Assessment of Aminoglycoside-Induced Hearing Loss Risk in the Perinatal Period.

Objective:  This study aimed to determine the prevalence and heteroplasmy level(s) of variants m.1555A > G and m.1494C > T, which are associated with aminoglycoside-induced hearing loss, in a general perinatal population.

A Practical Guide to Whole Genome Sequencing in the NICU.

The neonatal period is a peak time for the presentation of genetic disorders that can be diagnosed using whole genome sequencing (WGS). While any one genetic disorder is individually rare, they collectively contribute to significant morbidity, mortality, and health-care costs. As the cost of WGS continues to decline and becomes increasingly available, the ordering of rapid WGS for NICU patients with signs or symptoms of an underlying genetic condition is now feasible.

Neonatal hemophagocytic lymphohistiocytosis: A meta-analysis of 205 cases.

Background: Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH.

Objectives: The objective of this study was to perform a meta-analysis of published cases of nHLH.

State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies.

There is a broad phenotypic spectrum of monogenic polycystic kidney diseases (PKDs). These disorders often involve cilia-related genes and lead to the development of fluid-filled cysts and eventual kidney function decline and failure. Preimplantation genetic testing for monogenic (PGT-M) disorders has moved into the clinical realm.

Neonatal Diagnosis of Alveolar Capillary Dysplasia via Rapid Genomic Sequencing: A New Gold Standard?

Classic alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare congenital lung disorder presenting in the early neonatal period with refractory hypoxemic respiratory failure and pulmonary hypertension. No curative treatment is currently available. Although definitive diagnosis is obtained by histology, lung biopsy is often challenging in unstable, critically ill neonates.

Activation of homology-directed DNA repair plays key role in CRISPR-mediated genome correction.

Gene editing for the cure of inborn errors of metabolism (IEMs) has been limited by inefficiency of adult hepatocyte targeting. Here, we demonstrate that in utero CRISPR/Cas9-mediated gene editing in a mouse model of hereditary tyrosinemia type 1 provides stable cure of the disease. Following this, we performed an extensive gene expression analysis to explore the inherent characteristics of fetal/neonatal hepatocytes that make them more susceptible to efficient gene editing than adult hepatocytes.

The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.

Introduction: Inborn errors of metabolism (IEMs) often result from single-gene mutations and collectively cause liver dysfunction in neonates leading to chronic liver and systemic disease. Current treatments for many IEMs are limited to maintenance therapies that may still require orthotropic liver transplantation. Gene therapies offer a potentially superior approach by correcting or replacing defective genes with functional isoforms; however, they face unique challenges from complexities presented by individual diseases and their diverse etiology, presentation, and pathophysiology.

Personalized Video Feedback and Repeated Task Practice Improve Laparoscopic Knot-Tying Skills: Two Controlled Trials.

Purpose: Compare the effect of personalized feedback (PF) vs. task demonstration (TD), both delivered via video, on laparoscopic knot-tying skills and perceived workload; and evaluate the effect of repeated practice.

Method: General surgery interns and research fellows completed four repetitions of a simulated laparoscopic knot-tying task at one-month intervals.

Cells with Treg-specific FOXP3 demethylation but low CD25 are prevalent in autoimmunity.

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3 cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3 cells within CD127CD25 CD4 T cells (here defined as CD25FOXP3 T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes.

IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.

Aims/hypothesis: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes.

Methods: We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors.

Meiotic recombination between paralogous RBCSB genes on sister chromatids of Arabidopsis thaliana.

Paralogous genes organized as a gene cluster can rapidly evolve by recombination between misaligned paralogs during meiosis, leading to duplications, deletions, and novel chimeric genes. To model unequal recombination within a specific gene cluster, we utilized a synthetic RBCSB gene cluster to isolate recombinant chimeric genes resulting from meiotic recombination between paralogous genes on sister chromatids. Several F1 populations hemizygous for the synthRBCSB1 gene cluster gave rise to Luc+ F2 plants at frequencies ranging from 1 to 3 x 10(-6).