Navigating the Experience of Burnout of Immigrant Music Therapists in the United States

This study explored the experiences of burnout of immigrant music therapists who currently live and work in the United States. The purpose of this study was to examine how immigrant music therapists’ cultural adjustment may influence their experience with burnout and to guide participants articulate their burnout experiences through the use of musical improvisation as a method. Qualitative phenomenological inquiry and Arts-Based Research as a method were used in this study. Musical improvisation and open-ended interviews were conducted with three female participants possessing various years of clinical experience. Music as well as interviews were transcribed and analyzed for themes. Three essential categories emerged: (1) participants’ burnout experiences, (2) themes across immigrant music therapists’ experiences, and (3) characteristics of burnout. Each participant’s experience in musical improvisation was narrated based on the researcher’s reaction, an external music therapist’s reaction, and the participant’s reaction to improvised music. The two themes that emerged across immigrant music therapists’ experiences were communication styles and cultural clashes. Within the category of characteristics of burnout, the following four themes emerged: (1) isolation, (2) frustration, (3) fatigue, and (4) job dissatisfaction. The study indicated that immigrant music therapists’ experience of burnout may not always be caused by acculturative stress, when an individual has developed coping strategies. The qualities of the participants’ emotional expressions through musical medium pertaining to their past burnout moments differed based on an individual’s phase of cultural adjustment. Implications for immigrant music therapists and music therapy educators are discussed

Metabolic Network Modeling to Unravel the Impact of Copper Deficiency and High-fat Diet on Liver Metabolism

Fatty liver disease is a common health problem caused by an imbalance in the intake, utilization, and distribution of energy. High-fat and high-carbohydrate diets have been identified as major risk factors for fatty liver disease. Other contributors and modifiers can also influence the development of liver damage. Intriguingly, inappropriate copper (Cu) levels in the diet and organs are associated with fatty liver disease, though the exact way in which Cu deficiency or toxicity contributes to metabolic issues is not yet clear. Cu is necessary for several biological processes, including energy production and redox balance. Further research should be taken to determine exactly how Cu deficiency and toxicity cause metabolic complications. To fill in this knowledge gap, this research aimed to use human genome-scale metabolic modeling with incorporating transcriptomic data and determine how Cu deficiency and high-fat diet affect metabolism in the liver. Results revealed that high-fat diet combining with Cu deficiency induces dramatic effects on fatty acid catabolism, energy metabolism, and NADPH balance, which is consistent with gene expression changes. In addition, the model proposed new findings in reduced ascorbate recycling, oxalate synthesis, and betaine synthesis which can affect other minerals or organs. These results presented Cu limitation-induced exacerbation of fatty liver disease and propose underlying mechanisms. Advisors: Hyun-Seob Song and Jaekwon Le

Contribution of actin filaments and microtubules to cell elongation and alignment depends on the grating depth of microgratings

Additional file 1: Figure S1. (A) A phase contrast image of TCPS surface. Bar, 100 μm. (B) An imageshowing FN-lines (1 μm line and spacing) obtained by Atomic Force Microscopy (AFM) (Dimension 3100with a Nanoscope III controller, Digital Instruments) using silicon cantilevers (spring constant; 50 Nm-1)(RTESP, Veeco Probes) in contact mode. (C-E) SEM (Scanning electron microscopy) (6010 LV, JEOL)images showing the cross section of three different microgratings; 1 μm gratings with 0.35 um depth (C) and1 μm depth (D) and 2 μm gratings with 2 μm depth (E). Figure S2. (A) Fluorescence image of a RPE-1 cell stably expressing GFP/centrin cell on 1 μm gratings (1 μm deep). Bar, 30 μm. A yellow arrow indicates the direction of cell elongation. (B) Average cell aspect ratio (R) of cells on 1 μm gratings (0.35 or 1 μm deep) and 2 μm gratings with/without CD treatment. n: number of cells. ***P < 0.001. Data were analyzed using one-way ANOVA and a Bonferroni post hoc test. Error bar denotes the standard deviation of the mean. Figure S3. Alignment of actin and vinculin to the different substrates (Flat TCPS surface, FN-lines, and 1 μm gratings (0.35 or 1μm deep)). The alignment angle was measured as an angle difference of actin or vinculin orientation to the long axis of a cell on flat PDMS surface or the long axis of the FN-line or each micrograting. #: the number of cells. Error bar denotes the standard deviation of the mean. Figure S4. Merged image of MTs (Green fluorescence) and pattern (phase contrast) of cells on 1 μm grating (1 μm deep) in the presenceof CD at 1 μM

Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome

Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined the relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and risk of AD. HSD17B1 encodes the enzyme 17β-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol. Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31–78 years of age, were followed at 14–18-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the HSD17B1 gene region, and their association with incident AD was examined. Results. Age at onset was earlier, and risk of AD was elevated from two- to threefold among women homozygous for the minor allele at 3 SNPs in intron 4 (rs676387), exon 6 (rs605059), and exon 4 in COASY (rs598126). Carriers of the haplotype TCC, based on the risk alleles for these three SNPs, had an almost twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1–3.1). Conclusion. These findings support experimental and clinical studies of the neuroprotective role of estrogen

Particulate matter 10 exposure affects intestinal functionality in both inflamed 2D intestinal epithelial cell and 3D intestinal organoid models

