A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Parent-children discrepancies in the assessment of children’s and adolescents’ happiness

In this study we assessed parent-child agreement in the perception of a child’s general happiness or well-being in typically developing children (10-11 years-olds; N = 172) and adolescents (15-16 years-olds; N = 185). Despite parent and child reporters providing internally consistent responses in the General Happiness single-item scale and the Oxford Happiness Questionnaire-short form, their perceptions about children’s and adolescents’ general happiness did not correlate. Parents of 10-11 year-olds significantly overestimated children’s happiness, supporting previous literature on the parents’ positivity bias effect. However, parents of 15-16 year-olds showed the reverse pattern, as they underestimated adolescents’ happiness. Furthermore, parents’ self-reported happiness or well-being (reported six months later) significantly correlated with their estimations of children’s and adolescents’ happiness. Therefore, these results suggest a potential parents’ egocentric bias when estimating their children’s happiness. These findings are discussed in terms of their theoretical and applied implications for research into child-parent relationships

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the Breast Cancer Quality of Care Study (BQUAL)

Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p \u3c 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence

Correction to: The International/Canadian Hereditary Angioedema Guideline

An amendment to this paper has been published and can be accessed via the original article.Medicine, Faculty ofNon UBCAllergy and Immunology, Division ofMedicine, Department ofReviewedFacult