A novel method for real-time analysis of the complement C3b:FH:FI complex reveals dominant negative variants in age-related macular degeneration.

Age-related macular degeneration (AMD) is linked to 2 main disparate genetic pathways: a chromosome 10 risk locus and the alternative pathway (AP) of complement. Rare genetic variants in complement factor H ( FH and factor I ( FI are associated with AMD. FH acts as a soluble cofactor to facilitate FI's cleavage and inactivation of the central molecule of the AP, C3b.

Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.

This review aimed to capture the key findings that animal models have provided around the role of the alternative pathway and amplification loop (AP/AL) in disease. Animal models, particularly mouse models, have been incredibly useful to define the role of complement and the alternative pathway in health and disease; for instance, the use of cobra venom factor and depletion of C3 provided the initial insight that complement was essential to generate an appropriate adaptive immune response. The development of knockout mice have further underlined the importance of the AP/AL in disease, with the FH knockout mouse paving the way for the first anti-complement drugs.

Homodimeric Minimal Factor H: Tracking and Extended Dosing Studies in Factor H Deficient Mice.

C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway (AP) of complement and treatment options remain inadequate. Factor H (FH) is a potent regulator of the AP. An in-depth analysis of FH-related protein dimerised minimal (mini)-FH constructs has recently been published.

Functional Characterization of Rare Genetic Variants in the N-Terminus of Complement Factor H in aHUS, C3G, and AMD.

Membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), atypical haemolytic uraemic syndrome (aHUS) and age-related macular degeneration (AMD) have all been strongly linked with dysfunction of the alternative pathway (AP) of complement. A significant proportion of individuals with MPGN, C3G, aHUS and AMD carry rare genetic variants in the gene that cause functional or quantitative deficiencies in the factor H (FH) protein, an important regulator of the AP. analysis of the deleteriousness of rare genetic variants in is not reliable and careful biochemical assessment remains the gold standard.

Massive Fetal Transfusion During an Emergency Ex Utero Intrapartum Treatment for a Congenital Infantile Fibrosarcoma: A Case Report.

Although originally described to assist airway management of fetal congenital malformations with life-threatening airway obstruction, the indications for an ex utero intrapartum treatment (EXIT) have expanded to include surgical resection of lesions that are potentially incompatible with life in the absence of uteroplacental circulatory support. We describe the case of an infantile fibrosarcoma (IFS) that presented with fetal hydrops and was successfully managed with an emergency EXIT that necessitated the initiation of a massive fetal blood transfusion both with and without the support of uteroplacental circulation.

Chromosomal rearrangement-A rare cause of complement factor I associated atypical haemolytic uraemic syndrome.

Chromosomal rearrangements affecting the genes encoding complement factor H and the factor H related proteins have been described in aHUS patients. To date such disorders have not been described in other aHUS associated genes. We describe here a heterozygous 875,324bp deletion encompassing the gene (CFI) encoding complement factor I and ten other genes.

A simulation-based acute skills performance assessment for anesthesia training.

Unlabelled: In an earlier study, trained raters provided reliable scores for a simulation-based anesthesia acute care skill assessment. In this study, we used this acute care skill evaluation to measure the performance of student nurse anesthetists and resident physician trainees. The performance of these trainees was analyzed to provide data about acute care skill acquisition during training.