles with fresh embryo transfer in modulating low HCG dose for luteal phase support in patients at risk of ovarian hyperstimulation syndrome (OHSS).

Patients And Methods: In an observational study from September 2011 to March 2013, we triggered with agonist 107 cycles with OHSS risk, we initially triggered 39 cycles with 2 doses of Triptorelin 0.1 mg.

Sexual and functional results after creation of a neovagina in women with Mayer-Rokitansky-Küster-Hauser syndrome: a comparison of nonsurgical and surgical procedures.

Objective: To compare nonsurgical and surgical procedures for creation of a neovagina in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome in terms of sexual satisfaction.

Study Design: We report a cross-sectional study of 91 women with MRKH syndrome undergoing a neovagina creation procedure. They were members of the French National Association of Women with MRKH syndrome.

β-adrenergic receptor stimulation transactivates protease-activated receptor 1 via matrix metalloproteinase 13 in cardiac cells.

Background: Chronic β-adrenergic receptor (β-AR) overstimulation, a hallmark of heart failure, is associated with increased cardiac expression of matrix metalloproteinases (MMPs). MMP-1 has been shown to cleave and activate the protease-activated receptor 1 (PAR1) in noncardiac cells. In the present study, we hypothesized that β-AR stimulation would result in MMP-dependent PAR1 transactivation in cardiac cells.

[Quality control of dose delivered by in vivo dosimetry: can one tolerance be used for all localizations?].

Purpose: In vivo dosimetry measurements are accepted when the difference between measured and calculated dose is under 5%. A statistical analysis has been conducted to determine whether this tolerance matched the clinical practice for the studied localizations: pelvis, thorax, head and neck, breast.

Materials And Methods: The technical characteristics of the detectors were checked before being used in clinical practice.

Involvement of ITIH5, a candidate gene for congenital uterovaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome), in female genital tract development.

The ITI (inter-trypsine inhibitor) gene family includes five genes (ITIH1 to ITIH5) that encode proteins involved in the dynamics of the extracellular matrix (ECM). ITIH5 was found inactivated by partial deletion in a case of congenital uterovaginal aplasia, a human rare disease also called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The aim of the present study was to analyze the expression of ITIH5 in the uterus in adult life and during embryogenesis in order to establish the involvement of this gene in both normal and pathological conditions of uterus development.

Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease.

Tissue homeostasis requires an effective, limited wound-healing response to injury. In chronic disease, failure to regenerate parenchymal tissue leads to the replacement of lost cellular mass with a fibrotic matrix. The mechanisms that dictate the balance of cell regeneration and fibrogenesis are not well understood.

Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice.

Objective: Cyclophilin A (CyPA, encoded by Ppia) is a proinflammatory protein secreted in response to oxidative stress in mice and humans. We recently demonstrated that CyPA increased angiotensin II (Ang II)-induced reactive oxygen species (ROS) production in the aortas of apolipoprotein E (Apoe)-/- mice. In this study, we sought to evaluate the role of CyPA in Ang II-induced cardiac hypertrophy.

[Oocyte donation as in France].

Oocyte donation, initially proposed in agonadal women, saw indications expand to ovarian deficiencies and failures of in vitro fertilization (IVF), resulting in a significant increasing demand. The recruitment of oocyte donors is a critical issue for all countries that have allowed this practice. The French legislation, with the laws of bioethics, is clearly the most restrictive of European countries, imposing an absolute free gift from mother.