Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE).

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS), is a multisystem illness characterized by extreme muscle fatigue associated with pain, neurocognitive impairment, and chronic inflammation. Despite intense investigation, the molecular mechanism of this disease is still unknown. Here we demonstrate that autophagy-related protein ATG13 is strongly upregulated in the serum of ME/CFS patients, indicative of impairment in the metabolic events of autophagy. A Thioflavin T-based protein aggregation assay, array screening for autophagy-related factors, densitometric analyses, and confirmation with ELISA revealed that the level of ATG13 was strongly elevated in serum samples of ME/CFS patients compared to age-matched controls. Moreover, our microglia-based oxidative stress response experiments indicated that serum samples of ME/CFS patients evoke the production of reactive oxygen species (ROS) and nitric oxide in human HMC3 microglial cells, whereas neutralization of ATG13 strongly diminishes the production of ROS and NO, suggesting that ATG13 plays a role in the observed stress response in microglial cells. Finally, an in vitro ligand binding assay provided evidence that ATG13 employs the Receptor for Advanced Glycation End-products (RAGE) to stimulate ROS in microglial cells. Collectively, our results suggest that an impairment of autophagy following the release of ATG13 into serum could be a pathological signal in ME/CFS.

Primary anterior cruciate ligament repair: Current concepts.

The renewed interest in ACL repair over the last two decades stems from advances in modern arthroscopic techniques and clinical studies that have provided evidence that the ACL can reliably heal, and patients can return to sport at a comparable rate to ACL reconstruction patients. The ability to maintain and utilize native ACL tissue, with proprioceptive capabilities, and the smaller drill tunnels needed to repair an ACL leads to an overall less invasive procedure and improved early rehabilitation. Additionally, repair avoids a variety of comorbidities associated with autograft harvest. This current concept review details modern techniques of ACL repair and their current studies, a review on the use of biologic enhancement in ACL repair, and other considerations to appropriately integrate ACL repair into the sports medicine orthopaedic surgeon's practice.