Image Analysis-Based Approaches for Scoring Mouse Models of Colitis.

Mouse models of inflammatory bowel disease are critical for basic and translational research that is advancing the understanding and treatment of this disease. Assessment of these mouse models frequently relies on histologic endpoints. In recent years, whole slide imaging and digital pathology-based image analysis platforms have become increasingly available for implementation into the pathology workflow. These automated image analysis approaches allow for nonbiased quantitative assessment of histologic endpoints. In this study, the authors sought to develop an image analysis workflow using a commercially available image analysis platform that requires minimal training in image analysis or programming, and this workflow was used to score 2 mouse models of colitis that are primarily characterized by immune cell infiltrates in the lamina propria. Although the software was unable to accurately and consistently segment hematoxylin and eosin-stained sections, automated quantification of CD3 immunolabeling resulted in strong correlations with the pathologist's score in all studies and allowed for the identification of 8 of the 9 differences among treatment groups that were identified by the pathologist. These results demonstrate not only the ability to incorporate solutions based on image analysis into the pathologist's workflow but also the importance of immunohistochemical or histochemical surrogates for the incorporation of image analysis in histologic assessments.

An Internet-based program to enhance motivation to change in females with symptoms of an eating disorder: a randomized controlled trial.

BACKGROUND: Previous research has demonstrated an association between low motivation to change and an unfavorable treatment outcome in patients with an eating disorder. Consequently, various studies have examined the effects of motivational enhancement therapy (MET) on motivation to change and treatment outcome in eating disorders. In each of these studies, MET was administered in a face-to-face setting. However, because of its anonymity and ease of access, the internet provides several advantages as the format for such an intervention. Therefore, the current study investigated the effects of an internet-based program ('ESS-KIMO') to enhance motivation to change in eating disorders. METHOD: In total, 212 females were accepted for participation and assigned randomly to the intervention condition (n = 103) or waiting-list control condition (n = 109). The intervention consisted of six online MET sessions. Before and after the intervention or waiting period respectively, participants completed the Eating Disorder Examination Questionnaire (EDE-Q), the Stages of Change Questionnaire for Eating Disorders (SOCQ-ED), the Pros and Cons of Eating Disorders Scale (P-CED), the Self-Efficacy Scale (SES), and the Rosenberg Self-Esteem Scale (RSES). A total of 125 participants completed the assessment post-treatment. Completer analyses and intent-to-treat analyses were performed. RESULTS: Significant time × group interactions were found, indicating a stronger increase in motivational aspects and self-esteem, in addition to a stronger symptom reduction on some measures from pre- to post-treatment in the intervention group compared to the control group. CONCLUSIONS: Internet-based approaches can be considered as useful for enhancing motivation to change in eating disorders and for yielding initial symptomatic improvement.

Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models.

Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice its involvement in human cancer is not well characterized. Here we report that FGF19 and its cognate receptor FGF receptor 4 (FGFR4) are coexpressed in primary human liver, lung and colon tumors and in a subset of human colon cancer cell lines. To test the importance of FGF19 for tumor growth, we developed an anti-FGF19 monoclonal antibody that selectively blocks the interaction of FGF19 with FGFR4. This antibody abolished FGF19-mediated activity in vitro and inhibited growth of colon tumor xenografts in vivo and effectively prevented hepatocellular carcinomas in FGF19 transgenic mice. The efficacy of the antibody in these models was linked to inhibition of FGF19-dependent activation of FGFR4, FRS2, ERK and beta-catenin. These findings suggest that the inactivation of FGF19 could be beneficial for the treatment of colon cancer, liver cancer and other malignancies involving interaction of FGF19 and FGFR4.

Glycosylation of immunodominant linear epitopes in the carboxy-terminal region of the caprine arthritis-encephalitis virus surface envelope enhances vaccine-induced type-specific and cross-reactive neutralizing antibody responses.

This study evaluated type-specific and cross-reactive neutralizing antibodies induced by immunization with modified surface glycoproteins (SU) of the 63 isolate of caprine arthritis-encephalitis lentivirus (CAEV-63). Epitope mapping of sera from CAEV-infected goats localized immunodominant linear epitopes in the carboxy terminus of SU. Two modified SU (SU-M and SU-T) and wild-type CAEV-63 SU (SU-W) were produced in vaccinia virus and utilized to evaluate the effects of glycosylation or the deletion of immunodominant linear epitopes on neutralizing antibody responses induced by immunization. SU-M contained two N-linked glycosylation sites inserted into the target epitopes by R539S and E542N mutations. SU-T was truncated at 518A, upstream from the target epitopes, by introduction of termination codons at 519Y and 521Y. Six yearling Saanen goats were immunized subcutaneously with 30 microg of SU-W, SU-M, or SU-T in Quil A adjuvant and boosted at 3, 7, and 16 weeks. SU antibody titers determined by indirect enzyme-linked immunosorbent assay demonstrated anamnestic responses after each boost. Wild-type and modified SU-induced type-specific CAEV-63 neutralizing antibodies and cross-reactive neutralizing antibodies against CAEV-Co, a virus isolate closely related to CAEV-63, and CAEV-1g5, an isolate geographically distinct from CAEV-63, were determined. Immunization with SU-T resulted in altered recognition of SU linear epitopes and a 2.8- to 4.6-fold decrease in neutralizing antibody titers against CAEV-63, CAEV-Co, and CAEV-1g5 compared to titers of SU-W-immunized goats. In contrast, immunization with SU-M resulted in reduced recognition of glycosylated epitopes and a 2.4- to 2.7-fold increase in neutralizing antibody titers compared to titers of SU-W-immunized goats. Thus, the glycosylation of linear immunodominant nonneutralization epitopes, but not epitope deletion, is an effective strategy to enhance neutralizing antibody responses by immunization.