Decontaminating N95 Respirators for Reuse in a Hospital Setting.

With the global outbreak of the COVID-19 pandemic, hospitals in Canada and around the world have been forced to consider conservation strategies to ensure continued availability of personal protective equipment (PPE) for healthcare providers. To mitigate critical PPE shortages, Sinai Health System (Sinai Health), a large academic healthcare institution in Canada, has developed and operationalized a standard operating procedure for the collection, decontamination and reuse of N95 respirators and other single-use PPE using a vaporized hydrogen peroxide decontamination method. Sinai Health has incorporated stringent quality assurance steps to ensure that the N95 respirators are successfully decontaminated without deformation and are safe to use.

Cage-lid hanging behavior as a translationally relevant measure of pain in mice.

The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research.

Spontaneous Bisphosphonate-related Osteonecrosis Associated with a Tooth that Had a Necrotic Pulp: A Case Report.

This study reports the endodontic treatment performed in a patient who presented with spontaneous bone exposure in the mandible while using intravenous bisphosphonate medication (Zometa , Novartis Pharmaceuticals Co., Basel, Switzerland). A 63-year-old female patient was referred to a private dental clinic at Fortaleza, Brazil.

Electrophysiological Alterations of Pyramidal Cells and Interneurons of the CA1 Region of the Hippocampus in a Novel Mouse Model of Dravet Syndrome.

Dravet syndrome is a developmental epileptic encephalopathy caused by pathogenic variation in To characterize the pathogenic substitution (p.H939R) of a local individual with Dravet syndrome, fibroblast cells from the individual were reprogrammed to pluripotent stem cells and differentiated into neurons. Sodium currents of these neurons were compared with healthy control induced neurons.

The occurrence of tarsal injuries in male mice of C57BL/6N substrains in multiple international mouse facilities.

Dislocation in hindlimb tarsals are being observed at a low, but persistent frequency in group-housed adult male mice from C57BL/6N substrains. Clinical signs included a sudden onset of mild to severe unilateral or bilateral tarsal abduction, swelling, abnormal hindlimb morphology and lameness. Contraction of digits and gait abnormalities were noted in multiple cases.

Structural Variant in Mitochondrial-Associated Gene (MRPL3) Induces Adult-Onset Neurodegeneration with Memory Impairment in the Mouse.

An impediment to the development of effective therapies for neurodegenerative disease is that available animal models do not reproduce important clinical features such as adult-onset and stereotypical patterns of progression. Using magnetic resonance imaging and behavioral testing to study male and female decrepit mice, we found a stereotypical neuroanatomical pattern of progression of the lesion along the limbic system network and an associated memory impairment. Using structural variant analysis, we identified an intronic mutation in a mitochondrial-associated gene () that is responsible for the decrepit phenotype.

Suppressor mutations in -null mice implicate the DNA damage response in Rett syndrome pathology.

Mutations in X-linked methyl-CpG-binding protein 2 ( cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in /Y mice after mutagenesis with -ethyl--nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of -null traits from screening 3177 /Y genomes.

White Matter Changes Caused by Mild Traumatic Brain Injury in Mice Evaluated Using Neurite Orientation Dispersion and Density Imaging.

Mild traumatic brain injury (mTBI) is common and can lead to persistent cognitive and behavioral symptoms. Although diffusion tensor imaging (DTI) has demonstrated some sensitivity to changes in white matter following mTBI, recent studies have suggested that more complex geometric models of diffusion, including the neurite orientation dispersion and density imaging (NODDI) model, may be more sensitive and specific. Here, we evaluate microstructural changes in white matter following mTBI using DTI and NODDI in a mouse model, and compare the time course of these changes to behavioral impairment and recovery.

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties.

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear.

Efficient Generation of Large-Fragment Knock-In Mouse Models Using 2-Cell (2C)-Homologous Recombination (HR)-CRISPR.

Generating large-fragment knock-ins, such as reporters, conditional alleles, or humanized alleles, directly in mouse embryos is still a challenging feat. We have developed 2C-HR-CRISPR, a technology that allows highly efficient (10-50%) and rapid (generating founders in 2 months) targeting of large DNA fragments. Key to this strategy is the delivery of CRISPR reagents into 2-cell-stage mouse embryos, taking advantage of the high homologous recombination activity during the long G cell cycle phase at this stage.

Generation of Large Fragment Knock-In Mouse Models by Microinjecting into 2-Cell Stage Embryos.

Large fragment knock-in mouse models such as reporters and conditional mutant mice are important models for biological research. Here we describe 2-cell (2C)-homologous recombination (HR)-CRISPR, a highly efficient method to generate large fragment knock-in mouse models by CRISPR-based genome engineering. Using this method, knock-in founders can be generated routinely in a time frame of about two months with high germline transmission efficiency.

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project.

A Comprehensive Plasma Metabolomics Dataset for a Cohort of Mouse Knockouts within the International Mouse Phenotyping Consortium.

Mouse knockouts facilitate the study ofgene functions. Often, multiple abnormal phenotypes are induced when a gene is inactivated. The International Mouse Phenotyping Consortium (IMPC) has generated thousands of mouse knockouts and catalogued their phenotype data.

A novel isoform of myosin 18A (Myo18Aγ) is an essential sarcomeric protein in mouse heart.

Whereas myosin 18B (Myo18B) is known to be a critical sarcomeric protein, the function of myosin 18A (Myo18A) is unclear, although it has been implicated in cell motility and Golgi shape. Here, we show that homozygous deletion (homozygous tm1a, tm1b, or tm1d alleles) of in mouse is embryonic lethal. Reminiscent of , was highly expressed in the embryo heart, and cardiac-restricted deletion in mice was embryonic lethal.

The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of the mammalian genome that informs conservation.

The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and phenotyping a knockout mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new mouse models of human disease have been identified thus far.

Engineering Point Mutant and Epitope-Tagged Alleles in Mice Using Cas9 RNA-Guided Nuclease.

Mice carrying patient-associated point mutations are powerful tools to define the causality of single-nucleotide variants to disease states. Epitope tags enable immuno-based studies of genes for which no antibodies are available. These alleles enable detailed and precise developmental, mechanistic, and translational research.

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes.