SENSORY NEURON INSULIN SIGNALING AND ITS ROLE IN DIABETIC NEUROPATHY

Diabetes is a global concern; approximately 366 million people are currently diagnosed worldwide. Complications of diabetes are numerous and can cause damage to almost every organ system in the body. Neuropathy is the most common complication associated with diabetes and severely impacts patients' quality of life. Diabetic neuropathy (DN) most commonly present as a distal symmetric polyneuropathy with a dichotomous presentation of either peripheral insensitivity or chronic pain. Eventually, patients can develop injury unawareness and foot ulcers, often resulting in amputation. Clearly establishing the mechanisms of diabetes-induced nerve damage will drive the development of more targeted and appropriate treatments. The pathogenesis of DN is multifactorial and the majority of research currently focuses on the toxic pathways induced by hyperglycemia. Interestingly though, insulin has been recently characterized to have direct effects on sensory neurons and is now believed to be a neurotrophic factor that is required for proper development, growth, and maintenance of the nervous system. Here, we tested the hypothesis that reduced sensory neuron insulin signaling contributes to DN pathogenesis via disrupted neurotrophic support. Results demonstrate that PI3K-Akt pathway activation in sensory neurons is insulin dose dependent and that insulin supplementation increases neurite outgrowth, establishing that sensory neurons are insulin responsive. These responses are blunted in type 2 diabetic mice, indicating that sensory neurons demonstrate signs of insulin resistance similar to muscle, liver, and adipose. However, sensory neuron insulin receptor knockout (SNIRKO) mice that maintain euglycemia do not display signs of DN. Suggesting that a disruptions solely in sensory neuron insulin signaling does not cause DN. Surprisingly though, SNIRKO mice are hyperinsulinemic and pancreatic islets from SNIRKO mice display increased insulin content, suggesting a possible feedback mechanism between sensory neuron insulin signaling and insulin production. These results are consistent with a recently described novel pathway of pancreatic beta cell regulation via sensory neuron neuropeptides. In conclusion, while sensory neurons are insulin responsive, reductions in sensory neuron insulin signaling without hyperglycemia does not cause signs of DN and it is most likely the combination of reduced insulin support and glucose neurotoxicity. Furthermore, the generation of SNIRKO mice has outlined a possible feedback mechanism through which sensory neurons modulate insulin production that could possible aid in establishing new therapeutic avenues for the treatment of diabetes

Primary Arthrodesis for Diabetic Ankle Fractures

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Treatment of ankle fractures in patients with diabetes is associated with increased complication rates. Ankle arthrodesis is considered a salvage procedure after failed ankle fracture fixation, yet primary ankle arthrodesis has been proposed as a treatment option for patients with significant diabetes-related complications. To date, the characteristics of patients who undergo primary ankle arthrodesis and the associated outcomes have not been described. Methods: A retrospective review was performed of 13 patients with diabetes who underwent primary arthrodesis for traumatic ankle fracture. Patient demographics were characterized in addition to their diabetes complications, Adelaide Fracture in the Diabetic Ankle (AFDA) score, and fracture type. Outcomes assessed included reoperation rates, infection rates, wound complications, nonunion/malunion, amputation, and development of Charcot arthropathy postoperatively. Results: Patients who underwent primary arthrodesis had high rates of diabetes complications, average AFDA scores of 6.4, and high rates of severe injuries, including 38.5% open fractures and 69.2% fracture dislocations. The overall complication rate for primary arthrodesis of ankle fractures in diabetes patients was more than 75% in this cohort. Complications included a 38.5% reoperation rate, 38.5% infection rate, 53.8% wound complication rate, and 23.1% amputation rate. Despite a high nonunion rate at the attempted fusion sites, 89.9% of fractures healed and patients had a stable extremity. Conclusion: This review is the first to characterize the epidemiology and complications of diabetes patients undergoing primary ankle arthrodesis for ankle fractures. In this cohort, patients with multiple diabetic complications and severe injuries underwent primary arthrodesis, which led to an overall high complication rate. Further research is needed to determine the appropriate treatment option for these high-risk patients, and tibiotalocalcaneal stabilization without arthrodesis may be beneficial

Pseudotumor from Metal-on-Metal Total Hip Arthroplasty Causing Unilateral Leg Edema: Case Presentation and Literature Review

Metal-on-metal (MoM) total hip arthroplasty (THA) can be associated with adverse metal reactions, including pseudotumors. This case report describes a 58-year-old female with an MoM THA-related pseudotumor that caused unilateral leg edema from compression of her external iliac vein. After thorough preoperative workup to rule out infection and deep vein thrombosis and consultation with a vascular surgeon, the patient underwent revision THA and excision of her pseudotumor. She had complete resolution of her swelling at 4 years after surgery. Review of all available case reports for this rare complication revealed that almost all patients were female. All patients underwent revision THA, with resolution of their symptoms. Literature review demonstrates that women are disproportionally affected by complications associated with MoM THA. We recommend close monitoring of patients with MoM THA, particularly women, for development of adverse metal reactions

Innovations to Overcome the Increasingly Complex Problems of Hunger

Hunger has become ever more complex, and therefore efforts to sustainably eradicate hunger and malnutrition depend on policies and programs that match these complexities. Innovations are critical for progress. However, they require increased public and private investments as well. Key elements of inclusive policies and partnerships are agricultural development in the hunger-affected rural areas and communities to improve productivity will remain a Major part of solutions. Farmers’ own innovation capacities need strengthening. Investment in Food and agricultural research and development (R&D) is an important tool for broad-based innovation, for instance, related to improved seeds. Digital technology is a game changer for food and nutrition security. Innovations for improved market functioning and avoidance of price shocks require information and early warning systems, as well as better preparedness with improved trade and food reserves policies. The environmental and climate change aspects of agricultural and land and water use change need more attention for sustainable hunger reduction. More attention to innovative social protection and direct nutrition intervention programs is needed, including addressing the micronutrient deficiencies in rural and urban areas. Hunger in complex emergencies needs to bring together development policy with diplomacy and security policy. Innovation initiatives like any development Investments must follow principles of good governance, achieving investment at low transaction costs, sound financial practices, and avoidance of diversions of funds