Creation of the Indigenous Support Line for health system navigation and culturally safe access to care: a quality improvement project.

Indigenous Peoples face inequities in health and healthcare access due to colonial history and systems. To work towards the Truth and Reconciliation Commission of Canada's Calls to Action and the United Nations Declaration on the Rights of Indigenous Peoples, Alberta Health Services has collaborated with a Wisdom Council of engaged Elders and Indigenous community members to tailor programmes for Indigenous Peoples. The Indigenous Support Line (ISL) was created based on the Wisdom Council's advice to provide an Indigenous-specific concerns line, which later expanded into a telehealth line to address any health questions or access issues, including health system navigation and access to Western and Indigenous health and wellness supports.

Impaired mitochondrial morphological plasticity and failure of mitophagy associated with the G11778A mutation of LHON.

Mitochondrial dynamics were examined in human dermal fibroblasts biopsied from a confirmed Leber's Hereditary Optic Neuropathy (LHON) patient with a homoplasmic G11778A mutation of the mitochondrial genome. Expression of the G11778A mutation did not impart any discernible difference in mitochondrial network morphology using widefield fluorescence microscopy. However, at the ultrastructural level, cells expressing this mutation exhibited an impairment of mitochondrial morphological plasticity when forced to utilize oxidative phosphorylation (OXPHOS) by transition to glucose-free, galactose-containing media.

Galactose-replacement unmasks the biochemical consequences of the G11778A mitochondrial DNA mutation of LHON in patient-derived fibroblasts.

Leber's hereditary optic neuropathy (LHON) is a visual impairment associated with mutations of mitochondrial genes encoding elements of the electron transport chain. While much is known about the genetics of LHON, the cellular pathophysiology leading to retinal ganglion cell degeneration and subsequent vision loss is poorly understood. The impacts of the G11778A mutation of LHON on bioenergetics, redox balance and cell proliferation were examined in patient-derived fibroblasts.

Hybrid RPA:DFT Approach for Adsorption on Transition Metal Surfaces: Methane and Ethane on Platinum (111).

The hybrid QM:QM approach is extended to adsorption on transition metal surfaces. The random phase approximation (RPA) as the high-level method is applied to cluster models and, using the subtractive scheme, embedded in periodic models which are treated with density functional theory (DFT) that is the low-level method. The PBE functional, both without dispersion and augmented with the many-body dispersion (MBD), is employed.

Effects of TP63 mutations on keratinocyte adhesion and migration.

The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools.

Neutralizing Antibody Validation Testing and Reporting Harmonization.

Evolving immunogenicity assay performance expectations and a lack of harmonized neutralizing antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. A team of experts within the American Association of Pharmaceutical Scientists' Therapeutic Product Immunogenicity Community across industry and the Food and Drug Administration addressed challenges unique to cell-based and non-cell-based neutralizing antibody assays. Harmonization of validation expectations and data reporting will facilitate filings to health authorities and are described in this manuscript.

Reoperative Anorectal Procedures in Patients with Anorectal Malformations - Is Bladder Function Affected?

Background: Anorectal malformations (ARM) are associated with neurogenic bladder. The traditional surgical ARM repair is a posterior sagittal anorectoplasty (PSARP), which is believed to have a minimal effect on bladder dynamics. However, little is known about the effects of reoperative PSARP (rPSARP) on bladder function.

Effects of TP63 Mutations on Keratinocyte Adhesion and Migration.

The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools.

Effects of acetazolamide on linear growth in children with pseudotumor cerebri syndrome.

Background/introduction: While oral acetazolamide is a cornerstone of management of adult and pediatric PTCS, previous studies have suggested that acetazolamide used in children with other conditions may influence growth.

Aims And Methods: Retrospective chart review involving a single tertiary medical center. Thirty-four children with definite or probable PTCS were identified.

Myh6 promoter-driven Cre recombinase excises floxed DNA fragments in a subset of male germline cells.

Myh6-Cre transgenic mouse line was known to express Cre recombinase only in the heart. Nevertheless, during breeding Myh6-Cre to Rosa26 reporter (tdTom) mouse line, we observed that a significant part of their F2 tdTom/+ offspring had tdTom reporter gene universally activated. Our results show that Myh6-Cre transgenic mice have Cre recombinase activity in a subpopulation of the male germline cells, and that Myh6 gene transcripts are enriched in the interstitial Leydig cells and the undifferentiated spermatogonia stem cells.

Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development.

Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo-YAP pathway, YAP and TEAD1 form a transcriptional complex that regulates the target gene expression and depletes either of these two genes in cardiomyocytes, thus resulting in cardiac hypoplasia. Vestigial-like 4 (VGLL4) is a transcriptional co-factor that interacts with TEAD and suppresses the YAP/TEAD complex by competing against YAP for TEAD binding.

Leber Hereditary Optic Neuropathy in Southwestern Ontario: A Growing List of Mutations.

Background: Leber hereditary optic neuropathy (LHON) is a rare but bilaterally blinding disease. Three characteristic disease-causing point mutations, and other less common mutations, are most often found on the mitochondrially encoded genes of NADH-ubiquinone oxidoreductase core subunits (MT-ND). The purpose of this study is to provide an overview of LHON mutations in Southwestern Ontario and to describe the associated demographic and clinical characteristics.

