Novel Insights Into Gyrate Atrophy of the Choroid and Retina (GACR): A Cohort Study.

Gyrate atrophy of the choroid and retina (GACR, OMIM #258870) is a rare inherited metabolic disorder characterized by progressive chorioretinal degeneration and hyperornithinemia. Current therapeutic modalities potentially slow disease progression but are not successful in preventing blindness. To allow for trial development, increased knowledge of the clinical phenotype and current therapeutic outcomes is required.

Initiation of Medial Calcification: Revisiting Calcium Ion Binding to Elastin.

Pathological calcification of elastin, a key connective tissue protein in the medial layers of blood vessels, starts with the binding of calcium ions. This Mini-Review focuses on understanding how calcium ions interact with elastin to initiate calcification at a molecular level, and emphasizes water's critical role in mediating this interaction. In the past decade, great strides have been made in understanding and modeling ion-specific hydration and its effects on biomolecule interactions.

Directed Assembly of Elastic Fibers via Coacervate Droplet Deposition on Electrospun Templates.

Elastic fibers provide critical elasticity to the arteries, lungs, and other organs. Elastic fiber assembly is a process where soluble tropoelastin is coacervated into liquid droplets, cross-linked, and deposited onto and into microfibrils. While much progress has been made in understanding the biology of this process, questions remain regarding the timing of interactions during assembly.

Mitochondrial ROS and base excision repair steps leading to DNA nick formation drive ultraviolet induced-NETosis.

Reactive oxygen species (ROS) is essential for neutrophil extracellular trap formation (NETosis), and generated either by NADPH oxidases (e.g., during infections) or mitochondria (e.

Maturational effect of leptin on CO chemosensitivity in newborn rats.

Background: Leptin augments central CO chemosensitivity and stabilizes breathing in adults. Premature infants have unstable breathing and low leptin levels. Leptin receptors are on CO sensitive neurons in the Nucleus Tractus Solitarius (NTS) and locus coeruleus (LC).

Ancillary radionuclide perfusion studies in the determination of death by neurologic criteria: methods, interpretation, and lexicon-a user guide for the clinician.

Radionuclide perfusion studies have an established ancillary role in determination of death by neurologic criteria (DNC). While critically important, these examinations are not well understood by individuals outside of the imaging specialties. The purpose of this review is to clarify relevant concepts and nomenclature and provide a lexicon of relevant terminology of value to non-nuclear medicine practitioners who wish to better understand these examinations.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

A tumor-suppressive function for Notch3 in the parous mammary gland.

Notch3 promotes mammary luminal cell specification and forced Notch3 activation can induce mammary tumor formation. However, recent studies suggest a tumor-suppressive role for Notch3. Here, we report on Notch3 expression and functional analysis in the mouse mammary gland.

Vascular Complications in Children Following Button Battery Ingestions: A Systematic Review.

Context: Children presenting to health care facilities with button battery (BB) impaction.

Objectives: To describe characteristics of children with vascular complications after BB impaction, as well as associated outcomes.

Data Sources: National Capital Poison Center registry and PubMed database from inception to December 2021.

Systematic profiling of the chicken gut microbiome reveals dietary supplementation with antibiotics alters expression of multiple microbial pathways with minimal impact on community structure.

Background: The emergence of antimicrobial resistance is a major threat to global health and has placed pressure on the livestock industry to eliminate the use of antibiotic growth promotants (AGPs) as feed additives. To mitigate their removal, efficacious alternatives are required. AGPs are thought to operate through modulating the gut microbiome to limit opportunities for colonization by pathogens, increase nutrient utilization, and reduce inflammation.

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit ( = 12; 98 ± 4 days; 743 ± 350 g).

Germline Biallelic Mismatch Repair Deficiency in Childhood Glioblastoma and Implications for Clinical Management.

We report a case of a 9-year-old boy with glioblastoma with a past history of colon cancer. Germline bi-allelic DNA-mismatch repair deficiency was diagnosed by a lack of immunohistochemical staining for PMS2 in the tumor and normal tissue. Family history was lacking.

Globule and fiber formation with elastin-like polypeptides: a balance of coacervation and crosslinking.

