Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b(+) DC-derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase (ALDH) family 1 is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease, used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential, and readily translatable, antifibrotic therapy

Effecting Change and Addressing Inequalities through Community Based Research : Opportunities and Challenges

Access to legal services and pro bono community outreach projects have become embedded in the languages of policymaking and academia over the last few years, and community-based law clinics are beneficial in terms of ensuring ease of access to legal advice and consequent expansion of the number of clients served. The advantage of community justice initiatives is well established in literature and research suggests that they should be participatory, allowing people experiencing problems to play an active role in constructing the solutions. This makes it more likely that individuals will obtain the help they need for the problems they are experiencing, it increases empowerment and encourages them to take preventative action and seek help from competent sources. In February 2024, a team of students and solicitors from Lancaster University’s Law Clinic ran an outreach clinic in Blackpool, which is one of the most deprived areas in the UK. The outreach clinic aimed to reach those most marginalised and disconnected from legal advice and assistance while seeking to understand and identify approaches to bridging the access to justice gap. This paper explores the results of this project, the opportunities, challenges experienced and how they may be overcome in future projects

Somatically ill persons’ self-nominated quality of life domains: review of the literature and guidelines for future studies

OBJECTIVE: To review which domains somatically ill persons nominate as constituting their QoL. Specific objective is to examine whether the method of enquiry affect these domains. METHODS: We conducted two literature searches in the databases PubMed/Medline, CINAHL and Psychinfo for qualitative studies examining patients' self-defined QoL domains using (1) SEIQoL and (2) study-specific questions. For each database, two researchers independently assessed the eligibility of the retrieved abstracts and three researchers subsequently classified all QoL domains. RESULTS: Thirty-six eligible papers were identified: 27 studies using the SEIQoL, and nine presenting data derived from study-specific questions. The influence of the method of enquiry on patients' self-nominated QoL domains appears limited: most domains were presented in both types of studies, albeit with different frequencies. CONCLUSIONS: This review provides a comprehensive overview of somatically ill persons' self-nominated QoL domains. However, limitations inherent to reviewing qualitative studies (e.g., the varying level of abstraction of patients' self-defined QoL domains), limitations of the included studies and limitations inherent to the review process, hinder cross-study comparisons. Therefore, we provide guidelines to address shortcomings of qualitative reports amenable to improvement and to stimulate further improvement of conducting and reporting qualitative research aimed at exploring respondents' self-nominated QoL domains

INVESTIGATION OF CAPITAL ADEQUACY IN TERMS OF DEPT/EQUITY RATIOS OF BUSINESSES TRADED ON THE ISTANBUL STOCK EXCHANGE (BIST) BETWEEN 2009 - 2019

Investors want more information about the company traded on the stock exchange and that the investment they will make will result from analytical decisions. Equity capital adequacy reduces the risk of bankruptcy and concordat of the firm. Therefore, measuring equity capital and determining its adequacy will positively affect economic stability. Factors such as debt levels of companies, cash flow statements, and profit margins on current assets draw attention. This study examined foreign resource distributions and capital adequacy of 32 companies traded in Borsa Istanbul between 2009 and 2019 regarding debt/equity ratios. The company information obtained from BIST has been analyzed for statistical significance. When the relationship between the equity distributions of the enterprises between 2009-2019 was analyzed by correlation analysis, it was determined that there were positive and significant relationships between the data (p≤.05).</jats:p

Developing and managing Bank Service Quality (BSQ) index / Firdaus Abdullah... [et al.]

As the financial landscape evolves dramatically and competition intensifies in the light of current global financial crisis, banking institutions need to respond to the radical change in market needs, and continually reassess their strategies and alternatives. Delivering quality service to customers is seen to be crucial for success and survival in today's competitive banking environment and it is an important route to competitive advantage and corporate profitability. Thus, it is essential to analyze the means of measuring and evaluating the service quality provided by banking institutions as they adjust to the dynamic changes in the environment, and to develop a new measuring tool that forms the basis for capturing the authentic determinants of service quality within the banking sector. However, previous studies have produced scales that bear a resemblance to the generic measures "of service quality, which may not be totally adequate to assess the perceived quality in the banking sector. Therefore, this study aims to design and validate a new measuring instrument of service quality, and ultimately to establish a national service quality index for the banking sector in Malaysia. The new Bank Service Quality Index (BSQ Index) is expected to be an important complement to traditional measures of economic performance, providing useful information to the banking institutions, shareholders, investors, government regulators, and customers. The proposed 29-item instrument has been empirically tested for unidimensionality, reliability and validity using both exploratory and confirmatory factor analysis. A factorial analysis suggests that service quality has three dimensions namely 'Systemization', 'Reliable Communication' and 'Responsiveness', and subsequent multiple regression analysis revealed that 'Systemization' is the most important service quality dimension within the banking sector