P1: Assessment of Metabolism-Induced Hepatotoxicity on a 384-Pillar Plate

Microarray bioprinting technology has been explored to create miniaturized 3D cell cultures on a 384-pillar plate, which were combined with drug metabolizing enzymes (DMEs) and test compounds in a 384-well plate for metabolism-induced toxicity assays. Our goal in this study was to demonstrate rapid assessment of metabolism- induced toxicity on the 384-pillar plate and obtain reliable and highly predictive information on compound\u27s hepatotoxicity in vivo. Briefly, human cells including Hep3B human hepatoma cell line as well as human embryonic kidney 293 (HEK 293) cell were encapsulated in alginate-Matrigel on the 384-pillar plate. Test compounds and six different DMEs including cytochromes P450 (CYP450) and UDP-glucuronosyltransferase (UGT) were dispensed in the 384-well plate. By sandwiching the 384-pillar plate onto the 384-well plate, human cells were exposed to the compounds and their metabolites generated by DMEs. The cells were stained with luminescent and fluorescent dyes and IC50 values were calculated using the luminescence and fluorescence obtained. In summary, our approach allowed us to assess mechanisms of metabolism-induced toxicity in high throughput. Thus, the 384- pillar plate could be used as a high-throughput, early stage, microscale alternative to conventional in vitro multi-well plate platforms and provide a rapid and inexpensive assessment of metabolism-induced toxicity at early phases of drug development.https://engagedscholarship.csuohio.edu/u_poster_2017/1053/thumbnail.jp

A scoping review of music-based interventions for swallowing difficulties: implications for treating older adults with presbyphagia

ObjectivesPresbyphagia refers to age-related changes in the swallowing mechanism (e.g., reduced skeletal muscle strength that decreases bolus control). If left untreated, these changes can lead to dysphagia, which refers to impaired swallowing (e.g., coughing or choking when eating). Given that swallowing difficulties are common among older adults that they make up the fastest growing age group globally, the need for interventions to address presbyphagia is gaining urgency. To begin to address this need, we conducted a scoping review to analyze music therapy research aimed at enhancing swallowing function. The objective was to identify key intervention characteristics and propose clinical implications for treating presbyphagia using music therapy.MethodsThis review followed the methodological frameworks outlined by Arksey and O’Malley and Levac et al. and used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews for analysis and reporting. Four electronic databases (i.e., ProQuest, PubMed, RISS, Web of Science) were searched for quantitative and qualitative studies in English or Korean that used music-based interventions to address swallowing function in older adults. Content analysis was conducted to identify and compare the main features of music interventions for swallowing difficulties among older adults.ResultsTen articles were identified and analyzed. It was found that three core components–respiration, vocalization, and singing–were employed to enhance swallowing function in populations with neurological impairments, dementia, or head and neck cancer. Notably, actions closely linked to swallowing function, such as laryngeal elevation and oral movements, were utilized therapeutically to speak or sing. Based on these characteristics, clinical implications are proposed to address presbyphagia.ConclusionSinging entails a systematic and focused incorporation of stepwise activities that can be used to address swallowing disorders. In this context, critical clinical implications that music therapists should consider when treating individuals with presbyphagia include warmup breathing, vocalizing targeting laryngeal control, and singing targeting oral motor control. This review can contribute to the expansion of music therapy with older adults and the advancement of music therapy techniques

In vivo and in vitro studies of Mgs1 suggest a link between genome instability and Okazaki fragment processing

The non-essential MGS1 gene of Saccharomyces cerevisiae is highly conserved in eukaryotes and encodes an enzyme containing both DNA-dependent ATPase and DNA annealing activities. MGS1 appears to function in post-replicational repair processes that contribute to genome stability. In this study, we identified MGS1 as a multicopy suppressor of the temperature-sensitive dna2Δ405N mutation, a DNA2 allele lacking the N-terminal 405 amino acid residues. Mgs1 stimulates the structure-specific nuclease activity of Rad27 (yeast Fen1 or yFen1) in an ATP-dependent manner. ATP binding but not hydrolysis was sufficient for the stimulatory effect of Mgs1, since non-hydrolyzable ATP analogs are as effective as ATP. Suppression of the temperature-sensitive growth defect of dna2Δ405N required the presence of a functional copy of RAD27, indicating that Mgs1 suppressed the dna2Δ405N mutation by increasing the activity of yFen1 (Rad27) in vivo. Our results provide in vivo and in vitro evidence that Mgs1 is involved in Okazaki fragment processing by modulating Fen1 activity. The data presented raise the possibility that the absence of MGS1 may impair the processing of Okazaki fragments, leading to genomic instability

Myxoid Solitary Fibrous Tumor of the Retroperitoneum: MRI Findings with the Pathologic Correlation

We report here on a case of solitary fibrous tumor of the retroperitoneum, and the tumor displayed a predominantly myxoid histology. A 56-year-old man presented with an incidentally detected retroperitoneal mass. On the MR images, the mass was observed as having iso-signal intensity on the T1-weighted images and high signal intensity on the fat-saturated T2-weighted images. The mass showed intense enhancement on the Gd-DTPA enhanced T1-weighted images. At surgery, a well-defined solid mass was found in the left retroperitoneum. The histological diagnosis was made as solitary fibrous tumor with a predominantly myxoid histology

Titanium Oxide Nanotube Surface Topography and MicroRNA-488 Contribute to Modulating Osteogenesis

Understanding the biocomplexity of cell behavior in relation to the topographical characteristics of implants is essential for successful osseointegration with good longevity and minimum failure. Here, we investigated whether culture on titanium oxide (TiO2) nanotubes of various diameters could affect the behavior and differentiation of MC3T3-E1 cells. Among the tested nanotubes, those of 50 nm in diameter were found to trigger the expression of the osteoblast-specific transcription factors, sp7 and Dlx5, and upregulate the expression of alkaline phosphatase (ALP). Here, we report that miR-488 was significantly induced in osteoblasts cultured on 50 nm nanotubes and continued to increase with the progression of osteoblast differentiation. Furthermore, downregulation of miR-488 suppressed the expression levels of ALP and matrix metalloprotease-2 (MMP-2). This suppression of ALP transcription was overcome by treatment with the MMP-2 activator, bafilomycin A1. Collectively, these results suggest that 50 nm is the optimum TiO2 nanotube diameter for implants, and that modulation of miR-488 can change the differentiation activity of cells on TiO2 nanotubes. This emphasizes that we must fully understand the physicochemical properties of TiO2 nanotubes and the endogenous biomolecules that interact with such surfaces, in order to fully support their clinical application

Primary Calcified T-Cell Lymphoma of the Urinary Bladder: A Case Report

Primary malignant lymphoma of the urinary bladder is extremely rare, and to our knowledge, no case described in the radiologic literature has been accompanied by calcification. We report a case in which the condition was associated with calcification, and describe the pelvic CT and MR imaging findings