ABSTRACT
Patient satisfaction following oculofacial cosmetic procedures depends on preoperative expectations, which may be influenced by online material. Patients with poor health literacy are particularly vulnerable to misinformation and low-quality resources. However, few studies have evaluated the quality of online information on common oculofacial plastic surgeries and procedures. This study aimed to review the literature on the readability and quality of online material related to oculofacial plastic surgery. We conducted a systematic search of the PubMed/MEDLINE database and included 10 studies in our review. Among the readability scores reported in these studies, the lowest was 10, representing a tenth-grade reading level. Furthermore, the online materials were often rated as "poor" quality based on multiple grading scales. Our systematic review of the literature demonstrates that online materials covering common oculofacial plastic surgery procedures are consistently of poor quality and exceed the recommended readability level. Therefore, considering these online materials that influence patient expectations could enable oculofacial plastic surgeons to better tailor their preoperative counseling.
ABSTRACT
Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere's disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials.
Subject(s)
Hearing Loss, Sudden , Labyrinth Diseases , Meniere Disease , Humans , Labyrinth Diseases/drug therapy , Labyrinth Diseases/genetics , Meniere Disease/genetics , Adrenal Cortex Hormones , Steroids/therapeutic useABSTRACT
The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer's and Parkinson's disease (PD), and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with α-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid microRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in PD with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration.
Subject(s)
Discoidin Domain Receptor 1/genetics , Lewy Body Disease/drug therapy , Neurodegenerative Diseases/genetics , Parkinson Disease/drug therapy , alpha-Synuclein/genetics , Alzheimer Disease/complications , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Animals , Discoidin Domain Receptor 1/antagonists & inhibitors , Disease Models, Animal , Humans , Inflammation/complications , Inflammation/drug therapy , Inflammation/genetics , Inflammation/pathology , Lewy Body Disease/genetics , Lewy Body Disease/pathology , Mice , MicroRNAs/genetics , Neurodegenerative Diseases/pathology , Parkinson Disease/complications , Parkinson Disease/genetics , Parkinson Disease/pathology , Pyrimidines/pharmacologyABSTRACT
BACKGROUND AND OBJECTIVES: Inhibition of Abelson (Abl) tyrosine kinase as a therapeutic target has been gaining attention in neurodegeneration. Post-mortem Alzheimer's and Parkinson's disease brains show that the levels of several other tyrosine kinases, including Discoidin Domain Receptors (DDR1/2) are elevated. Knockdown of these tyrosine kinases with shRNA reduces neurotoxic proteins, including alpha-synuclein, beta-amyloid and tau. METHODS: Direct profiling of the pharmacokinetics of multi-kinase inhibitors Nilotinib, Bosutinib, Bafetinib, Radotinib and LCB-03-0110 shows differential levels of brain penetration but the ability of these agents to reduce toxic proteins is independent of brain concentration and selectivity to Abl. RESULTS: Our results indicate that the effective dose of Nilotinib has the lowest plasma:brain ratio (1%) followed by Bosutinib and Radotinib (5%), Bafetinib (12%) and LCB-03-0110 (12%). However, similar doses of multi-kinase Abl/DDR inhibitor Nilotinib, DDR/Src inhibitor LCB-03-0110 and Abl/Src inhibitor Bosutinib were much more effective than the more selective Abl inhibitors Radotinib and Bafetinib. Taken together, these data suggest that a multi-kinase target that includes Abl and other tyrosine kinases (DDRs, and Src) may offer more advantages alleviating neurodegenerative pathologies than the absolute CNS drug concentration and selectivity to Abl. CONCLUSION: DDRs and Src are other potential co-targets with Abl in neurodegeneration.
