Acute Toxin-Mediated Rhabdomyolysis During Treatment ith Trimethoprim-Sulfamethoxazole

Rhabdomyolysis is a condition in which skeletal muscle breakdown causes the release of intracellular components into the bloodstream – defined as elevations in serum creatine kinase levels. The etiology of rhabdomyolysis is varied and may be the result of toxin-mediated mechanisms or metabolic derangements, or they may develop secondary to other conditions such as seizures, trauma and prolonged immobilization. In this case, we present a patient with suspected acute toxin-mediated rhabdomyolysis in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) therapy for urinary tract infection. To our knowledge, this marks the fifth case report of an otherwise healthy patient diagnosed with rhabdomyolysis thought to be secondary to TMP-SMX

An Omnidirectional Aerial Manipulation Platform for Contact-Based Inspection

This paper presents an omnidirectional aerial manipulation platform for robust and responsive interaction with unstructured environments, toward the goal of contact-based inspection. The fully actuated tilt-rotor aerial system is equipped with a rigidly mounted end-effector, and is able to exert a 6 degree of freedom force and torque, decoupling the system's translational and rotational dynamics, and enabling precise interaction with the environment while maintaining stability. An impedance controller with selective apparent inertia is formulated to permit compliance in certain degrees of freedom while achieving precise trajectory tracking and disturbance rejection in others. Experiments demonstrate disturbance rejection, push-and-slide interaction, and on-board state estimation with depth servoing to interact with local surfaces. The system is also validated as a tool for contact-based non-destructive testing of concrete infrastructure.Comment: Accepted submission to Robotics: Science and Systems conference 2019. 9 pages, 12 figure

2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA

Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions where it would be advantageous. Glucose and glutamine consumption are increased in mtDNA dysfunction, and so we targeted the use of both in cells carrying the pathogenic m.3243A>G variant with 2-Deoxy-D-glucose (2DG), or the related 5-thioglucose. Here, we show that both compounds selected wild-type over mutant mtDNA, restoring mtDNA expression and respiration. Mechanistically, 2DG selectively inhibits the replication of mutant mtDNA; and glutamine is the key target metabolite, as its withdrawal, too, suppresses mtDNA synthesis in mutant cells. Additionally, by restricting glucose utilization, 2DG supports functional mtDNAs, as glucose-fuelled respiration is critical for mtDNA replication in control cells, when glucose and glutamine are scarce. Hence, we demonstrate that mitochondrial fitness dictates metabolite preference for mtDNA replication; consequently, interventions that restrict metabolite availability can suppress pathological mtDNAs, by coupling mitochondrial fitness and replication.publishedVersio

Acute Toxin-Mediated Rhabdomyolysis During Treatment ith Trimethoprim-Sulfamethoxazole

Rhabdomyolysis is a condition in which skeletal muscle breakdown causes the release of intracellular components into the bloodstream – defined as elevations in serum creatine kinase levels. The etiology of rhabdomyolysis is varied and may be the result of toxin-mediated mechanisms or metabolic derangements, or they may develop secondary to other conditions such as seizures, trauma and prolonged immobilization. In this case, we present a patient with suspected acute toxin-mediated rhabdomyolysis in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) therapy for urinary tract infection. To our knowledge, this marks the fifth case report of an otherwise healthy patient diagnosed with rhabdomyolysis thought to be secondary to TMP-SMX