Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV

The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3. Differentiating hNP1 cells were exposed for 16 days to HIV- or mock-infected supernatants and to added recombinant ApoE isoforms rApoE3 or rApoE4 to modulate the ApoE phenotype of the cells. Gene expression was investigated using microarray and functional genomics analyses. Added rApoE3 differentially affected 36 genes. Added rApoE4 differentially affected 85 genes; 41 of which were differentially expressed only in HIV or mock-supernatant treated cells, and 80% of which were downregulated. Genes differentially downregulated only by rApoE4 represented multiple neuronal functions related to neurogenesis. Approximately five times more genes were differentially enriched by rApoE4 versus rApoE3 in the Gene Ontology (GO) cellular process analysis, with 4 orders of magnitude greater significance. Half of the top 10 GO processes affected by rApoE4 treatment were neurogenesis-related. The largest differences in gene expression between the two isoforms were observed within the HIV-exposed cultures, suggesting that HIV exposure magnifies ApoE4's suppressive effect on neuronal gene expression. This study provides evidence for neuronal-specific responses to ApoE4 that could affect neurogenesis and neuronal survival

Management of Rotator Cuff Injuries in the Elite Athlete

PURPOSE OF REVIEW:Rotator cuff injuries are a common cause of pain and dysfunction for the elite athlete and can result in time loss from participation. This review highlights the current management of these injuries. RECENT FINDINGS:Conservative management of rotator cuff injuries continues to be the "gold standard" in the elite athlete. This includes a comprehensive rehabilitation program, anti-inflammatories, and corticosteroid injections. Newer treatment techniques such as intramuscular dry needling and the use of biologics such as platelet-rich plasma and stem cells demonstrate early promising results; however, these modalities require further investigation to determine their effectiveness. Rotator cuff injuries can range from contusions and tendinopathy to full-thickness tears. A comprehensive evaluation is needed to determine the extent of injury and appropriate plan of care. Management strategies can range from rehabilitation to operative intervention and are guided by the size of the tear, time of season, sport, performance limitations, and presence of concomitant pathology