Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy.

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg×4); 131I- (1mCi or 2×0.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-

Towards a functional model of mental disorders incorporating the laws of thermodynamics

The current paper presents the hypothesis that the understanding of mental disorders can be advanced by incorporating the laws of thermodynamics, specifically relating to energy conservation and energy transfer. These ideas, along with the introduction of the notion that entropic activities are symptomatic of inefficient energy transfer or disorder, were used to propose a model of understanding mental ill health as resulting from the interaction of entropy, capacity and work (environmental demands). The model was applied to Attention Deficit Hyperactivity Disorder, and was shown to be compatible with current thinking about this condition, as well as emerging models of mental disorders as complex networks. A key implication of the proposed model is that it argues that all mental disorders require a systemic functional approach, with the advantage that it offers a number of routes into the assessment, formulation and treatment for mental health problems

Inclusive Masculinity in a Fraternal Setting

This ethnographic research uses thirty-two in-depth interviews and two years of par-ticipant observation on a large chapter of a national fraternity to examine the construc-tion of masculinity among heterosexual men. Whereas previous studies of masculine construction maintain that most men in fraternities attempt to bolster their masculinity through the approximation of requisites of hegemonic masculinity, this research shows that there also exists a more inclusive form of masculinity institutionalized in the fra-ternal system: one based on social equality for gay men, respect for women, and racial parity and one in which fraternity men bond over emotional intimacy

Allied Health Professional Support in Pediatric Inflammatory Bowel Disease: A Survey from the Canadian Children Inflammatory Bowel Disease Network—A Joint Partnership of CIHR and the CH.I.L.D. Foundation

Objectives. The current number of healthcare providers (HCP) caring for children with inflammatory bowel disease (IBD) across Canadian tertiary-care centres is underinvestigated. The aim of this survey was to assess the number of healthcare providers (HCP) in ambulatory pediatric IBD care across Canadian tertiary-care centres. Methods. Using a self-administered questionnaire, we examined available resources in academic pediatric centres within the Canadian Children IBD Network. The survey evaluated the number of HCP providing ambulatory care for children with IBD. Results. All 12 tertiary pediatric gastroenterology centres participating in the network responded. Median full-time equivalent (FTE) of allied health professionals providing IBD care at each site was 1.0 (interquartile range (IQR) 0.6–1.0) nurse, 0.5 (IQR 0.2–0.8) dietitian, 0.3 (IQR 0.2–0.8) social worker, and 0.1 (IQR 0.02–0.3) clinical psychologists. The ratio of IBD patients to IBD physicians was 114 : 1 (range 31 : 1–537 : 1), patients to nurses/physician assistants 324 : 1 (range 150 : 1–900 : 1), dieticians 670 : 1 (range 250 : 1–4500 : 1), social workers 1558 : 1 (range 250 : 1–16000 : 1), and clinical psychologists 2910 : 1 (range 626 : 1–3200 : 1). Conclusions. There was a wide variation in HCP support among Canadian centres. Future work will examine variation in care including patients’ outcomes and satisfaction across Canadian centres

Diagnostic Delay Is Associated with Complicated Disease and Growth Impairment in Paediatric Crohn\u27s Disease

Background: Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. Methods: We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis \u3e75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. Results: Overall (64% Crohn\u27s disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was \u3e9.2 months; in CD, \u3e10.8 months and in UC/IBD-U, \u3e6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. Conclusions: Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD

5-fluorouracil and hydroxyurea enhance adenovirus-mediated transgene expression in colon and hepatocellular carcinoma cells

To investigate the efficient transduction of tumor cells which remains a major limitation of cancer gene therapy..Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47535/1/432_2004_Article_608.pd

Can constructive deviance be empowered? A multi-level field study in Australian supermarkets

We test four hypotheses about how leaders facilitate constructive deviance in the teams they manage. Constructive deviance describes ways of creating value by departing from common ways of working. We test a multi-level model that suggests links between various leadership behaviors, psychological empowerment, and constructive deviance at the individual and team levels. Our findings add nuance to the prevalent assumption that empowered employees engage in more constructive deviance than unempowered employees do by suggesting that, rather than stimulating constructive deviance, empowerment makes deviance unnecessary. We detail implications for management