Chinese medicine, Qijudihuang pill, mediates cholesterol metabolism and regulates gut microbiota in high-fat diet-fed mice, implications for age-related macular degeneration.

Background: Traditional Chinese Medicines have been used for thousands of years but without any sound empirical basis. One such preparation is the Qijudihuang pill (QP), a mixture of eight herbs, that has been used in China for the treatment of various conditions including age-related macular degeneration (AMD), the most common cause of blindness in the aged population. In order to explain the mechanism behind the effect of QP, we used an AMD model of high-fat diet (HFD) fed mice to investigate cholesterol homeostasis, oxidative stress, inflammation and gut microbiota. Methods: Mice were randomly divided into three groups, one group was fed with control diet (CD), the other two groups were fed with high-fat-diet (HFD). One HFD group was treated with QP, both CD and the other HFD groups were treated with vehicles. Tissue samples were collected after the treatment. Cholesterol levels in retina, retinal pigment epithelium (RPE), liver and serum were determined using a commercial kit. The expression of enzymes involved in cholesterol metabolism, inflammation and oxidative stress was measured with qRT-PCR. Gut microbiota was analyzed using 16S rRNA sequencing. Results: In the majority of the lipid determinations, analytes were elevated by HFD but this was reversed by QP. Cholesterol metabolism including the enzymes of bile acid (BA) formation was suppressed by HFD but again this was reversed by QP. BAs play a major role in signaling between host and microbiome and this is disrupted by HFD resulting in major changes in the composition of colonic bacterial communities. Associated with these changes are predictions of the metabolic pathway complexity and abundance of individual pathways. These concerned substrate breakdowns, energy production and the biosynthesis of pro-inflammatory factors but were changed back to control characteristics by QP. Conclusion: We propose that the ability of QP to reverse these HFD-induced effects is related to mechanisms acting to lower cholesterol level, oxidative stress and inflammation, and to modulate gut microbiota.

Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina.

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD.

Engaging Faculty in Shifting Toward Holistic Review: Changing Graduate Admissions Procedures at a Land-Grant, Hispanic-Serving Institution.

Purpose The aim of this tutorial is to share lessons learned from a speech, language, and hearing sciences department at a land-grant, Hispanic-serving institution (HSI) after revising the graduate admissions review process and subsequent discussions related to equity in assessment. This tutorial describes the department as a case example and includes guiding questions that may be helpful for other organizations. Method An adaptive case study approach was used and centered on supporting students at Hispanic-serving institutions. The approach was characterized by structured collaborative reflection throughout the process and engagement of relevant stakeholders at multiple levels. The adaptive method allowed for interim synthesis of stakeholder discussions to inform subsequent phases of the reflection process. Results This tutorial shares critical motivations, barriers, facilitators, and phases that were identified in moving toward holistic evaluation for graduate admissions. Targeted areas for continued improvement related to diversity, equity, and inclusion are described. Conclusions This tutorial outlines lessons learned from changing graduate admissions practices toward holistic review. Self-reflection prompts are provided for institutions and organizations considering changes to their review process. In order to best support diverse communities, increased workforce diversity is needed in the speech, language, and hearing sciences professions, and holistic review practices are recommended as one way to support increased diversity, equity, and inclusion.

Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.

Sensitivity and Specificity of Pure-Tone and Subjective Hearing Screenings Using Spanish-Language Questions.

Purpose The purpose of this study is to determine the sensitivities and specificities of different audiometric hearing screening criteria and single-item and multi-item hearing disability questionnaires among a group of Spanish-speaking adults in a rural community. Method Participants were 131 predominantly older (77% 65+ years) Hispanic/Latinx adults (98%). A structured Spanish-language interview and pure-tone threshold test data were analyzed for each participant. The sensitivities and specificities of three single questions and the Hearing Handicap Index for the Elderly-Screening (HHIE-S; Ventry & Weinstein, 1983) in Spanish, as well as three audiometric screening criteria, were evaluated in relation to the pure-tone threshold test for detecting hearing loss. Results Sensitivity and specificity of audiometric screening criteria varied, but the highest sensitivity was found for the criterion of > 25 dB HL at 1-4 kHz in either ear. The single self-perception question, "¿Cree usted que tiene pérdida de audición? (Do you think you have a hearing loss?)," was shown to be the most sensitive self-report screening compared to other single-item questions and the HHIE-S. This single question was as sensitive as an audiometric screening to detect a moderate hearing loss (> 40 dB HL in either ear). Results from the Spanish HHIE-S indicated poor performance to detect hearing loss in this population, consistent with previous research. Conclusions Among older Spanish-speaking adults, self-reported hearing status had varying sensitivities depending on the question asked. However, of the tools evaluated, the self-perception question proved to be a more sensitive and specific tool than a multi-item screen. Objective audiometric testing (> 25 dB HL) resulted in the highest sensitivity to detect a mild hearing loss.

Hearing care across the life course provided in the community.

