ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura.

Background: Despite an increase in our understandings of pathogenesis of thrombotic thrombocytopenic purpura (TTP), the approaches for initial diagnosis and management of TTP vary significantly.

Objective: The evidence-based guidelines of the International Society on Thrombosis and Haemostasis (ISTH) are intended to support patients, clinicians, and other health care professionals in their decisions about the initial diagnosis and management of acute TTP.

Methods: In June 2018, ISTH formed a multidisciplinary panel that included hematologists, an intensive care physician, nephrologist, clinical pathologist, biostatistician, and patient representatives, as well as a methodology team from McMaster University.

Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura.

Background: Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its management.

Methods: In June 2018, the ISTH formed a multidisciplinary guideline panel to issue recommendations about treatment of TTP. The panel discussed 12 treatment questions related to both immune-mediated TTP (iTTP) and hereditary/congenital TTP (cTTP).

ISTH guidelines for treatment of thrombotic thrombocytopenic purpura.

Background: Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its appropriate treatment.

Methods: In June 2018, the ISTH formed a multidisciplinary guideline panel to issue recommendations about treatment of TTP. The panel discussed 12 treatment questions related to immune-mediated TTP (iTTP) and hereditary or congenital TTP (cTTP).

The genetics and cell biology of fertilization.

Although the general events surrounding fertilization in many species are well described, the molecular underpinnings of fertilization are still poorly understood. Caenorhabditis elegans has emerged as a powerful model system for addressing the molecular and cell biological mechanism of fertilization. A primary advantage is the ability to isolate and propagate mutants that effect gametes and no other cells.

Evidence-based use of recombinant FVIIa (NovoSeven, NiaStase) for the treatment of hemophilia with inhibitors in children and adolescents.

Children and adolescents comprise a significant proportion of the hemophilia population, including those patients who have developed inhibitors to factor VIII or FIX. We examine the use of rFVIIa for the treatment of bleeding episodes and the prevention of bleeding in children and adolescents with hemophilia A and B with inhibitors, focusing on registry data and recent clinical trial results. Based on this review of the literature, we conclude that recombinant FVIIa is safe and effective for use in controlling bleeding in these patient populations.

A comparative study of sperm morphology, cytology and activation in Caenorhabditis elegans, Caenorhabditis remanei and Caenorhabditis briggsae.

Studies of sterile mutants in Caenorhabditis elegans have uncovered new insights into fundamental aspects of gamete cell biology, development, and function at fertilization. The genome sequences of C. elegans, Caenorhabditis briggsae and Caenorhabditis remanei allow for informative comparative studies among these three species.

The genetic and molecular analysis of spe-19, a gene required for sperm activation in Caenorhabditis elegans.

During the process of spermiogenesis (sperm activation) in Caenorhabditis elegans, the dramatic morphological events that ultimately transform round sessile spermatids into polar motile spermatozoa occur without the synthesis of any new gene products. Previous studies have identified four genes (spe-8, spe-12, spe-27 and spe-29) that specifically block spermiogenesis and lead to hermaphrodite-specific fertility defects. Here, we report the cloning and characterization of a new component of the sperm activation pathway, spe-19, that is required for fertility in hermaphrodites.

Use of SNPs to determine the breakpoints of complex deficiencies, facilitating gene mapping in Caenorhabditis elegans.

Background: Genetic deletions or deficiencies have been used for gene mapping and discovery in various organisms, ranging from the nematode Caenorhabditis elegans all the way to humans. One problem with large deletions is the determination of the location of their breakpoints. This is exacerbated in the case of complex deficiencies that delete a region of the genome, while retaining some of the intervening sequence.

Molecular genetic approaches to studying fertilization in model systems.

In a wide range of experimental systems, a variety of both forward and reverse genetic approaches are becoming available for the study of the molecules involved in fertilization. An integration of these methods with the antibody-based and biochemical studies traditionally used in fertilization research is enabling rapid advancements in our understanding of this process. We highlight some of the recent advances resulting from these genetic methods and their applications in these systems.