RASopathies: unraveling mechanisms with animal models

RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births) motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment

The ROM / UWO Mummy Project: A Microcosm of Progress in Mummy Research

The beginnings of the Royal Ontario Museum can be traced back to the excavations and collections of Charles Trick Currelly, a staff member of the Egyptian Exploration Fund in the early 1900s. Currelly excavated with Sir Flinders Petrie at Abydos and with Edouard Naville at Deir el Bahari. With the assistance of Robert Mond and others, Currelly amassed a rich and diverse collection that became the basis for the ROM, which opened its doors in 1914. Part of that collection included several Egyptian mummies (Currelly 1971) . The Egyptologicalholdings at the ROM include eight mummies: one dating to the Predynastic Period, five from the Pharaonic Period, one from the Roman Period and one without context. Two of these, Nakht and Djedmaatesankh, have been well studied by Peter Lewin and associates, while three more are the subjects of the current investigation. The objectives of this poster are to review the work and accomplishments of the previous research, to describe the preliminary results of the current research project and to outline directions for future work

The UQAM Mummy – The Use of Non-Destructive Imaging to Reconstruct an Ancient Osteobiography and to Document Modern Malfeasance

An Egyptian mummy and her coffin dating to the 26th Dynasty were donated to the École de Beaux Arts in Montreal in 1927. This mummy has been in the collection of the Université du Québec à Montréal since 1967. Inscriptions on the elaborate coffin identify the individual as Hetep-Bastet. In 1969, the mummy was attacked by a protester, who caused extensive damage. The mummy was scanned once over a decade ago. However, computed tomography (CT) technology has advanced a great deal since that time, and some conclusions reached were somewhat suspect (e.g. that she suffered from a large dental abscess caused by “drinking too much beer”). Thus, when Hetep-Bastet was transported to Gatineau in the fall of 2008 to be part of the “Tombs for Eternity” exhibit at the Canadian Museum of Civilization, we took the opportunity to rescan her. The specific goals of our study were: to assess the damage done by the protester in 1969 to investigate the specific details of how she was mummified as part of an ongoing study of variability in mummification practice to gather osteological and paleopathological data in order to reconstruct her osteobiography to segment the skull from the CT data in order to create a facial reconstruction to examine her coffin as part of an ongoing study of the use of CT scans to characterize different materials associated with Egyptian mummies Damag

Vasopressin versus norepinephrine infusion in patients with septic shock

Background Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline

Purpose: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. Methods: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. Results: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). Conclusions: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians

Evaluation and management of patients with chronic thromboembolic pulmonary hypertension: consensus statement from the ISHLT

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.Thrombosis and Hemostasi