Background Adults with low literacy may encounter informational obstacles on the Internet when searching for health information, in part because most health Web sites require at least a high-school reading proficiency for optimal access.Objective The purpose of this study was to 1) determine how low-literacy adults independently access and evaluate health information on the Internet, 2) identify challenges and areas of proficiency in the Internet-searching skills of low-literacy adults.Methods Subjects (n=8) were enrolled in a reading assistance program at Bidwell Training Center in Pittsburgh, PA, and read at a 3rd to 8th grade level. Subjects conducted self-directed Internet searches for designated health topics while utilizing a think-aloud protocol. Subjects' keystrokes and comments were recorded using Camtasia Studio screen-capture software. The search terms used to find health information, the amount of time spent on each Web site, the number of Web sites accessed, the reading level of Web sites accessed, and the responses of subjects to questionnaires were assessed.Results Subjects collectively answered 8 out of 24 questions correctly. Seven out of 8 subjects selected "sponsored sites"-paid Web advertisements-over search engine-generated links when answering health questions. On average, subjects accessed health Web sites written at or above a 10th grade reading level. Standard methodologies used for measuring health literacy and for promoting subjects to verbalize responses to Web-site form and content had limited utility in this population.Conclusion This study demonstrates that Web health information requires a reading level that prohibits optimal access by some low-literacy adults. These results highlight the low-literacy adult population as a potential audience for Web health information, and indicate some areas of difficulty that these individuals face when using the Internet and health Web sites to find information on specific health topics.

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We have previously shown that insulin-like growth factor (IGF) binding protein-5 (IGFBP-5) is overexpressed in lung fibrosis and induces the production of extracellular matrix components, such as collagen and fibronectin, both in vitro and in vivo. The exact mechanism by which IGFBP-5 exerts these novel fibrotic effects is unknown. We thus examined the signaling cascades that mediate IGFBP-5-induced fibrosis. We demonstrate for the first time that

The signal transducing protein Stat3 activates gene transcription in cells in response to multiple cytokines. Constitutive activation of Stat3 has been observed in solid tumors including head and neck squamous cell carcinoma. Stat3 activation in cancer has been associated with autocrine stimulatory loops and is believed to convey a growth advantage to cells. We now demonstrate ligandindependent activation of Stat3 by high cell density in multiple cancer cell lines. Activation of Stat3 is associated with antiproliferative rather than proliferative conditions. Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity. Our data supports a model in which Stat3 activity is partially suppressed by cdk2 in growing cells and derepressed upon cell confluence.

Background Aicardi-Goutières syndrome (AGS) is a severe infant or juvenile-onset autoimmune disease characterized by inflammatory encephalopathy with an elevated type 1 interferon-stimulated gene (ISG) expression signature in the brain. Mutations in seven different protein-coding genes, all linked to DNA/RNA metabolism or sensing, have been identified in AGS patients, but none of them has been demonstrated to activate the IFN pathway in the brain of an animal. The molecular mechanism of inflammatory encephalopathy in AGS has not been well defined. Adenosine Deaminase Acting on RNA 1 (ADAR1) is one of the AGS-associated genes. It carries out A-to-I RNA editing that converts adenosine to inosine at double-stranded RNA regions. Whether an AGS-associated mutation in ADAR1 activates the IFN pathway and causes autoimmune pathogenesis in the brain is yet to be determined. Methods Mutations in the ADAR1 gene found in AGS patients were introduced into the mouse genome via CRISPR/Cas9 technology. Molecular activities of the specific p.K999N mutation were investigated by measuring the RNA editing levels in brain mRNA substrates of ADAR1 through RNA sequencing analysis. IFN pathway activation in the brain was assessed by measuring ISG expression at the mRNA and protein level through real-time RT-PCR and Luminex assays, respectively. The locations in the brain and neural cell types that express ISGs were determined by RNA in situ hybridization (ISH). Potential AGS-related brain morphologic changes were assessed with immunohistological analysis. Von Kossa and Luxol Fast Blue staining was performed on brain tissue to assess calcification and myelin, respectively. Results Mice bearing the ADAR1 p.K999N were viable though smaller than wild type sibs. RNA sequencing analysis of neuron-specific RNA substrates revealed altered RNA editing activities of the mutant ADAR1 protein. Mutant mice exhibited dramatically elevated levels of multiple ISGs within the brain. RNA ISH of brain sections showed selective activation of ISG expression in neurons and microglia in a patchy pattern. ISG-15 mRNA was upregulated in ADAR1 mutant brain neurons whereas CXCL10 mRNA was elevated in adjacent astroglia. No calcification or gliosis was detected in the mutant brain. Conclusions We demonstrated that an AGS-associated mutation in ADAR1, specifically the p.K999N mutation, activates the IFN pathway in the mouse brain. The ADAR1 p.K999N mutant mouse replicates aspects of the brain interferonopathy of AGS. Neurons and microglia express different ISGs. Basal ganglia calcification and leukodystrophy seen in AGS patients were not observed in K999N mutant mice, indicating that development of the full clinical phenotype may need an additional stimulus besides AGS mutations. This mutant mouse presents a robust tool for the investigation of AGS and neuroinflammatory diseases including the modeling of potential “second hits” that enable severe phenotypes of clinically variable diseases.

