Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and a review of the first 3 years.

Purpose: Universal newborn hearing screening (UNHS) programs using audiometric techniques alone are limited in ability to detect non-congenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors: congenital cytomegalovirus (cCMV) and 22 common variants in GJB2 and SLC26A4. Here we describe our experience with genetic risk factor screening.

Disease susceptibility implications of preferential inactivation of the paternal X chromosome in extraembryonic endoderm of the mouse.

In the mouse, there is preferential inactivation of the paternally-derived X chromosome in extraembryonic tissues of early embryos, including trophectoderm and primitive endoderm or hypoblast. Although derivatives of these tissue have long been considered to be purely extraembryonic in nature, recent studies have shown that hypoblast-derived cells of the 'extraembryonic' visceral endoderm make a substantial cellular contribution to the definitive gut of the fetus. This raises questions about the eventual fate of these cells in the adult and potential disease implications due to the skewed inactivation of the paternally derived X in females heterozygous for X-linked mutations.

Interferon-gamma driven elevation of CXCL9: a new sepsis endotype independently associated with mortality.

Background: Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9.

Anti-obesity effects of Beta vulgaris and Eruca sativa-based extracts.

Obesity is a major source of morbidity worldwide with more than 2 billion adults being overweight or obese. The incidence of obesity has tripled in the last 50 years, leading to an increased risk for a variety of noncommunicable diseases. Previous studies have demonstrated the positive effects of green leafy vegetables on weight gain and obesity and have attributed these beneficial properties, at least in part, to nitrates and isothiocyanates.

Mouse embryos, chimeras, and embryonal carcinoma stem cells-Reflections on the winding road to gene manipulation.

The relationship of embryonal carcinoma (EC) cells, the stem cells of germ cell- or embryo-derived teratocarcinoma tumors, to early embryonic cells came under intense scrutiny in the early 1970s when mouse chimeras were produced between EC cells and embryos. These chimeras raised tantalizing possibilities and high hopes for different areas of research. The normalization of EC cells by the embryo lent validity to their use as in vitro models for embryogenesis and indicated that they might reveal information about the relationship between malignancy and differentiation.

Laparoscopic Ligation of the Inferior Mesenteric Artery: A Systematic Review of an Emerging Trend for Addressing Type II Endoleak Following Endovascular Aortic Aneurysm Repair.

: this systematic review aims to explore the efficacy and safety of the laparoscopic ligation of the inferior mesenteric artery (IMA) as an emerging trend for addressing a type II endoleak following endovascular aortic aneurysm repair (EVAR). : A comprehensive literature search was conducted across several databases including Medline, Scopus, and the Cochrane Central Register of Controlled Trials, adhering to the PRISMA guidelines. The search focused on articles reporting on the laparoscopic ligation of the IMA for the treatment of a type II endoleak post-EVAR.

Endovascular Coil Embolization of a Large Ruptured Splenic Artery Aneurysm: A Case Report.

This case report aims to elucidate the current practices and efficacy of endovascular repair in managing splenic artery aneurysms (SAAs), particularly focusing on a case of a large, partially ruptured SAA. A 66-year-old female presented with severe abdominal pain and was later diagnosed with a 53mm saccular, degenerative SAA showing signs of partial rupture. The patient underwent successful endovascular repair using a combination of interlocking detachable coils and fibered coils.

A Successful Endovascular Treatment of Massive Hematuria Caused by Aorto-Ureteric Fistula: A Report of a Rare Case.

Fistula formation between the urinary tract and the arterial system is very rare, and usually involves the ureter and the adjacent iliac vessels. Communication of the ureter with the aorta has been described a few times worldwide, and most of them had a fatal outcome. In our case, a 79-year-old man had a history of total cystectomy for malignancy and diversion of both ureters to a single site in the right hypogastrium with the left one crossing over the aorta.

The road to gene manipulation in the mouse: Jean Brachet Memorial Lecture of the International Society of Differentiation (delivered June 21, 2023 at Cold Spring Harbor Laboratory).

Genetic manipulation in mammals has progressed rapidly in the past decade with the advent of CRISPR-Cas gene editing tools, promising profound impacts on the understanding of human development, health and disease. However, many years of research in divergent fields of experimental embryology, genetics, reproduction, molecular biology and transgenic technology laid the groundwork and have played critical roles for this progress. This article details various threads of research and the central role of the laboratory mouse that came together in reaching this point, all from the perspective of a scientist whose research was deeply immersed in the field.

Periprosthetic Hip Joint Infection: An Uncommon Pathogen of Concern?

Background: Total hip arthroplasty is indubitably a dominant elective surgery in orthopaedics, contributing to prodigious improvement in the quality of life of patients with osteoarthritis. One of the most potentially devastating complications of this operation is periprosthetic joint infection. Immunocompromised patients might be afflicted by infrequent low-virulence organisms not typically detected with conventional procedures.

