This study investigated the potential of adalimumab (ADA), a monoclonal antibody targeting TNF-alfa, to protect the inner ear from intense sound exposure, given that inflammatory cytokines, including TNF-alfa, are linked to hearing loss in acoustic disorders. In this study, adalimumab was administered to mice, and its effect on the inner ear was assessed. We examined the translocation of ADA to the inner ear and its ototoxicity and impact on acoustic exposure. The results showed that adalimumab partially reached the cochlea after administration but increased the susceptibility to acoustic exposure, resulting in higher hair cell loss in the inner ear. While TNF-alfa had been considered a potential therapeutic target, the results suggested that excessive TNF-alfa suppression could harm the inner ear. We acknowledged some limitations, such as the use of adalimumab instead of an anti-mouse TNF-alfa antibody and the need to explore the suppression of other cytokines for better inner ear protection. In conclusion, adalimumab administration was found to increase the inner earʼs susceptibility to acoustic exposure, potentially leading to more significant hair cell damage, possibly due to excessive TNF-alfa suppression.

Vestibular hair cells are susceptible to damage from various stimuli such as infections, ischemia, and certain therapeutic drugs, including aminoglycoside antibiotics and the antineoplastic agent cisplatin. In mammals, damage to the vestibular hair cells is permanent. This study aimed to evaluate the protective effects of nobiletin (NOB) against aminoglycoside-induced hair cell death using utricles collected from adult mice. The utricles removed from CBA/N mice were assigned to eight groups according to the dose of NOB and the administration or not of neomycin. Hair cells in the utricles were counted by double labeling with calmodulin and calbindin. NOB inhibited hair cell death in utricles exposed to neomycin. The protective effect of NOB on hair cells in the utricles was also suggested to have resulted from the inhibition of the production and accumulation of 4-hydroxy-2-nonenal, the final product of lipid peroxide aldehyde. NOB suppressed neomycin-induced hair cell death. The principle of hair cell protection from aminoglycoside-induced hair cell death suggests that NOB inhibits reactive oxygen species formation in the utricles exposed to neomycin.

Objective: The objective was to explore the potential existence and nature of the relationship between serum of uric acid (SUA) and serum uric acid to serum creatinine ratio (SUA/SCr) with reduced estimated glomerular filtration rate (eGFR) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: A cross-sectional study was conducted among apparently healthy subjects with NAFLD (n=485). The association between tertiles of SUA and SUA/SCr with reduced eGFR (n=56) were investigated after adjustments for potentially relevant confounders. Also, the diagnostic performances of SUA and SUA/SCr were evaluated with the receiver operating characteristic (ROC) curve analysis. Results: In the adjusted models, SUA showed a significant positive association with reduced eGFR in the highest tertile (OR 5.65, 95% CI 2.48-12.86, p<0.001), and SUA/SCr, in the lowest tertile (4.21, 95% CI 1.76-10.07, p=0.001). The ROC curve analysis did not reveal any significant difference between the corresponding values of area under the curve for SUA and SUA/SCr (0.70 and 0.67, respectively; p=0.521). Conclusions: We revealed significant and independent associations of elevated SUA and reduced SUA/SCr with kidney function decline in NAFLD. However, the clinical utility of these two biomarkers seemed to be limited for the mentioned purpose and needs further investigations.

Benign paroxysmal positional vertigo (BPPV) is the most common vertigo disease and is more likely to occur in perimenopausal women, suggesting an association with osteoporosis. Since otoconia are primarily composed of calcium carbonate, abnormal calcium metabolism may lead to otoconia dislocation. However, the detailed mechanism is currently unknown. In this study, we investigated the effects of drugs (cadmium and dexamethasone) that cause abnormal calcium metabolism on otolith formation in zebrafish larvae. Here, otolith size was clearly reduced in the cadmium group, and the calcium content of the larvae was also markedly reduced. In contrast, in the dexamethasone group, which also had a lower calcium content than the control group, otolith size increased. Our results suggest that, as in bone, calcium metabolism influences the repeated dissolution and recrystallization of otoliths and maintains homeostasis in response to calcium concentrations in the endolymphatic fluid.

This dissertation aims to explore the adoption of fintech to improve the efficiency, stability, and social impact of microfinance institutions (MFIs) for financial inclusion in Laos. In Chapter 2, we delve into the current state of financial inclusion in Laos and identify the primary barriers and challenges obstructing its progress. Additionally, we analyze the role of MFIs in advancing financial inclusion within the country. In Chapter 3, we examine MFI performance and credit default risk using CAMEL rating systems, allowing us to gain a comprehensive understanding of their financial health when extending loans to underserved populations. The findings highlight the importance of MFIs' risk management and financial stability in advancing greater financial inclusion. Chapter 4 concentrates on the role of fintech, exploring its potential benefits and risks for enhancing the efficiency, stability, and social impact of MFIs in promoting financial inclusion in Laos. This study establishes the groundwork for fostering more inclusive and sustainable financial practices in the country. Furthermore, it emphasizes the necessity of addressing fintech-related risks as well as balancing the relationship and transaction banking to fully maximize its potential for MFIs seeking to enhance their efficiency, stability, and social impact through fintech adoption. To understand the factors that affect fintech adoption in MFIs, we develop a theoretical model in Chapter 5 by extending the Technology Acceptance Model (TAM) with perceived risk, government support, and regulation. Surveying managing directors from MFIs provides useful data, and the effectiveness of the extended TAM is validated through Structured Equation Modeling (SEM). This study contributes to theoretical development by enriching TAM with additional variables. Applied this extended model in the context of MFIs in Laos, it provides a more comprehensive understanding of fintech adoption, strengthening TAM's credibility, and contributing to a robust theoretical framework for fintech adoption within the scope of MFIs. Consequently, our study provides practical guidance for practitioners seeking to strengthen influential factors and overcome obstacles in the fintech adoption of MFIs. Through an examination of the situation of financial inclusion in Laos, the role of MFIs in driving financial inclusion, their performance, credit default risk, and fintech adoption, this dissertation demonstrates the potential of fintech and its role in improving the efficiency, stability, and social impact of MFIs for financial inclusion in Laos. Ultimately, it may contribute to the advancement of the country's financial ecosystem and support societal progress.