Elastic fiber assembly is a complex process that requires the coacervation and cross-linking of the protein building block tropoelastin. To date, the order, timing, and interplay of coacervation and crosslinking is not completely understood, despite a great number of advances into understanding the molecular structure and functions of the many proteins involved in elastic fiber assembly. With a simple model using elastin-like polypeptides and the natural chemical crosslinker genipin, we demonstrate the strong influence of the timing and kinetics of crosslinking reaction on the coacervation, crosslinking extent, and resulting morphology of elastin.

Performance of distinct microbial based solutions in a Campylobacter infection challenge model in poultry.

Background: Antibiotic growth promoters (AGPs) are commonly used within poultry production to improve feed conversion, bird growth, and reduce morbidity and mortality from clinical and subclinical diseases. Due to the association between AGP usage and rising antimicrobial resistance, the industry has explored new strategies including the use of probiotics and other microbial-based interventions to promote the development of a healthy microbiome in birds and mitigate against infections associated with food safety and food security. While previous studies have largely focused on the ability of probiotics to protect against Clostridium perfringens and Salmonella enterica, much less is known concerning their impact on Campylobacter jejuni, a near commensal of the chicken gut microbiome that nevertheless is a major cause of food poisoning in humans.

Single allele loss-of-function mutations select and sculpt conditional cooperative networks in breast cancer.

The most common events in breast cancer (BC) involve chromosome arm losses and gains. Here we describe identification of 1089 gene-centric common insertion sites (gCIS) from transposon-based screens in 8 mouse models of BC. Some gCIS are driver-specific, others driver non-specific, and still others associated with tumor histology.

Atlas of MRI findings of sacroiliitis in pediatric sacroiliac joints to accompany the updated preliminary OMERACT pediatric JAMRIS (Juvenile Idiopathic Arthritis MRI Score) scoring system: Part II: Structural damage lesions.

Magnetic resonance imaging (MRI) is the imaging modality of choice for identifying sacroiliitis in juvenile idiopathic arthritis (JIA). Besides active lesions of sacroiliitis, of which bone marrow edema (BME) is the key feature, structural damage lesions can also be detected. Structural changes include erosion, sclerosis, fat lesion, backfill and ankylosis, and are more common at later stages.

Atlas of MRI findings of sacroiliitis in pediatric sacroiliac joints to accompany the updated preliminary OMERACT pediatric JAMRIS (Juvenile Idiopathic Arthritis MRI Score) scoring system: Part I: Active lesions.

Magnetic resonance imaging (MRI) is an increasingly important tool for identifying involvement of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis (JIA). The key feature for diagnosing active sacroiliitis is bone marrow edema (BME), but other features of active arthritis such as joint space inflammation, inflammation in an erosion cavity, capsulitis and enthesitis can be seen as well. Structural changes may also be seen.

Machine Learning Identifies Complicated Sepsis Course and Subsequent Mortality Based on 20 Genes in Peripheral Blood Immune Cells at 24 H Post-ICU Admission.

A complicated clinical course for critically ill patients admitted to the intensive care unit (ICU) usually includes multiorgan dysfunction and subsequent death. Owing to the heterogeneity, complexity, and unpredictability of the disease progression, ICU patient care is challenging. Identifying the predictors of complicated courses and subsequent mortality at the early stages of the disease and recognizing the trajectory of the disease from the vast array of longitudinal quantitative clinical data is difficult.

The tumor cell-derived matrix of lobular breast cancer: a new vulnerability.

Invasive lobular carcinoma (ILC) of the breast is a very common disease. Despite its prevalence, these tumors are relatively understudied. One reason for this is a relative lack of models for ILC.

Progression to Metastasis of Solid Cancer.

Metastatic dissemination of cancer cells, their colonization at distal sites, and ultimate disruption of tissue physiology are the root causes of most deaths from solid cancers, particularly in tumor types where the primary lesion can be easily dissected and discarded [...

Endomembrane Tension and Trafficking.

Eukaryotic cells employ diverse uptake mechanisms depending on their specialized functions. While such mechanisms vary widely in their defining criteria: scale, molecular machinery utilized, cargo selection, and cargo destination, to name a few, they all result in the internalization of extracellular solutes and fluid into membrane-bound endosomes. Upon scission from the plasma membrane, this compartment is immediately subjected to extensive remodeling which involves tubulation and vesiculation/budding of the limiting endomembrane.