Background: Prior studies indicate that leukemias expressing high levels of the p21WAF1 cell cycle inhibitor have a poorer prognosis than p21WAF1negative leukemias. Although p21WAF1 is upregulated by p53 in the setting of DNA damage, the prognostic significance of p21WAF1 is independent of p53 status. The molecular basis of the negative prognostic effect of p21WAF1 remains obscure, but it is believed to result from decreased apoptosis of p21WAF1-expressing leukemias. Materials and Methods: We studied the effects of p21WAF1 on apoptosis of K562 leukemic cells, which lack wild-type p53 and do not express endogenous p21WAF1. An inducible p21WAF1 system was used and the effect of p21WAF1 induction on susceptibility to etoposide-mediated apoptosis was measured. Results: p21WAF1 decreased apoptotic death of K562 leukemic cells in response to etoposide. Analysis of intermediaries in the apoptotic pathway indicated that p21WAF1 had no effect on cytochrome c release or cleavage of procaspase-3. In contrast, p21WAF1 was protective against cleavage of caspase targets poly(ADP-ribose)polymerase (PARP), retinoblastoma protein (Rb), and lamin. The expression of the inhibitor of apoptosis protein c-IAP1, which inhibited the function of executioner caspases 3 and 7, was studied. c-IAP1 protein expression was found to be present in a majority of leukemic blasts from untreated patients, but absent in normal differentiating myeloid progenitor cells. In K562 cells, treatment with etoposide in the absence of p21WAF1 induction resulted in post-transcriptional down-modulation of c-IAP1 levels. c-IAP1 loss involved proteasomal, rather than caspase, degradation pathways. Expression of p21WAF1 sustained c-IAP1 protein levels in the presence of etoposide. Conclusions: Etoposide-mediated apoptosis involves down-modulation of the anti-apoptotic protein c-IAP1. Our findings support the hypothesis that p21WAF1 contributes to leukemic chemoresistance by stabilizing c-IAP1 levels in the presence of chemotherapy.

African Americans with low incomes and low literacy levels disproportionately suffer poor health outcomes from many preventable diseases. Low functional literacy and low health literacy impede millions of Americans from successfully accessing health information. These problems are compounded for African Americans by cultural insensitivity in health materials. The Internet could become a useful tool for providing accessible health information to low-literacy and low-income African Americans. Optimal health Web sites should include text written at low reading levels and appropriate cultural references. More research is needed to determine how African Americans with low literacy skills access, evaluate, prioritize, and value health information on the Internet.

An interactive trading card format is a useful method for conveying information about host defence.