Self-Disgust within Eating Disordered Groups: Associations with Anxiety, Disgust Sensitivity and Sensory Processing.

This study aimed to assess the relationship between self-disgust and sensory processing within eating psychopathology. Five hundred and ninety-one women with a self-reported diagnosis of anorexia nervosa, bulimia nervosa or who had no previous history of an eating disorder completed a battery of online questionnaires measuring disgust, emotion and sensory variables. Those with an eating disorder reported significantly higher rates of self-disgust than those with no history of disordered eating. In groups of women with self-reported bulimia, self-disgust was associated with sensation avoidance and sensation seeking. Within the group with anorexia nervosa, self-disgust was associated with low registration and sensation seeking. This report is the first to examine the expression of the emotion self-disgust within eating psychopathology and examine associations of this factor with sensory processing. The emotion self-disgust needs to be further examined to understand its possible role in the onset and maintenance of disordered eating. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Quantitation of fixative-induced morphologic and antigenic variation in mouse and human breast cancers.

Quantitative Image Analysis (QIA) of digitized whole slide images for morphometric parameters and immunohistochemistry of breast cancer antigens was used to evaluate the technical reproducibility, biological variability, and intratumoral heterogeneity in three transplantable mouse mammary tumor models of human breast cancer. The relative preservation of structure and immunogenicity of the three mouse models and three human breast cancers was also compared when fixed with representatives of four distinct classes of fixatives. The three mouse mammary tumor cell models were an ER+/PR+ model (SSM2), a Her2+ model (NDL), and a triple negative model (MET1). The four breast cancer antigens were ER, PR, Her2, and Ki67. The fixatives included examples of (1) strong cross-linkers, (2) weak cross-linkers, (3) coagulants, and (4) combination fixatives. Each parameter was quantitatively analyzed using modified Aperio Technologies ImageScope algorithms. Careful pre-analytical adjustments to the algorithms were required to provide accurate results. The QIA permitted rigorous statistical analysis of results and grading by rank order. The analyses suggested excellent technical reproducibility and confirmed biological heterogeneity within each tumor. The strong cross-linker fixatives, such as formalin, consistently ranked higher than weak cross-linker, coagulant and combination fixatives in both the morphometric and immunohistochemical parameters.

Successful partnerships with third sector organisations to enhance the healthcare student experience: a partnership evaluation.

There is limited research surrounding academic partnerships and more research is needed to educate universities, and the private, public and third sectors about the benefits and limitations of such partnerships. The aim of this study was to outline the unique partnership between Macmillan Cancer Support and De Montfort University and to evaluate the progress of this partnership. A qualitative approach was employed which involved interviews with nine members of the partnership's steering group. Interviews were transcribed and analysed using thematic analysis. The results showed that a partnership between a university and a third sector charity can have mutual benefits for all those involved, particularly for students and those affected by cancer. Furthermore, the module to develop volunteering among families affected cancer, created through this partnership is now being considered by other universities as a way of providing holistic and non-traditional lecture based learning experiences. Recommendations are made for future partnerships between third sector charities and universities.

Reliability and relevance of radiographic measures of metatarsus primus elevatus and arch alignment in individuals with midfoot arthritis and controls.

BACKGROUND: Low arch alignment and metatarsus primus elevatus (MPE) have been postulated to increase dorsal compressive stresses in the joints of the medial column of the foot and to contribute to the development of degenerative changes. The primary purposes of this study were (1) to examine the relationship between radiographic measures of arch alignment and MPE and (2) to assess arch alignment and MPE in individuals with midfoot arthritis and in asymptomatic controls. The secondary aim was to examine the reliability of radiographic measures of arch alignment and MPE. METHODS: Radiographic measures of arch height and MPE were quantified on 28 individuals with midfoot arthritis and 22 individuals in a control group. Reliability was assessed using the intraclass correlation coefficient (ICC). The Pearson product moment correlation (r) was used to assess the relationship between arch alignment and MPE. Between-group differences were assessed using a two-sample t test (α = 0.05). RESULTS: Good to excellent reliability was noted for measures of arch height (ICC[2,3] = 0.919-0.994) as well as MPE (ICC[2,3] = 0.891-0.882). A modest positive association was noted between normalized cortical elevation and normalized navicular height (r = 0.274, P = .030) and calcaneal inclination angle (r = 0.263, P = .035). Individuals with midfoot arthritis demonstrated lower arch alignment, reflected in a significantly higher calcaneal-first metatarsal angle (P = .002), lower calcaneal inclination angle (P = .004), and lower normalized navicular height (P < .001) compared with controls. No evidence was found to support between-group differences in lateral intermetatarsal angle (P = .495) and normalized cortical elevation (P = .146). CONCLUSIONS: These findings provide objective data establishing the reliability of measures of MPE and arch alignment and their potential clinical significance.

L-BLP25 vaccine plus letrozole induces a TH1 immune response and has additive antitumor activity in MUC1-expressing mammary tumors in mice.

PURPOSE: In this study, we examine the immunomodulatory effects and antitumor activity of tamoxifen and letrozole when combined with the human epithelial mucin (hMUC1)-specific vaccine, L-BLP25, in the hMUC1-expressing mammary tumor (MMT) mouse model. EXPERIMENTAL DESIGN: Dose-finding studies were conducted for both tamoxifen and letrozole. Letrozole and L-BLP25 combination studies used 69 MMT female mice assigned to five groups: untreated, cyclophosphamide + placebo, cyclophosphamide + L-BLP25, letrozole 0.8 mg/kg, and cyclophosphamide + L-BLP25 + letrozole. Tamoxifen and L-BLP25 combination studies used 48 MMT female mice assigned to five treatment groups: untreated, cyclophosphamide + placebo, cyclophosphamide + L-BLP25, tamoxifen 50 mg/kg, and cyclophosphamide + L-BLP25 + tamoxifen 50 mg/kg group. Mice were injected subcutaneously with L-BLP25 (10 µg) weekly for 8 weeks. Serum cytokines were serially measured using a Luminex assay, whereas splenocytes at termination were analyzed by ELISpot to determine T-helper (T(H))1/T(H)2 polarization of immune response. RESULTS: Daily oral doses of 50 and 0.8 mg/kg of tamoxifen and letrozole, respectively, resulted in a significant survival advantage over controls (P < 0.05). A predominant T(H)1-polarized immune response in vaccinated mice was seen with or without tamoxifen or letrozole treatments. In the L-BLP25 plus letrozole treatment group, statistically significant (P < 0.05) additive antitumor activity was observed, whereas tamoxifen plus L-BLP25 was not significantly different (P > 0.05). CONCLUSION: The results of this study show that hormonal therapy does not interfere with L-BLP25-induced predominant T(H)1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.

Ospemifene and 4-hydroxyospemifene effectively prevent and treat breast cancer in the MTag.Tg transgenic mouse model.

OBJECTIVE: Ospemifene, a new drug indicated for the treatment of vulvovaginal atrophy, has completed phase III clinical trials. A condition affecting millions of women worldwide, vulvovaginal atrophy has long been treated with estrogen therapy. Estrogen treatment carries with it risks of thromboembolism, endometrial proliferative effects, and breast cancer promotion. In this study, we test the effects of three dosing levels of ospemifene in both the prevention and treatment of breast cancer in the MTag.Tg mouse model. METHODS: The polyomavirus middle-T transgenic mouse model (MTag.Tg), which produces synchronized, multifocal mammary tumors in the immunologically intact C57BL/6 background, was used to examine the impact of ospemifene treatment. First, a cell line derived from an MTag.Tg mouse tumor (MTag 34) was treated in vitro with ospemifene and its major metabolite, 4-hydroxyospemifene (4-OH ospemifene). MTag.Tg mice were treated daily by gavage with three different doses of ospemifene (5, 25, and 50 mg/kg) before or after the development of mammary tumors. Survival and tumor development results were used to determine the effect of ospemifene treatment on mammary tumors in both the preventive and treatment settings. RESULTS: Tumors and the MTag 34 cell line were positive for estrogen receptor expression. The MTag 34 line was not stimulated by ospemifene or its major, active metabolite 4-OH ospemifene in vitro. Ospemifene increased survival time and exerted an antitumor effect on the development and growth of estrogen receptor-positive mammary tumors in the MTag.Tg mouse model at the 50-mg/kg dose. The levels of ospemifene and 4-OH ospemifene in both the tumors and plasma of mice confirmed the dosing. Ospemifene did not exert an estrogenic effect in the breast tissue at doses equivalent to human dosing. CONCLUSIONS: Ospemifene prevents and treats estrogen receptor-positive MTag.Tg mammary tumors in this immune-intact mouse model in a dose-dependent fashion. Ospemifene drug levels in the plasma of treated mice were comparable with those found in humans. Combined with our previous data, ospemifene does not seem to pose a breast cancer risk in animals and slows down cancer development and progression in the MTag.Tg model.

Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.

Breast cancers with a basal-like gene signature are primarily triple-negative, frequently metastatic, and carry a poor prognosis. Basal-like breast cancers are enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT). While EMT is generally thought to be important in the process of metastasis, in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triple-negative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence suggestive of phenotypic plasticity in the patient. The DKAT cell line displays a basal-like phenotype in vitro when cultured in serum-free media, and undergoes phenotypic changes consistent with EMT/MET in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. DKAT cells also express progenitor-cell markers, and single DKAT cells are able to generate tumorspheres containing both epithelial and mesenchymal cell types. In vivo, as few as ten DKAT cells are capable of forming xenograft tumors which display a range of epithelial and mesenchymal phenotypes. The DKAT model provides a novel model to study the molecular mechanisms regulating phenotypic plasticity and the aggressive biology of triple-negative breast cancers.