Quantitative analysis of estrogen receptor heterogeneity in breast cancer

Immunohistochemical analyses (IHC) of biomarkers are extensively used for tumor characterization and as prognostic and predictive measures. The current standard of single slide analysis assumes that one 5 microM section is representative of the entire tumor. We used our automated image analysis technology (AQUA) using a modified IHC technique with fluorophores to compare estrogen receptor (ER) expression in multiple blocks/slides from cases of primary breast cancer with the objective of quantifying tumor heterogeneity within sections and between blocks. To normalize our ER scores and allow slide-to-slide comparisons, 0.6 microm histospots of representative breast cancer cases with known ER scores were assembled into a 'gold standard array' (GSA) and placed adjacently to each whole section. Overall, there was excellent correlation between AQUA scores and the pathologist's scores and reproducibility of GSA scores (mean linear regression R value 0.8903). Twenty-nine slides from 11 surgical cases were then analyzed totaling over 2000 AQUA images. Using standard binary assignments of AQUA (>10) and pathologist's (>10%) scores as being positive, there was fair concordancy between AQUA and pathologist scores (73%) and between slides from different blocks from the same cases (75%). However using continuous AQUA scores, agreement between AQUA and pathologist was far lower and between slides from different blocks from the same cases only 19%. Within individual slides there was also significant heterogeneity in a scattered pattern, most notably for slides with the highest AQUA scores. In sum, using a quantitative measure of ER expression, significant block-to-block heterogeneity was found in 81% of cases. These results most likely reflect both laboratory-based variability due to lack of standardization of immunohistochemistry and true biological heterogeneity. It is also likely to be dependent on the biomarker analyzed and suggests further studies should be carried out to determine how these findings may affect clinical decision-making processes.     

Household food insecurity and future orientation of Ghanaian youth and their parents

Food insecurity heightens risk for poor mental health and psychosocial functioning. Higher levels of future orientation influence numerous desirable behaviors. However, limited evidence exists on the association between food insecurity and future orientation, particularly in low-resource settings. The objective of this study was to examine the association between food insecurity and future orientation of Ghanaian youth and their parents. The study included a cross-sectional sample of 2656 youth and 2656 parents from 8 of Ghana’s 10 regions. Food insecurity was measured using the Household Food Insecurity Access Scale. Future orientation in the Ghanaian context was measured using three distinct factors adapted from the School Success Profile and the Consideration of Future Consequences scale. We analyzed our data using hierarchical linear modeling, with a three-level linear random-intercept model with covariates. Results suggest an inverse relationship between food insecurity and future orientation of youth and their parents. Food insecurity was consistently and significantly associated with lower orientation toward success (β = ?0.18, 95% confidence interval [CI] = ?0.22, ?0.14) and higher uncertainty of the future (β = 0.22, 95% CI = 0.17, 0.28) among youth, as well as lower consideration of future consequences (β = ?0.15, 95% CI = ?0.23, ?0.06) among parents. Additionally, severe food insecurity was associated with the lowest future orientation scores for youth and their parents. Our findings indicate that, under conditions of food insecurity, youth and their parents lose sight of the future, which may come at a great cost. Encouraging individuals to engage in thinking about the future or to create future images of their selves may not be meaningful if their basic needs, including access to food, are not met. Programs that provide opportunities to generate income and accumulate assets may have a twofold effect of increasing access to food and improving future orientation.     

Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.     

Enhanced antibacterial nanocomposite mats by coaxial electrospinning of polycaprolactone fibers loaded with Zn-based nanoparticles

ZnO and Zn acetate nanoparticles were embedded in polycaprolactone coaxial-fibers and uniaxial-fibers matrices to develop potential antibacterial nanocomposite wound dressings (mats). Morphology, composition, wettability, crystallinity and fiber structure of mats were characterized. Antibacterial properties of mats were tested against E. coli and S. aureus by turbidity and MTT assays. The effect of UVA illumination (prior to bacteria inoculation) on mats’ antibacterial activity was also studied. Results showed that a coaxial-fibers design maintained nanoparticles distributed in the outer-shell of fibers and, in general, enhanced the antibacterial effect of the mats, in comparison to conventional uniaxial-fibers mats. Results indicated that mats simultaneously inhibited planktonic and biofilm bacterial growth by, probably, two main antibacterial mechanisms; 1) release of Zn²⁺ ions (mainly from Zn acetate nanoparticles) and 2) photocatalytic oxidative processes exerted by ZnO nanoparticles. Antibacterial properties of mats were significantly improved by coaxial-fibers design and exposure to UVA-light prior to bacteria inoculation.     

<Emphasis Type="Italic">Care Coordination: Empowering Families</Emphasis>, a Promising Practice to Facilitate Medical Home Use Among Children and Youth with Special Health Care Needs

Introduction This paper describes the care coordination training program and results of an evaluation from its pilot in seven states. Despite the importance of practice-based care coordination, only 42.3% of children with special health care needs (CYSHCN) met all needed components of care coordination as defined by the Maternal Child Health Bureau. Recognizing that children with medically complex conditions often have lower rates of achieving care coordination within a medical home, the Region 4 Midwest Genetics Collaborative worked with families to develop a training to empower families in care coordination. The Care Coordination: Empowering Families(CCEF) training provides families with the knowledge, tools, and resources to engage with health, education and family support systems. This article gives an overview of the training and comprehensive evaluation. Methods Participants were family caregivers of children with genetic conditions and other special health care needs recruited in one of seven pilot states. Evaluation data were collected from 190 participants prior to and immediately following the training. An additional follow-up assessment one full year post training was completed by 80 participants (a response rate of 42%). Results Families who attended the training report being the primary source of care coordination for their children and 83.7% see their role in their child’s healthcare changing as a result of the training. The findings suggest that peer support and communication with providers increased as a result of the training over the course of the study. The data suggest that the training impacted how the family interacts with the child’s doctor, including initiating conversations to prepare their child for transition to adult health care. Further, families report system-level improvements 1 year later compared to the pre-training assessment. Discussion CCEF training is a promising practice for facilitating medical home use among CYSHCN.     

Reduced Anxiety in Forensic Inpatients after a Long-Term Intervention with Atlantic Salmon

The aim of the present study was to investigate the effects of Atlantic salmon consumption on underlying biological mechanisms associated with anxiety such as heart rate variability (HRV) and heart rate (HR) as well as a measure of self-reported anxiety. Moreover, these biological and self-reported outcome measures were investigated in relation to specific nutrients; vitamin D status, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Ninety-five male forensic inpatients were randomly assigned into a Fish (Atlantic salmon three times per week from September to February) or a Control group (alternative meal, e.g., chicken, pork, or beef three times per week during the same period). HRV measured as the root mean square of successive differences (rMSSD), HR, state- and trait-anxiety (STAI), were assessed before (pre-test) and at the end of the 23 weeks dietary intervention period (post-test). The Fish group showed significant improvements in both rMSSD and HR. The Fish group also showed significant decreases in state-anxiety. Finally, there was a positive relationship between rMSSD and vitamin D status. The findings suggest that Atlantic salmon consumption may have an impact on mental health related variables such as underlying mechanisms playing a key role in emotion-regulation and state-anxiety.