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

Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin

AbstractMurine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2Å and 2.5Å resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase

Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation

Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity. Accordingly, negative regulation of the DDR is as critical as its activation. In this study, we have identified ring finger protein 126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing 53BP1. RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but also of RNF168, FK2, RAP80, and BRCA1. However, the iRIF formation of H2AX, MDC1, and RNF8 is maintained, indicating that RNF126 acts between RNF8 and RNF168 during the DDR. In addition, RNF126 overexpression consistently results in the loss of RNF168-mediated H2A monoubiquitination at lysine 13/15 and inhibition of the non-homologous end joining capability. Taken together, our findings reveal that RNF126 is a novel factor involved in the negative regulation of DDR, which is important for sustaining genomic integrity

Use of Aripiprazole in Clozapine Induced Enuresis: Report of Two Cases

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately

Suppression of lung cancer progression by biocompatible glycerol triacrylate–spermine-mediated delivery of shAkt1

Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy. Methods: The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance. Results: The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively. Conclusion: Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy

Artificial intelligence for the detection of sacroiliitis on magnetic resonance imaging in patients with axial spondyloarthritis

BackgroundMagnetic resonance imaging (MRI) is important for the early detection of axial spondyloarthritis (axSpA). We developed an artificial intelligence (AI) model for detecting sacroiliitis in patients with axSpA using MRI.MethodsThis study included MRI examinations of patients who underwent semi-coronal MRI scans of the sacroiliac joints owing to chronic back pain with short tau inversion recovery (STIR) sequences between January 2010 and December 2021. Sacroiliitis was defined as a positive MRI finding according to the ASAS classification criteria for axSpA. We developed a two-stage framework. First, the Faster R-CNN network extracted regions of interest (ROIs) to localize the sacroiliac joints. Maximum intensity projection (MIP) of three consecutive slices was used to mimic the reading of two adjacent slices. Second, the VGG-19 network determined the presence of sacroiliitis in localized ROIs. We augmented the positive dataset six-fold. The sacroiliitis classification performance was measured using the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The prediction models were evaluated using three-round three-fold cross-validation.ResultsA total of 296 participants with 4,746 MRI slices were included in the study. Sacroiliitis was identified in 864 MRI slices of 119 participants. The mean sensitivity, specificity, and AUROC for the detection of sacroiliitis were 0.725 (95% CI, 0.705–0.745), 0.936 (95% CI, 0.924–0.947), and 0.830 (95%CI, 0.792–0.868), respectively, at the image level and 0.947 (95% CI, 0.912–0.982), 0.691 (95% CI, 0.603–0.779), and 0.816 (95% CI, 0.776–0.856), respectively, at the patient level. In the original model, without using MIP and dataset augmentation, the mean sensitivity, specificity, and AUROC were 0.517 (95% CI, 0.493–0.780), 0.944 (95% CI, 0.933–0.955), and 0.731 (95% CI, 0.681–0.780), respectively, at the image level and 0.806 (95% CI, 0.729–0.883), 0.617 (95% CI, 0.523–0.711), and 0.711 (95% CI, 0.660–0.763), respectively, at the patient level. The performance was improved by MIP techniques and data augmentation.ConclusionAn AI model was developed for the detection of sacroiliitis using MRI, compatible with the ASAS criteria for axSpA, with the potential to aid MRI application in a wider clinical setting