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The persistence of HIV in the central nervous system leads to cognitive deficits in up to 50% of people living with HIV even with systemic suppression by antiretroviral treatment. The interaction of chronic inflammation with age-associated degeneration places these individuals at increased risk of accelerated aging and other neurodegenerative diseases and no treatments are available that effectively halt these processes. The adverse effects of aging and inflammation may be mediated, in part, by an increase in the expression of the p75 neurotrophin receptor (p75 NTR ) which shifts the balance of neurotrophin signaling toward less protective pathways. To determine if modulation of p75 NTR could modify the disease process, we treated HIV gp120 transgenic mice with a small molecule ligand designed to engage p75 NTR and downregulate degenerative signaling. Daily treatment with 50 mg/kg LM11A-31 for 4 months suppressed age- and genotype-dependent activation of microglia, increased microtubule associated protein-2 (MAP-2), reduced dendritic varicosities and slowed the loss of parvalbumin immunoreactive neurons in the hippocampus. An age related accumulation of microtubule associated protein Tau was identified in the hippocampus in extracellular clusters that co-expressed p75 NTR suggesting a link between Tau and p75 NTR . Although the significance of the relationship between p75 NTR and Tau is unclear, a decrease in Tau-1 immunoreactivity as gp120 mice entered old age (>16 months) suggests that the Tau may transition to more pathological modifications; a process blocked by LM11A-31. Overall, the effects of LM11A-31 are consistent with strong neuroprotective and anti-inflammatory actions that have significant therapeutic potential., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cancer of the appendix is rare and is most commonly found incidentally on pathology after an appendectomy for uncomplicated appendicitis (UA). The medical management alternative with antibiotics and observation remains an ongoing debate. The purpose of our study was to develop modern epidemiological data for adult patients completing an appendectomy for UA secondary to an appendiceal neoplasm (AN). ACS-NSQIP database was queried (2005-2016) to identify patients completing an appendectomy. Cohorts of patients who were diagnosed with UA and an AN were included in the study. Relevant perioperative clinical and outcomes data were collected. Type of AN, surgical procedure, and mortality were analyzed. A total of 239,615 UA patients were identified, of whom 2,773 (1.2%) met the inclusion criteria of AN. Patients with AN were predominantly white (79.5%), with a mean age of 54.5 ± 15.9 years, and 54.6 per cent were females. AN pathology findings included malignant neoplasm (64.5%), malignant carcinoid (17.3%), benign carcinoid (9.3%), and benign neoplasm (8.8%). The overall reported incidence was 1.2 per cent and the mortality rate was 0.7 per cent. Our study emphasizes surgical intervention in adult UA maintains a 1 per cent incidence of AN, and treatment with antibiotics alone will presumably lead to a delay in surgical treatment and progression of disease.