Subject(s)
Adalimumab/immunology , Antibodies, Anti-Idiotypic/blood , Crohn Disease/drug therapy , HLA-DQ alpha-Chains/genetics , Haplotypes , Infliximab/immunology , Polymorphism, Genetic , Tumor Necrosis Factor Inhibitors/immunology , Adalimumab/adverse effects , Crohn Disease/blood , Crohn Disease/diagnosis , Crohn Disease/immunology , Epitopes , HLA-DQ alpha-Chains/immunology , Humans , Infliximab/adverse effects , Treatment Outcome , Tumor Necrosis Factor Inhibitors/adverse effectsABSTRACT
Alzheimer's Disease (AD) is the sixth leading cause of death in the United States. Recent studies have established a potential link between herpes simplex virus 1 (HSV-1) infection and the development of AD. HSV-1 DNA has been detected in AD amyloid plaques in human brains, and treatment with the antiviral acyclovir (ACV) was reported to block the accumulation of the AD-associated proteins beta-amyloid (Aß) and hyper-phosphorylated tau (p-tau) in Vero and glioblastoma cells. Our goal was to determine whether the accumulation of AD-related proteins is attributable to acute and/or latent HSV-1 infection in mature hippocampal neurons, a region of the brain severely impacted by AD. Primary adult murine hippocampal neuronal cultures infected with HSV-1, with or without antivirals, were assessed for Aß and p-tau expression over 7 days postinfection. P-tau expression was transiently elevated in HSV-1-infected neurons, as well as in the presence of antivirals alone. Infected neurons, as well as uninfected neurons treated with antivirals, had a greater accumulation of Aß42 than uninfected untreated neurons. Furthermore, Aß42 colocalized with HSV-1 latency-associated transcript (LAT) expression. These studies suggest that p-tau potentially acts as an acute response to any perceived danger-associated molecular pattern (DAMP) in primary adult hippocampal neurons, while Aß aggregation is a long-term response to persistent threats, including HSV-1 infection.IMPORTANCE Growing evidence supports a link between HSV-1 infection and Alzheimer's disease (AD). Although AD is clearly a complex multifactorial disorder, an infectious disease etiology provides alternative therapy opportunities for this devastating disease. Understanding the impact that HSV-1 has on mature neurons and the proteins most strongly associated with AD pathology may identify specific mechanisms that could be manipulated to prevent progression of neurodegeneration and dementia.
Subject(s)
Amyloid beta-Peptides/metabolism , Herpesvirus 1, Human/physiology , Neurons/metabolism , Acyclovir/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/virology , Amyloid beta-Protein Precursor/metabolism , Animals , Antiviral Agents/pharmacology , Brain/metabolism , Chlorocebus aethiops , Female , Herpes Simplex/metabolism , Herpesvirus 1, Human/metabolism , Herpesvirus 1, Human/pathogenicity , Hippocampus/metabolism , Mice , Neurons/virology , Peptide Fragments/metabolism , Phosphorylation , Plaque, Amyloid/metabolism , Primary Cell Culture , Vero Cells , Virus Replication/drug effects , tau Proteins/metabolism , tau Proteins/pharmacologyABSTRACT
BACKGROUND: Diagnosing NAT (non-accidental trauma) includes a skeletal survey to identify injuries. A follow-up survey is performed for missed injuries. This study examines the necessity of follow-up surveys. METHODS: The trauma database identified cases of suspected NAT in <4 years olds (2013-2014). Data were stratified by survey, age, injury, then analyzed for the prevalence of findings. All analyses (relative risk, prevalence and odds ratios) utilized RealStats Resource Pack (Trento, Italy). RESULTS: 79% positive initial findings and no new follow up findings. Those with negative initial imaging, had no missed injuries. Initial scans were 27.6X more likely to be positive. Fractured skull (31.3), femur (17.2) and ribs (15.7) were the most prevalent. No pelvic fractures and <1% spinal injuries despite both having the greatest radiation exposure. Repeat scans rarely identify findings for age >12 months. CONCLUSIONS: Follow-up skeletal surveys maybe unnecessary without clinical evidence. Uncommon pelvic and spinal fractures may warrant exclusion from surveys unless clinically indicated.
