Joint Instability as the Cause of Chronic Musculoskeletal Pain and Its Successful Treatment with Prolotherapy

This chapter is based on the premise that treatment with prolotherapy can greatly reduce chronic musculoskeletal pain, which affects more than 1 billion people worldwide. Although relatively unknown to mainstream medicine, prolotherapy has been used for decades to treat chronic musculoskeletal pain, doing so by correcting the underlying cause of that pain: joint instability due to ligament laxity. Discussions of joint instability, ligament physiology and biomechanics, compressive and shear forces, sites of instability, pain referral patterns, and ligament injury and healing demonstrate how they all interrelate to cause chronic pain. Treating chronic pain using nonsteroidal anti-inflammatory drugs, corticosteroids, and the rest, ice, compression, and elevation protocol actually inhibit the natural healing process of injured ligaments because they interrupt the inflammatory response, prevent joint swelling, and hinder cell proliferation, resulting in further ligament laxity and tissue regrowth that is inferior to native ligament tissue. Unlike conventional treatments, prolotherapy injects small volumes of an irritant solution into painful ligaments, tendons, joints, and surrounding joint spaces, initiating an inflammatory response which then attracts substances that promote normal cell and tissue growth. Their propagation stimulates the injured ligament to proliferate and grow at the injection sites, resulting in the regeneration of new tissue

Recent Clean Air Act Developments—2006

Air is the ultimate public good. No one owns it but everyone uses it. Protecting it is clearly a great challenge. Since its inception in the mid-1960s, the federal Clean Air Act (CAA) has been a crucial component in managing this resource, but it has also been a source of strife and discontent. The law was forward-looking for its time, pressing polluters to radically change their ways, while still accounting for the fact that we would never be a zero-pollution society. It has also changed with the times, as problems that could not have been imagined in 1970, such as atmospheric ozone depletion and acid rain, have since been addressed, while other issues have been revisited as scientific understanding of atmospheric processes, such as those governing the formation of smog and the distribution of airborne toxics, has improved

Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain

Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design.Peer reviewe