BackgroundA growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease.ObjectiveThe purpose of this study was to dissect the pathology mechanism of PM10 exposure in inflamed intestines.MethodsIn this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic in vivo cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like in vitro models.ResultsInflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine.ConclusionsAccording to our findings, 2D hIEC and 3D hIO models could be powerful in vitro platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions

Role of NFAT5 in the Immune System and Pathogenesis of Autoimmune Diseases

The nuclear factor of activated T cells (NFAT5), also known as a tonicity-responsive enhancer-binding protein, was originally identified as a key transcription factor involved in maintaining cellular homeostasis against hypertonic and hyperosmotic environments. Although NFAT5 has been expressed and studied in various types of hyperosmolar tissues, evidence has emerged that NFAT5 plays a role in the development and activation of immune cells, especially T cells and macrophages. The immune-regulatory function of NFAT5 is achieved by inducing different target genes and different signaling pathways in both tonicity-dependent and -independent manners. Particularly in response to hyperosmotic stress, NFAT5 induces the generation of pathogenic TH17 cells and pro-inflammatory macrophages, contributing to autoimmune and inflammatory diseases. Meanwhile, with tonicity-independent stimuli, including activation of the Toll-like receptors and inflammatory cytokines, NFAT5 also can be activated and promotes immune cell survival, proliferation, migration, and angiogenesis. Moreover, under isotonic conditions, NFAT5 has been implicated in the pathogenesis of a variety of inflammatory and autoimmune diseases including rheumatoid arthritis. This review describes the current knowledge of NFAT5, focusing on its immune-regulatory functions, and it highlights the importance of NFAT5 as a novel therapeutic target for chronic inflammatory diseases

Clinical outcomes in pediatric patients with normal renal histopathology

Background There have been some cases where abnormal histopathologic findings could not be found in the kidney could even with proper specimen collection through percutaneous renal biopsy (PRB) in accordance with its indication. We analyzed the incidence and clinical outcomes of children who showed normal histopathological findings in their PRBs. Methods The medical records of 552 pediatric subjects who underwent PRB between 2005 and 2016 were reviewed. Twenty-six subjects were excluded because allograft biopsy was performed in nine subjects, and the age at biopsy was greater than 18 years in 17 subjects. Finally, 526 subjects were enrolled in this study. Results Of the 526 pediatric patients, 32 (6.1%) showed no histopathological abnormalities in their PRBs. The male-to-female ratio of the patients was 1.9:1, and the mean ages at the first visit and at biopsy were 10.6 ± 4.1 and 11.4 ± 3.8 years, respectively. In accordance with the biopsy indications, recurrent gross hematuria showed the highest incidence rate, but combined hematuria and proteinuria had the lowest incidence rate regarding normal renal histopathology among all the subjects. At a mean follow-up of 35.5 ± 23.6 months, urinary abnormalities had improved in more than 50% of the subjects with normal renal histopathology, and none of the patients showed progression to end-stage renal disease or required rebiopsy due to symptom worsening during the follow-up period. Conclusion The clinical outcomes of children with normal PRB histopathologic findings are generally good. Further studies to evaluate their long-term outcomes are needed

Gene-Wise Association of Variants in Four Lysosomal Storage Disorder Genes in Neuropathologically Confirmed Lewy Body Disease

Objective Variants in GBA are associated with Lewy Body (LB) pathology. We investigated whether variants in other lysosomal storage disorder (LSD) genes also contribute to disease pathogenesis. Methods We performed a genetic analysis of four LSD genes including GBA, HEXA, SMPD1, and MCOLN1 in 231 brain autopsies. Brain autopsies included neuropathologically defined LBD without Alzheimer Disease (AD) changes (n = 59), AD without significant LB pathology (n = 71), Alzheimer disease and lewy body variant (ADLBV) (n = 68), and control brains without LB or AD neuropathology (n = 33). Sequencing of HEXA, SMPD1, MCOLN1 and GBA followed by ‘gene wise’ genetic association analysis was performed. To determine the functional effect, a biochemical analysis of GBA in a subset of brains was also performed. GCase activity was measured in a subset of brain samples (n = 64) that included LBD brains, with or without GBA mutations, and control brains. A lipidomic analysis was also performed in brain autopsies (n = 67) which included LBD (n = 34), ADLBV (n = 3), AD (n = 4), PD (n = 9) and control brains (n = 17), comparing GBA mutation carriers to non-carriers. Results In a ‘gene-wise’ analysis, variants in GBA, SMPD1 and MCOLN1 were significantly associated with LB pathology (p range: 0.03–4.14 x10-5). Overall, the mean levels of GCase activity were significantly lower in GBA mutation carriers compared to non-carriers (p<0.001). A significant increase and accumulation of several species for the lipid classes, ceramides and sphingolipids, was observed in LBD brains carrying GBA mutations compared to controls (p range: p<0.05-p<0.01). Interpretation Our study indicates that variants in GBA, SMPD1 and MCOLN1 are associated with LB pathology. Biochemical data comparing GBA mutation carrier to non-carriers support these findings, which have important implications for biomarker development and therapeutic strategies

Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated GNB2L1 and CAV1 expression were enriched in the EGFR TKI-resistant group. Moreover, GZMK upregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC