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Environmental enrichment (EE) has been shown to improve cognitive performance and brain indices of cognition in normal mice and rats. Because the therapeutic potential of intensive, long-term EE to benefit patients with Alzheimer's disease (AD) has yet to be explored, the present study evaluated the effect of long-term EE on cognition in an animal model of AD, the APPsw transgenic mouse. Beginning at 16 months of age, APPsw mice were put into EE or standard housing for 4 months and then tested in four cognitive-based tasks (Morris maze, circular platform, platform recognition, and radial arm water maze) between 20 and 22 months of age. Our results indicate that long-term EE of aged APPsw mice results in global, overall improvement in cognitive function across these tasks without decreasing brain beta-amyloid (A beta) deposition. The results suggest that long-term EE/cognitive stimulation could provide cognitive stabilization or improvement to AD patients through mechanisms independent of A beta deposition and clearance.

Background There has been increasing interest in primary surgical treatment of patients with early T classification (T1–T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. We sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse post-operative pathologic features. Methods Patients with T1–T2 OPSCC in the National Cancer Database (NCDB) treated from 2004–2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to selection of primary surgery were examined. The rates of adverse pathologic features including positive margins, extracapsular spread (ECS), and advanced T and N stage following surgery were analyzed. Results Of 8,768 patients with T1–T2 OPSCC, 68% received primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (p<0.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (O.R. 2.23 C.I. 1.55–3.22, p<0.0001). Higher nodal stage predicted lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among surgical patients, positive margins were present in 24% and ECS in 25%. Positive margins decreased over time (p<0.0001) and were seen less often at high volume centers (p<0.0001). Among candidates for single modality therapy (clinical T1–T2/N0–N1), 33% had positive margins and/or ECS, and 47% had at least one adverse feature (T3–T4, N2–N3, positive margins, and/or ECS). Conclusion Primary surgical treatment for early T-stage OPSCC has become more widespread.

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Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer's disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four housing conditions (impoverished, social, social+physical, or complete enrichment) from 1(1/2) through 9 months of age. Thus, a stepwise layering of social, physical, and enhanced cognitive activity was created. Behavioral evaluation in a full battery of sensorimotor, anxiety, and cognitive tasks was carried out during the final 5 weeks of housing. Only AD mice raised in complete enrichment (i.e., enhanced cognitive activity) showed: (1) protection against cognitive impairment, (2) decreased brain beta-amyloid deposition, and (3) increased hippocampal synaptic immunoreactivity. The protection provided by enhanced cognitive activity spanned multiple cognitive domains (working memory, reference learning, and recognition/identification). Cognitive and neurohistologic benefits of complete enrichment occurred without any changes in blood cytokine or corticosterone levels, suggesting that enrichment-dependent mechanisms do not involve changes in the inflammatory response or stress levels, respectively. These results indicate that the enhanced cognitive activity of complete enrichment is required for cognitive and neurologic benefit to AD mice-physical and/or social activity are insufficient. Thus, our data suggest that humans who emphasize a high lifelong level of cognitive activity (over and above social and physical activities) will attain the maximal environmental protection against AD.

Background and Objectives Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. Methods Cases of T1–T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. Results Of 3,071 patients who underwent primary surgical management for T1–T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs T1: OR 0.75, CI 0.37–0.51, p<0.0001; T3 vs T1: O.R. 0.33, CI 0.28–0.38, p<0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29–3.88, p=0.004) and treatment at a high volume hospital (34–155 cases vs 1–4 cases: O.R. 9.07, C.I. 3.19–25.79, p<0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume vs. low volume hospital (8.2% vs 16.7% respectively, p=0.001). Conclusions Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC.

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Here, using two human BRAF-mutated thyroid cell lines and a rat thyroid cell line expressing BRAF in a conditional manner, we show that NOX4 upregulation is controlled at the transcriptional level by the oncogene via the TGF-β/Smad3 signaling pathway. Importantly, treatment of cells with NOX4-targeted siRNA downregulates BRAF-induced NIS repression. Innovation and Conclusion: Our results establish a link between BRAF and NOX4, which is confirmed by a comparative analysis of NOX4 expression in human (TCGA) and mouse thyroid cancers. Remarkably, analysis of human and murine BRAF-mutated thyroid tumors highlights that the level of NOX4 expression is inversely correlated to thyroid differentiation suggesting that other genes involved in thyroid differentiation in addition to NIS might be silenced by a mechanism controlled by NOX4-derived ROS. This study opens a new opportunity to optimize thyroid cancer therapy. Antioxid. Redox Signal. 26, 864-877.