Paternal aging impacts expression and epigenetic markers as early as the first embryonic tissue lineage differentiation.

Background: Advanced paternal age (APA) is associated with adverse outcomes to offspring health, including increased risk for neurodevelopmental disorders. The aim of this study was to investigate the methylome and transcriptome of the first two early embryonic tissue lineages, the inner cell mass (ICM) and the trophectoderm (TE), from human blastocysts in association with paternal age and disease risk. High quality human blastocysts were donated with patient consent from donor oocyte IVF cycles from either APA (≥ 50 years) or young fathers.

Identifying risk variants for embryo aneuploidy using ultra-low coverage whole-genome sequencing from preimplantation genetic testing.

Aneuploidy frequently arises during human meiosis and is the primary cause of early miscarriage and in vitro fertilization (IVF) failure. Individuals undergoing IVF exhibit significant variability in aneuploidy rates, although the exact genetic causes of the variability in aneuploid egg production remain unclear. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing is a standard test for identifying and selecting IVF-derived euploid embryos.

Physical Restraint Use in the Pediatric Emergency Department.

Children and adolescents can present to the emergency department with acute agitation and aggression due to various physical and/or mental health conditions. With acute agitation/aggression, these patients may present a risk of injury to themselves, their caregivers, or emergency department providers/staff. It is imperative for providers to understand how to safely care for these children.

Identifying risk genes for embryo aneuploidy using ultra-low coverage whole-genome sequencing.

Background: Aneuploidy, the state of a cell containing extra or missing chromosomes, frequently arises during human meiosis and is the primary cause of early miscarriage and maternal age-related in vitro fertilization (IVF) failure. IVF patients exhibit significant variability in aneuploidy rates, although the exact genetic causes of the variability in aneuploid egg production remain unclear. Preimplantation genetic testing for aneuploidy (PGT-A) using ultra-low coverage whole-genome sequencing (ulc-WGS) is a standard test for identifying and selecting IVF-derived embryos with a normal chromosome complement.

Segmental aneuploid hotspots identified across the genome concordant on reanalysis.

The aim of this study was to characterize a large set of full segmental aneuploidies identified in trophectoderm (TE) biopsies and evaluate concordance in human blastocysts. Full segmental aneuploid errors were identified in TE biopsies (n = 2766) from preimplantation genetic testing for aneuploid (PGT-A) cycles. Full segmental deletions (n = 1872; 66.

Spatially resolved transcriptomic profiling of ovarian aging in mice.

Ovarian aging precedes that of any other mammalian organ and is the primary cause of female age-related infertility. The biological mechanisms responsible for ovarian aging remain unclear. Previous studies have been limited by their use of bulk RNA-sequencing, which masks the dynamic and heterogeneous nature of the ovary.

Liquid chromatography-tandem mass spectrometry reveals an active response to DNA damage in human spermatozoa.

Objective: To investigate how endogenously elevated DNA fragmentation alters the human sperm proteome, and whether this fragmentation contributes to genomic deletions.

Design: Research study.

Setting: Commercial fertility clinic.

Forecasting early onset diminished ovarian reserve for young reproductive age women.

Purpose: To investigate the biological networks associated with DOR in young women and the subsequent molecular impact on preimplantation embryos.

Methods: Whole peripheral blood was collected from patients: young women presenting with diminished ovarian reserve (DOR) and age-matched young women with normal ovarian reserve. Maternal exome sequencing was performed on the NovaSEQ 6000 and sequencing validation was completed using Taqman® SNP Genotyping Assays.

The prolonged disease state of infertility is associated with embryonic epigenetic dysregulation.

Objective: To evaluate the epigenetic consequence of a prolonged disease state of infertility in euploid blastocysts.

Design: Methylome analysis as well as targeted imprinted methylation and expression analysis on individual human euploid blastocysts examined in association with duration of patient infertility and time to live birth.

Setting: Research study.

The inherited methylome landscape is directly altered with paternal aging and associated with offspring neurodevelopmental disorders.

Paternal aging and the prevalence of neurodevelopmental disorders in offspring are well documented. Yet, the underlying mechanism and the mode of inheritance have not been conclusively established. Advancing paternal age is a subtle and varying phenotype.

Transcriptome signature of ventricular arrhythmia in dilated cardiomyopathy reveals increased fibrosis and activated TP53.

Aims: One-third of DCM patients experience ventricular tachycardia (VT), but a clear biological basis for this has not been established. The purpose of this study was to identify transcriptome signatures and enriched pathways in the hearts of dilated cardiomyopathy (DCM) patients with VT.

Methods And Results: We used RNA-sequencing in explanted heart tissue from 49 samples: 19 DCM patients with VT, 16 DCM patients without VT, and 14 non-failing controls.

The Giant Protein Titin's Role in Cardiomyopathy: Genetic, Transcriptional, and Post-translational Modifications of TTN and Their Contribution to Cardiac Disease.

Unlabelled: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, sudden cardiac death and heart transplant. DCM is inherited in approximately 50% of cases, in which the most frequent genetic defects are truncation variants of the titin gene (tv). encodes titin, which is the largest protein in the body and is an essential component of the sarcomere.

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy.

Background: Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood.

Objectives: The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients.

Methods: A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups.