Pubertal high fat diet: effects on mammary cancer development

INTRODUCTION: Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. METHODS: Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. RESULTS: HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages. CONCLUSIONS: Taken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD

Ethical issues in image-based research

This paper provides an overview of current ethical concerns in image-based research. It considers the influence of institutional structures such as regulatory frameworks, professional guidelines and institutional review boards before focusing on issues of data collection and dissemination. The paper discusses informed consent, anonymity and confidentiality, specifically in relation to how they may differ in image-based compared to word-based research. It is suggested that a situated approach to image-based ethics is better able to take account of the concrete, everyday situations within which ethics are negotiated between researchers and research participants

Rigid versus semi-rigid orthotic use following TMC arthroplasty : a randomized controlled trial

Introduction: The trapeziometacarpal (TMC) joint of the human thumb is the second most common joint in the hand affected by osteoarthritis. TMC arthroplasty is a common procedure used to alleviate symptoms. No randomized controlled trials have been published on the efficacy of different post-operative orthotic regimes. Method: Fifty six participants who underwent TMC arthroplasty were allocated to either rigid orthotic or semi-rigid orthotic groups. Both groups started an identical exercise program at two weeks following surgery. Outcome measures were assessed by an assessor blinded to group allocation. The primary outcome was the Patient Rated Wrist and Hand Evaluation (PRWHE) and secondary outcomes included the Michigan Hand Questionnaire (MHQ), thumb palmar abduction, first metacarpophalangeal extension and three point pinch grip. Measures were taken pre-operatively, at six weeks, three months and one year post-operatively. Between-group differences were analyzed with linear regression. Results: Both groups performed equally well. There was no significant between-group difference for PRWHE scores (0.47, CI −11.5 to 12.4), including subscales for pain and function, or for any of the secondary outcomes at one year follow-up. Conclusion: We found no difference in outcomes between using a rigid or semi-rigid orthosis after TMC arthroplasty. Patient comfort, cost and availability may determine choice between orthoses in clinical practice.7 page(s

Prognosis and prognostic factors for patients with persistent wrist pain who proceed to wrist arthroscopy

Wrist pain is common. People with persistent pain commonly undergo arthroscopic investigation. Little is known about the prognosis or prognostic factors for these patients. The purpose of the study was to evaluate prognosis and prognostic factors for pain and functional disability in patients with persistent wrist pain who proceed to arthroscopic investigation. The study design used was a prospective cohort study. One hundred and five consecutive participants who underwent arthroscopic investigation for undiagnosed wrist pain for at least four-week duration were recruited. Patient-rated wrist and hand evaluation (PRWHE) scores were determined at baseline (before arthroscopy) and one year after arthroscopy. One-year follow-up data were obtained for 97 (92%) of 105 participants. Mean PRWHE total score declined from 49 of 100 (standard deviation [SD] 18.5) at baseline to 26 of 100 (SD 20.4) at one year. Two prognostic factors were identified: baseline PRWHE and duration of symptoms. These factors explained 19% and 5% of the variability in the final PRWHE score, respectively. Results of provocative wrist tests and arthroscopic findings did not significantly contribute to prognosis in this cohort. This study provides the first robust evidence of the prognosis of persistent wrist pain. Participants who underwent arthroscopic investigation for persistent wrist pain improved on average by approximately 50% at one year; however, most continued to have some pain and disability. Duration of pain and PRWHE at baseline explained 24% of the one-year PRWHE score. Level of Evidence: Level 2.6 page(s

The relationship between duration of untreated psychosis and outcome: an eight-year prospective study.

Longer duration of untreated psychosis (DUP) prior to the initiation of treatment has been found to predict poorer short-term clinical and functional outcomes in patients with first-episode psychosis (FEP). The extent to which the relationship between DUP and outcome is maintained in the medium-to-long term however remains unclear. We examined the influence of DUP on clinical and functional outcomes in a prospective, naturalistic study of 318 FEP patients followed up 8 years after initial treatment at a specialist early psychosis service. Quality of life, social and occupational functioning, positive and negative symptoms at 8 years were assessed using standardized instruments. Multiple linear regression analyses indicated that, after controlling for the effects of other factors, shorter DUP correlated moderately with decreased severity of positive symptoms, and enhanced social and occupational functioning and quality of life. There was no uniform point associated with medium-to-long term impairment, with some domains of outcome more sensitive to treatment delay than others. However a consistent finding was that outcomes for these domains were significantly worse when DUP exceeded 3 months. Among those with a schizophrenia-spectrum diagnosis, DUP exceeding 1 year was associated with poorer outcome. No association was found between DUP and negative symptoms in either diagnostic group. As with short-term prognosis, DUP appears to be an independent predictor of prognosis in the medium-to-long term. Results support the need for assertive early detection strategies to facilitate the timely delivery of effective intervention programs to those with emerging psychotic illness in order to reduce the risk of long term deleterious outcomes