Recommendations on ELISpot assay validation by the GCC.

Gene therapy, cell therapy and vaccine research have led to an increased need to perform cellular immunity testing in a regulated environment to ensure the safety and efficacy of these treatments. The most common method for the measurement of cellular immunity has been Enzyme-Linked Immunospot assays. However, there is a lack of regulatory guidance available discussing the recommendations for developing and validating these types of assays.

Adsorption of CH on the Pt(111) surface: Random phase approximation compared to density functional theory.

We investigate the adsorption of CH on the Pt(111) surface for two adsorption modes, hcp (hexagonal closed packed) hollow tripod and top monopod in a (√3 × √3)R30° surface cell that corresponds to experimental surface coverage. Surface structures are optimized with density functional theory using the Perdew-Burke-Ernzerhof (PBE) functional augmented with the many-body dispersion scheme of Tkatchenko (PBE+MBD). Whereas the Random Phase Approximation (RPA) predicts a clear preference of about 5 kJ mol for the hcp tripod compared to the top monopod structure, in agreement with vibrational spectra, PBE+MBD predicts about equal stability for the two adsorption structures.

Quantitative Optical Coherence Tomography Angiography in Patients with Moyamoya Vasculopathy: A Pilot Study.

Moyamoya (MM) disease is a chronic cerebrovascular disease that can lead to progressive stenosis of the terminal portions of the internal carotid arteries and their proximal branches. We sought to investigate and quantify retinal vascular changes in patients with MM vasculopathy (MMV) using optical coherence tomography angiography (OCTA) compared to healthy controls. Our findings reveal retinal microvascular changes in patients with MMV and highlights the potential of OCTA imaging for the detection of subclinical retinal pathology.

Autism Spectrum Disorder in Pediatric Idiopathic Intracranial Hypertension.

In recent years, the substantial burden of medical comorbidities in autism spectrum disorder (ASD) populations has been described. We report a retrospective observational case series of pediatric patients with suspected idiopathic intracranial hypertension (IIH) and concurrent ASD. Pediatric subjects with suspected IIH aged 2-18 years were identified by review of a pediatric neuro-ophthalmologist's database spanning from July 1993 to April 2013.

Corpus callosum lesions are not inextricably linked to CNS symptoms in reported cases of susac syndrome.

Objective: To evaluate whether corpus callosum (CC) lesions are inextricably linked to CNS symptoms of Susac Syndrome (SuS) by reviewing published cases to find instances where: 1) CC lesions occur without CNS symptoms, and 2) whether patients with CNS symptoms lack CC lesions.

Methods: 100 reported cases of SuS were identified in PubMed. Clinical symptoms, para-clinical testing and MRI data were collected both at presentation and for any available follow-up and analyzed.

INVESTIGATING MICROANGIOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH SUSAC SYNDROME.

Purpose: To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes.

Methods: We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system.

Culture-independent multilocus sequence typing of Pseudomonas aeruginosa for cross-infection screening.

The genotyping of pathogens within cystic fibrosis cohorts is an important process, enabling the detection of transmissible and clinically-important strains. Traditionally this has been via culture-dependent processes. However, culture-independent investigation of respiratory samples is becoming more common, with such approaches highlighting the limitations of culture-based methods.

Is There an Association between Herpetic Infections and Giant Cell Arteritis? A Population-Based Study.

Recent data suggests that herpes zoster (HZ) and herpes simplex virus (HSV) may be one of the underlying immunological triggers for giant cell arteritis (GCA). However, there is limited population-based data to support this. Our goal was to determine if herpetic infections increase the likelihood of GCA in the British Columbia (BC) population.

Outcomes according to channel type for continent catheterizable channels in patients undergoing simultaneous urinary and fecal reconstruction.

Introduction: When creating a continent catheterizable channel (CCC) the choice of bowel segment used as the conduit should be tempered with the morbidity associated with it. The split-appendix technique allows the creation of both a urinary and fecal CCC without the need for a bowel anastomosis. However, there is concern that by splitting the appendix there is compromise to its blood supply and may affect outcomes.

Ion-molecule interactions enable unexpected phase transitions in organic-inorganic aerosol.

Atmospheric aerosol particles are commonly complex, aqueous organic-inorganic mixtures, and accurately predicting the properties of these particles is essential for air quality and climate projections. The prevailing assumption is that aqueous organic-inorganic aerosols exist predominately with liquid properties and that the hygroscopic inorganic fraction lowers aerosol viscosity relative to the organic fraction alone. Here, in contrast to those assumptions, we demonstrate that increasing inorganic fraction can increase aerosol viscosity (relative to predictions) and enable a humidity-dependent gel phase transition through cooperative ion-molecule interactions that give rise to long-range networks of atmospherically relevant low-mass oxygenated organic molecules (180 to 310 Da) and divalent inorganic ions.

Pseudotumor cerebri syndrome with different types of hormonal contraceptives in women of child-bearing age.

Background And Purpose: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel.

Methods: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA.