TRPV4 stimulates colonic afferents through mucosal release of ATP and glutamate.

Background And Purpose: Abdominal pain is a leading cause of morbidity for people living with gastrointestinal disease. Whereas the transient receptor potential vanilloid 4 (TRPV4) ion channel has been implicated in the pathogenesis of abdominal pain, the relative paucity of TRPV4 expression in colon-projecting sensory neurons suggests that non-neuronal cells may contribute to TRPV4-mediated nociceptor stimulation.

Experimental Approach: Changes in murine colonic afferent activity were examined using ex vivo electrophysiology in tissues with the gut mucosa present or removed.

Novel therapies for cancer-induced bone pain.

Cancer pain is a growing problem, especially with the substantial increase in cancer survival. Reports indicate that bone metastasis, whose primary symptom is bone pain, occurs in 65-75% of patients with advanced breast or prostate cancer. We optimized a preclinical model of cancer-induced bone pain (CIBP) involving the injection of Lewis Lung Carcinoma cells into the intramedullary space of the femur of C57BL/6 mice or transgenic mice on a C57BL/6 background.

MEDI1814 selectively reduces free Aβ42 in cerebrospinal fluid of non-clinical species and Alzheimer's disease patients.

Introduction: Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.

Methods: We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ, the pathogenic self-aggregating species of Aβ.

Results: MEDI1814 reduces free Aβ without impacting Aβ in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration.

Frailty and Long-Term Mortality Following Emergency Laparotomy: A Comparison Between the 11-Item and 5-Item Modified Frailty Indices.

Introduction: Emergency laparotomy (EL) is a high-risk operation which is increasingly performed on an aging patient population. Objective frailty assessment using a validated index has the potential to improve preoperative risk stratification. This study aimed to assess the correlation between frailty and long-term mortality and morbidity outcomes for older EL patients.