Evaluating the Quality, Accuracy, and Readability of Online Resources Pertaining to Hallux Valgus.

BACKGROUND: The Internet is one of the most widely utilized resources for health-related information. Evaluation of the medical literature suggests that the quality and accuracy of these resources are poor and written at inappropriately high reading levels. The purpose of our study was to evaluate the quality, accuracy, and readability of online resources pertaining to hallux valgus. METHODS: Two search terms ("hallux valgus" and "bunion") were entered into Google, Yahoo, and Bing. With the use of scoring criteria specific to hallux valgus, the quality and accuracy of online information related to hallux valgus was evaluated by 3 reviewers. The Flesch-Kincaid score was used to determine readability. Statistical analysis was performed with t tests and significance was determined by P values <.05. RESULTS: Sixty-two unique websites were evaluated. Quality was significantly higher with use of the search term "bunion" as compared to "hallux valgus" (P = .045). Quality and accuracy were significantly higher in resources authored by physicians as compared to nonphysicians (quality, P = .04; accuracy, P < .001) and websites without commercial bias (quality, P = .038; accuracy, P = .011). However, the reading level was significantly more advanced for websites authored by physicians (P = .035). Websites written above an eighth-grade reading level were significantly more accurate than those written at or below an eighth-grade reading level (P = .032). CONCLUSION: The overall quality of online information related to hallux valgus is poor and written at inappropriate reading levels. Furthermore, the search term used, authorship, and presence of commercial bias influence the value of these materials. It is important for orthopaedic surgeons to become familiar with patient education materials, so that appropriate recommendations can be made regarding valuable resources. LEVELS OF EVIDENCE: Level IV.

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice.

We have considered a novel gene targeting approach for treating pathologies and conditions whose genetic bases are defined using diet and nutrition. One such condition is Down syndrome, which is linked to overexpression of RCAN1 on human chromosome 21 for some phenotypes. We hypothesize that a decrease in RCAN1 expression with dietary supplements in individuals with Down syndrome represents a potential treatment. Toward this, we used in vivo studies and bioinformatic analysis to identify potential healthy dietary RCAN1 expression modulators. We observed Rcan1 isoform 1 (Rcan1-1) protein reduction in mice pup hippocampus after a 4-week curcumin and fish oil supplementation, with only fish oil reduction being statistically significant. Focusing on fish oil, we observed a 17% Rcan1-1 messenger RNA (mRNA) and 19% Rcan1-1 protein reduction in BALB/c mice after 5 weeks of fish oil supplementation. Fish oil supplementation starting at conception and in a different mouse strain (C57BL) led to a 27% reduction in hippocampal Rcan1-1 mRNA and a 34% reduction in spleen Rcan1-1 mRNA at 6 weeks of age. Hippocampal protein results revealed a modest 11% reduction in RCAN1-1, suggesting translational compensation. Bioinformatic mining of human fish oil studies also revealed reduced RCAN1 mRNA expression, consistent with the above studies. These results suggest the potential use of fish oil in treating Down syndrome and support our strategy of using select healthy dietary agents to treat genetically defined pathologies, an approach that we believe is simple, healthy, and cost-effective.

Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment.

OBJECTIVES: Recent evidence supports the involvement of RCAN1 in Down syndrome and Alzheimer's disease. To better assess this, we generated and analyzed transgenic mice overexpressing human RCAN1 isoform 4 in neurons. METHODS: Cognitive behavioral (Morris water maze, open field, zero maze, elevated plus maze assays); cognitive-associated proteins (CREB, ERK and Tau Western immunoblotting); motor coordination (Rotarod assay); structural abnormalities (immunohistological analyses), and proinflammatory cytokines (cytometric bead assay) were measured in young (2 month) and old (18 month) transgenics and compared with wild type controls. RESULTS: In old mice, male but not female transgenics exhibited a significant decrease in anxiety as compared with wild type controls, whereas female but not male transgenic mice exhibited significantly less motor coordination. No differences were observed in the Morris water maze (spatial learning). pERK levels were reduced in transgenic males but not females, while no differences were observed between genotypes for pCREB and pTau. In young mice, a modest learning and exploratory behavior was observed in transgenic mice using a limited number of mice, and at higher N values, pCREB and pERK (but not pTau) levels were reduced in transgenics. No macro- and micro-scopic structural abnormalities or proinflammatory cytokine level differences were observed. DISCUSSION: These results indicate that elevated RCAN1 isoform 4 in neurons leads to a modest cognition-related impairment that is overall stronger at 2 months, suggesting a compensatory adaptation over time. These RCAN1 isoform 4 effects may contribute to at least some of the observed phenotypes in individuals with Down syndrome and Alzheimer's.

Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration.

We previously showed a preferential degradation and down-regulation of mitochondrial DNA and RNA in hamster fibroblasts in response to hydrogen peroxide. Subsequent studies by others demonstrated that mitochondrial DNA can stimulate immune cells as a DAMP (damage associated molecular patterns) family member. However, the actual physical structure of this mitochondrial DNA DAMP and its importance in non-immune cell types are poorly understood. Here we report that transfected oxidant-initiated degraded mitochondrial polynucleotides, which we term "DeMPs", strongly induce the proinflammatory cytokines interleukin 6, monocyte chemotactic protein-1, and tumor necrosis factor α in mouse primary astrocytes. Additionally, proinflammatory IL1ß was induced, implicating DeMPs in inflammasome activation. Furthermore, human cerebrospinal fluid (CSF) and plasma were found to contain detectable DeMP signal. Finally, significant degradation of mitochondrial DNA was observed in response to either a bolus or steady state hydrogen peroxide. Combined, these studies demonstrate, all for the first time, that a pathophysiologically relevant form of mitochondrial DNA (degraded) can elicit a proinflammatory cytokine induction; that a brain cell type (astrocytes) elicits a proinflammatory cytokine induction in response to these DeMPs; that this induction includes the inflammasome; that astrocytes are capable of inflammasome activation by DeMPs; that DeMPs are detectable in CSF and plasma; and that hydrogen peroxide can stimulate an early stage cellular degradation of mitochondrial DNA. These results provide new insights and are supportive of our hypothesis that DeMPs are a newly identified trigger of neurodegenerative diseases such as Alzheimer's disease, which are known to be associated with early stage inflammation and oxidation.