Untreated hearing loss is recognized as a growing global health priority because of its prevalence and harmful effects on health and well-being. Until recently, little progress had been made in expanding hearing care beyond traditional clinic-based models to incorporate public health approaches that increase accessibility to and affordability of hearing care. As demonstrated in numerous countries and for many health conditions, sharing health-care tasks with community health workers (CHWs) offers advantages as a complementary approach to expand health-service delivery and improve public health. This paper explores the possibilities of task shifting to provide hearing care across the life course by reviewing several ongoing projects in a variety of settings - Bangladesh, India, South Africa and the United States of America. The selected programmes train CHWs to provide a range of hearing-care services, from childhood hearing screening to management of age-related hearing loss. We discuss lessons learnt from these examples to inform best practices for task shifting within community-delivered hearing care. Preliminary evidence supports the feasibility, acceptability and effectiveness of hearing care delivered by CHWs in these varied settings. To make further progress, community-delivered hearing care must build on established models of CHWs and ensure adequate training and supervision, delineation of the scope of practice, supportive local and national legislation, incorporation of appropriate technology and analysis of programme costs and cost-effectiveness. In view of the growing evidence, community-delivered hearing care may now be a way forward to improve hearing health equity.

La perte de l'acuité auditive non traitée est considérée comme une priorité sanitaire de plus en plus importante à l'échelle mondiale en raison de sa prévalence et de ses effets nocifs sur la santé et le bien-être. Jusqu'à récemment, peu de progrès avaient été accomplis pour développer les soins auditifs en dehors des modèles cliniques traditionnels de façon à intégrer des approches de santé publique permettant d'accroître l'accessibilité, notamment économique, des soins auditifs. Comme cela a été démontré dans de nombreux pays et pour de multiples problèmes de santé, transférer des tâches de soins de santé aux agents sanitaires des collectivités présente des avantages en tant qu'approche complémentaire permettant d'étendre la prestation des services de santé et d'améliorer la santé publique. Cette publication étudie les possibilités de transfert de tâches pour dispenser des soins auditifs tout au long de la vie en examinant plusieurs projets en cours à différents endroits ­ Bangladesh, Inde, Afrique du Sud et États-Unis d'Amérique. Les programmes sélectionnés apprennent aux agents sanitaires des collectivités à dispenser divers services de soins auditifs, du dépistage auditif chez les enfants à la gestion de la perte de l'acuité auditive liée à l'âge. Nous évoquons les leçons tirées de ces exemples pour définir les pratiques optimales concernant le transfert des tâches dans le cadre des soins auditifs dispensés dans des structures de proximité. Les observations préliminaires étayent la faisabilité, l'acceptabilité et l'efficacité des soins auditifs dispensés par les agents sanitaires des collectivités dans ces différents contextes. Pour continuer à progresser, les soins auditifs dispensés dans des structures de proximité doivent s'appuyer sur des modèles éprouvés d'agents sanitaires des collectivités. Il convient par ailleurs d'assurer une formation et une supervision adéquates, de délimiter le champ de pratique, d'adopter une législation locale et nationale favorable, d'intégrer une technologie appropriée et d'analyser les coûts du programme et le rapport coût-efficacité. Compte tenu du nombre croissant d'éléments d'appréciation, les soins auditifs dispensés dans des structures de proximité peuvent désormais constituer une solution pour améliorer l'équité en matière de santé auditive.

La pérdida de audición no tratada se reconoce como una prioridad sanitaria mundial cada vez mayor debido a su prevalencia y a sus efectos perjudiciales para la salud y el bienestar. Recientemente, se había avanzado poco en la expansión de la asistencia auditiva más allá de los modelos tradicionales basados en clínicas para incorporar enfoques de salud pública que aumenten la accesibilidad y asequibilidad de la asistencia auditiva. Como se ha demostrado en numerosos países y para muchas condiciones sanitarias, delegar las tareas de atención sanitaria a los trabajadores sanitarios de la comunidad (CHW) ofrece ventajas como enfoque complementario para ampliar la prestación de servicios sanitarios y mejorar la salud pública. Este documento explora las posibilidades de la delegación de funciones para ofrecer atención auditiva a lo largo de toda la vida mediante la revisión de distintos proyectos en curso en una variedad de entornos: Bangladesh, Estados Unidos de América, India y Sudáfrica. Los programas seleccionados capacitan a los CHW para que ofrezcan una amplia gama de servicios de atención auditiva, desde exámenes auditivos para la infancia hasta el tratamiento de la pérdida de audición relacionada con la edad. Discutimos las lecciones aprendidas de estos ejemplos para informar las mejores prácticas sobre la delegación de funciones dentro de la atención auditiva proporcionada en la comunidad. La evidencia preliminar apoya la factibilidad, aceptabilidad y efectividad de la atención auditiva proporcionada por los CHW en estos variados entornos. Para seguir avanzando, la atención auditiva proporcionada en la comunidad debe basarse en modelos establecidos de los CHW y garantizar una formación y supervisión adecuadas, la delimitación del campo de aplicación, el apoyo de la legislación local y nacional, la incorporación de la tecnología adecuada y el análisis de los costes de los programas y la relación coste-eficacia. En vista de las pruebas cada vez más numerosas, la atención auditiva proporcionada en la comunidad puede ser ahora una solución para mejorar la equidad en la salud auditiva.

Contribution of onset/offset information of modulation to amplitude modulation depth discrimination.

A previous study by [J. Lee, G. Long, and C. Jeung, J. Acoust. Soc. Am. 119, S3332 (2006)] found that information at the onset or offset of modulation could be utilized for improved amplitude modulation (AM) depth discrimination in a continuous carrier condition (carrier presented 250 ms earlier and later than the modulator). In this study, the relative contribution of information at the onset or offset of the modulation was examined with an onset-fringe carrier condition (carrier begins 250 ms earlier than the modulator) and an offset-fringe condition (carrier ends 250 ms later than the modulator). The results suggest that modulation information at the onset might be utilized more than at the offset.