RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis

Patients with inflammatory bowel diseases are at increased risk for colorectal cancer, but the molecular mechanisms linking inflammation and cancer are not well defined. We earlier showed that carboxylated N-glycans expressed on receptor for advanced glycation end products (RAGE) and other glycoproteins mediate colitis through activation of nuclear factor kappa B (NF-κB). Because NF-κB signaling plays a critical role in the molecular pathogenesis of colitis-associated cancer (CAC), we reasoned that carboxylated glycans, RAGE and its ligands might promote CAC. Carboxylated glycans are expressed on a subpopulation of RAGE on colon cancer cells and mediate S100A8/A9 binding to RAGE. Colon tumor cells express binding sites for S100A8/A9 and binding leads to activation of NF-κB and tumor cell proliferation. Binding, downstream signaling and tumor cell proliferation are blocked by mAbGB3.1, an anti-carboxylate glycan antibody, and by anti-RAGE. In human colon tumor tissues and in a mouse model of CAC, we found that myeloid progenitors expressing S100A8 and S100A9 infiltrate regions of dysplasia and adenoma. mAbGB3.1 administration markedly reduces chronic inflammation and tumorigenesis in the mouse model of CAC and RAGE-deficient mice are resistant to the onset of CAC. These findings show that RAGE, carboxylated glycans and S100A8/A9 play essential roles in tumor–stromal interactions, leading to inflammation-associated colon carcinogenesis

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Identifying evidence of effectiveness in the co-creation of research: a systematic review and meta-analysis of the international healthcare literature.

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Public Health, following peer review. The version of record: Kristoffer Halvorsrud, Justyna Kucharska, Katherine Adlington, Katja Rüdell, Eva Brown Hajdukova, James Nazroo, Maria Haarmans, James Rhodes, Kamaldeep Bhui, Identifying evidence of effectiveness in the co-creation of research: a systematic review and meta-analysis of the international healthcare literature, Journal of Public Health, fdz126, https://doi.org/10.1093/pubmed/fdz126 is available online at: https://doi.org/10.1093/pubmed/fdz126.BACKGROUND: To investigate and address the evidence gap on the effectiveness of co-creation/production in international health research. METHODS: An initial systematic search of previous reviews published by 22 July 2017 in Medline, Embase, PsycINFO, Scopus and Web of Science. We extracted reported aims, elements and outcomes of co-creation/production from 50 reviews; however, reviews rarely tested effectiveness against intended outcomes. We therefore checked the reference lists in 13 included systematic reviews that cited quantitative studies involving the public/patients in the design and/or implementation of research projects to conduct meta-analyses on their effectiveness using standardized mean difference (SMD). RESULTS: Twenty-six primary studies were included, showing moderate positive effects for community functions (SMD = 0.56, 95%CI = 0.29-0.84, n = 11) and small positive effects for physical health (SMD = 0.25, 95%CI = 0.07-0.42, n = 9), health-promoting behaviour (SMD = 0.14, 95%CI = 0.03-0.26, n = 11), self-efficacy (SMD = 0.34, 95%CI = 0.01-0.67, n = 3) and health service access/receipt (SMD = 0.36, 95%CI = 0.21-0.52, n = 12). Non-academic stakeholders that co-created more than one research stage showed significantly favourable mental health outcomes. However, co-creation was rarely extended to later stages (evaluation/dissemination), with few studies specifically with ethnic minority groups. CONCLUSIONS: The co-creation of research may improve several health-related outcomes and public health more broadly, but research is lacking on its longer term effects

Thomas Rotch Receipts for paid bills, 1791-1823

Thomas Newlin is paid $6 for eight days labor on a sheep cote "and for all other demands to this date." 7.45" x 2.25

God's gracious design in inflicting national judgments. A sermon preach'd before the University of Oxford at St Mary's on Friday, Dec. 16th 1720. ... By Thomas Newlin ... [electronic resource].

Electronic reproduction.English Short Title Catalog,Reproduction of original from William Andrews Clark Memorial Library (UCLA)

Assessing the Satisfaction of Citizens Using Teleconsent in Clinical Research

Researchers tested the functionality, and evaluated the feasibility of a telemedicine software, Doxy.me, to complete informed teleconsent sessions remotely with prospective research participants. Twenty healthy volunteers completed a teleconsent session, and web survey assessing overall experience and satisfaction with the Doxy.me software. There was a statistically significant correlation found between age and mean response for the overall reaction category (r = 0.398, p = 0.091) and the systems capabilities category (r = 0.380, p = 0.099). Results suggested that younger users are more satisfied than older users with using teleconsent as a modality for informed consenting. This information will be used to improve the software design and functionality of the Doxy.me software to make the teleconsent experience as simple and intuitive as possible