Mouse Middle Ear Ion Homeostasis Channels and Intercellular Junctions

The middle ear contains homeostatic mechanisms that control the movement of ions and fluids similar to those present in the inner ear, and are altered during inflammation.The normal middle ear cavity is fluid-free and air-filled to allow for effective sound transmission. Within the inner ear, the regulation of fluid and ion movement is essential for normal auditory and vestibular function. The same ion and fluid channels active in the inner ear may have similar roles with fluid regulation in the middle ear.Middle and inner ears from BALB/c mice were processed for immunohistochemistry of 10 specific ion homeostasis factors to determine if similar transport and barrier mechanisms are present in the tympanic cavity. Examination also was made of BALB/c mice middle ears after transtympanic injection with heat-killed Haemophilus influenza to determine if these channels are impacted by inflammation.The most prominent ion channels in the middle ear included aquaporins 1, 4 and 5, claudin 3, ENaC and Na(+),K(+)-ATPase. Moderate staining was found for GJB2, KCNJ10 and KCNQ1. The inflamed middle ear epithelium showed increased staining due to expected cellular hypertrophy. Localization of ion channels was preserved within the inflamed middle ear epithelium.The middle ear epithelium is a dynamic environment with intrinsic mechanisms for the control of ion and water transport to keep the middle ear clear of fluids. Compromise of these processes during middle ear disease may underlie the accumulation of effusions and suggests they may be a therapeutic target for effusion control

Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96363/1/j.1748-720X.2012.00703.x.pd

Can the concept of Health Promoting Schools help to improve students' health knowledge and practices to combat the challenge of communicable diseases: Case study in Hong Kong?

<p>Abstract</p> <p>Background</p> <p>The growing epidemics of emerging infectious diseases has raised the importance of a setting approach and include the Health Promoting School (HPS) framework to promote better health and hygiene. Built on the concept of 'the' HPS framework, the Hong Kong Healthy Schools Award scheme includes "Personal Health Skills" as one of its key aspects to improve student hygiene knowledge and practices. This study examines the differences in student perceptions, knowledge and health behaviours between those schools that have adopted the HPS framework and those that have not adopted.</p> <p>Methods</p> <p>A cross-sectional study using multi-stage random sampling was conducted among schools with awards (HSA) and those schools not involved in the award scheme nor adopting the concept of HPS (non-HPS). For HSA group, 5 primary schools and 7 secondary schools entered the study with 510 students and 789 students sampled respectively. For the 'Non-HPS' group, 8 primary schools and 7 secondary schools entered the study with 676 students and 725 students sampled respectively. A self-administered questionnaire was used as the measuring instrument.</p> <p>Results</p> <p>Students in the HSA category were found to be better with statistical significance in personal hygiene practice, knowledge on health and hygiene, as well as access to health information. HSA schools were reported to have better school health policy, higher degrees of community participation, and better hygienic environment.</p> <p>Conclusion</p> <p>Students in schools that had adopted the HPS framework had a more positive health behaviour profile than those in non-HPS schools. Although a causal relationship is yet to be established, the HPS appears to be a viable approach for addressing communicable diseases.</p

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Ion Channels.

<p>A: ENaC in the inner ear occurred in the apical membrane of the crista ampullaris, as well as other places. B: Na+,K+-ATPase staining in the inner ear stained the stria vascularis, fibrocytes of the spiral ligament, and the organ of Corti. C: ENaC in the middle ear was located in the apical membrane of the epithelium. D: Na⁺,K⁺-ATPase middle ear diffusely stained the lining epithelium. E: KCNQ1 of the inner ear occurred at the apical surface of marginal cells of stria vascularis. F: KCNJ10 in the inner ear was seen, staining the intermediate cells of stria vascularis and organ of Corti. G: KCNQ1 stained the middle ear epithelium. H: KCNJ10 also stained the middle ear epithelium. Negative controls are displayed as inset pictures. [CA, crista ampullaris; SV, stria vascularis; SM, scala media; SL, spiral limbus; RM, Reissner’s membrane; OC, organ of Corti; MEE, middle ear epithelium; MES, middle ear space].</p

Aquaporins.

<p>Aquaporins 1, 4, and 5 in the inner ear (A-C) and middle ear (D-G). A: AQP1 in the inner ear showed positive staining of the lateral lining of the spiral ligament and some fibrocytes within the spiral ligament. B: AQP4 in the inner ear positively stained bone of the otic capsule, organ of Corti, and spiral ganglion. C: AQP5 showed mild labeling of the inner ear organ of Corti. D: AQP 1 antibody stained the middle ear epithelial submucosa and capillary endothelium. E and F: Middle ear AQP4 labeled the middle ear epithelium itself and portions of the ossicular bones, malleus and incus. G: AQP5 in the middle ear appeared limited to the apical membranes of the epithelium. Negative controls are displayed as inset pictures. [SV, stria vascularis; SM, scala media; SL, spiral ligament; RM, Reissner’s membrane; OC, organ of Corti; ST scala tympani; MEE, middle ear epithelium; SUB, submucosa; MES, middle ear space; M, malleus; I, incus].</p

Ion homeostasis gene expression for the control animals that received no treatment three hours and six hours after transtympanic inoculation with <i>H flu</i>.

<p>This reflects fold change in gene expression seven and ten hours after inoculation compared to animals receiving no bacteria. Although there were some genes that were expressed at higher than normal levels (claudin 4, gap junction a1, aquaporin 1), the majority of homeostasis genes in the middle ear were suppressed in expression. Many other genes were reduced to 10–30% of normal expression (Clcnka, claudin 14, aquaporins 2 and 3, most postassiumchannels, and ENac channels Scnn1b and Scnn1g), but these did not reach statistical significance due to variability. In general, the expression levels seen in the three hour controls were similar to those in the six hour controls.</p

Impact of steroid treatment on ion homeostasis gene expression.

<p>Mice received either prednisolone (Pred) or aldosterone (Aldo) three hours after after transtympanic inoculation with <i>H flu</i> and harvested four hours later (total seven hours post inoculation). With the exception of Gja1, Aqp1, and Tmprss3, most of the genes controlling ion and fluid balances were upregulated by the steroids.</p

Comparison of treatments on cytokine gene expression.

<p>A comparison was made of untreated controls, <i>H flu</i> only mice, and the two steroid treatments to determine how effective the steroids were is returning homeostasis genes back to a normal level. Claudin 4 was upregulated by <i>H flu</i> and its levels were not reduced by the steroids. The remaining genes were significantly up or down regulated by the <i>H flu</i> treatment, and steroid treatments returned expression of these genes back to normal levels.</p