Rethinking Fluid Responsiveness during Septic Shock: Ameliorate Accuracy of Noninvasive Cardiac Output Measurements through Evaluation of Arterial Biomechanical Properties.

Beat-to-beat estimates of cardiac output from the direct measure of peripheral arterial blood pressure rely on the assumption that changes in the waveform morphology are related to changes in blood flow and vasomotor tone. However, in septic shock patients, profound changes in vascular tone occur that are not uniform across the entire arterial bed. In such cases, cardiac output estimates might be inaccurate, leading to unreliable evaluation of fluid responsiveness.

Limitation of Non-Beneficial Interventions and their Impact on the Intensive Care Unit Costs.

Introduction: Using a plan to limit non-beneficial life support interventions has significantly reduced harm and loss of dignity for patients at the end of life. The association of these limitations with patients' clinical characteristics and health care costs in the intensive care unit (ICU) needs further scientific evidence.

Aim Of The Study: To explore decisions to limit non-beneficial life support interventions, their correlation with patients' clinical data, and their effect on the cost of care in the ICU.

Mouse Gene-Targeting Strategies for Maximum Ease and Versatility.

Well-planned strategies are an essential prerequisite for any mutational analysis involving gene targeting. Consideration of the advantages or disadvantages of different methods will aid in the production of a final product that is both technically feasible and versatile. Strategies for gene-targeting experiments in the mouse are discussed, including the rationale behind some of the common elements of gene-targeting vectors, such as homologous DNA and the use of different site-specific recombinases.

Backcrossing to Generate a Congenic Mouse Strain.

Genetic background can have subtle or profound effects on mutant phenotypes, providing additional information regarding the function of the gene. If your mutation is maintained on one genetic background but you wish to analyze it on another, it is a simple matter to transfer the mutation to a recipient strain background by repeated backcrossing (introgression) as detailed in this protocol. The resulting strain is called a congenic strain, defined as a strain carrying the mutation within a segment of chromosome from the donor strain with the remainder of the genome from the recipient strain.

Phenotypic Analysis of Preimplantation Mouse Embryos in Culture.

Preimplantation embryo culture is a valuable approach to investigate a preimplantation lethal phenotype. Standard culture methods have been perfected such that the entire preimplantation period and the process of implantation can be followed in vitro. This protocol provides modifications for the analysis of clutches of embryos from heterozygous matings specifically for the purpose of distinguishing a preimplantation phenotype in homozygous mutants.

Orientation of Implanted or Dissected Mouse Embryos for Histological Sectioning.

Histological analysis is an informative part of any mutational analysis. Interpretation of histological sections is much easier, and comparisons of mutant and wild-type embryos are more reliable if the plane of sectioning is precisely controlled. This protocol provides methods for obtaining sections with reproducible orientation for embryos between E4.

Phenotypic Analysis of Preimplantation Lethality in Mice.

Preimplantation development covers a period of ∼4.5 d from fertilization to implantation in the uterus. If a homozygous mutant phenotype causes the death of embryos during this period, simple culture methods are available that support preimplantation development to allow a thorough morphological assessment.

The "No Phenotype" Challenge in Analyzing Mutant Mice.

If homozygous mutant mice survive to adulthood, are fertile, and have no visible phenotypes attributable to mutation of the relevant gene, there are a number of possible reasons why an effect of the mutation is not evident. Technical errors that might have occurred during gene targeting or genotyping must first be eliminated. Variable penetrance of the mutation should be considered as well as the possibility of age-related or late-onset phenotypes, such as tumor formation or other pathologies.

Analysis of Postnatal Mutant Phenotypes in Mice.

Viable homozygous mutant newborn mice may show effects of a mutation at any time during their development by exhibiting abnormal structure, function, or lethality. This overview guides the analysis of postnatal mice through gross anatomical assessment and the detection of visible phenotypes prior to weaning such as altered growth patterns, neurological problems, or abnormalities in movement or coordination. Advice on marking pups for identification purposes and providing adequate nutrition in the event of eating problems is given.

Phenotypic Analysis: Assessing Timing of Recessive Prenatal Lethality in Mice.

Once a recessive mutation has been established in a mouse strain in the heterozygous state, the task of phenotypic analysis of the homozygous mutants can begin. This overview leads you through a sequence of steps to determine whether the homozygous mutants are present at birth or whether the mutation causes prenatal lethality. In the case of a prenatal lethality, the time of death of the mutants, which could occur at any time during pre- or postimplanation development, must be firmly established before further phenotypic analysis.

Recovering a Targeted Mutation in Mice from Embryonic Stem Cell Chimeras or CRISPR-Cas Founders.

Following the production of chimeras from targeted embryonic stem (ES) cells or obtaining founders from CRISPR-Cas gene editing in preimplantation embryos, the desired targeted mutation must be recovered and established in the heterozygous state in a strain or stock of mice for further study. The breeding schemes for ES chimeras and CRISPR-Cas founders differ. For ES cell chimeras, we discuss the relative benefits of breeding from male or female chimeras.