20260 research outputs found
Sort by
Single-cell transcriptomics in a child with coenzyme Q10 nephropathy: potential of single-cell RNA sequencing in pediatric kidney disease
No full textBACKGROUND: Coenzyme Q10 (CoQ10) nephropathy is a well-known cause of hereditary steroid-resistant nephrotic syndrome, primarily impacting podocytes. This study aimed to elucidate variations in individual cell-level gene expression in CoQ10 nephropathy using single-cell transcriptomics. METHODS: We conducted single-cell sequencing of a kidney biopsy specimen from a 5-year-old boy diagnosed with a CoQ10 nephropathy caused by a compound heterozygous COQ2 mutation complicated with immune complex-mediated glomerulonephritis. The analysis focused on the proportion of cell types, differentially expressed genes in each cell type, and changes in gene expression related to mitochondrial function and oxidative phosphorylation (OXPHOS). RESULTS: Our findings revealed a uniform downregulation of mitochondrial gene expression across various cell types in the context of these mutations. Notably, there was a specific decrease in mitochondrial gene expression across all cell types. The study also highlighted an altered immune cell population proportion attributed to the COQ2 gene mutation. Pathway analysis indicated a downregulation in OXPHOS and an upregulation of various synthesis pathways, particularly in podocytes. CONCLUSIONS: This study improves our understanding of CoQ10 nephropathy's pathogenesis and highlights the potential applications of single-cell sequencing in pediatric hereditary kidney diseases
Effects of a mobile health coaching intervention on symptom experience, self-management, and quality of life in breast cancer survivors: A quasi-experimental study
No full textBACKGROUND: Patients diagnosed with breast cancer in South Korea have a longer post-diagnosis survival period compared to those in the United States and Europe. Therefore, it is essential to establish an effective posttreatment care system to enhance their quality of life (QOL). This study aimed to evaluate the effectiveness of a mobile health coaching intervention designed to improve symptom experience, self-management, and QOL in patients with breast cancer following the active phase of their treatment. METHODS: This study was a quasi-experimental, pre-post design conducted with breast cancer patients receiving treatment at a tertiary general hospital in Korea from July 2021 to June 2022. Participants were sequentially assigned to the control and intervention groups. Those in the intervention group participated in a 12-week mobile health coaching intervention comprising education sessions, peer support groups, and recording a health diary. The outcome variables were symptom experience, self-management, and QOL. Data were collected at baseline (T0), after the intervention (T1), and 3 months after the intervention (T2) and compared using repeated analysis of variance. RESULTS: Seventy-four participants (mean age 46.93 years) who had completed the active phase of cancer treatment were included. The intervention group showed a significant decrease in symptom experience, from 1.57 +/- 0.46 (T0) to 1.03 +/- 0.46 (T1) (P = .006), and a decrease in psychological symptoms from 1.71 +/- 0.93 (T0) to 1.66 +/- 0.69 (T2) (P = .049). Self-management scores significantly increased from 74.43 +/- 10.72 (T0) to 76.90 +/- 11.99 (T2) (P = .028). QOL improved from 95.83 +/- 18.62 (T0) to 96.40 +/- 15.35 (T2) (P = .015), and emotional well-being increased from 17.42 +/- 4.91 (T0) to 17.50 +/- 3.63 (T2) (P < .001), with all showing significant group x time interactions. CONCLUSIONS: The 12-week mobile health coaching program significantly reduced symptoms, improved self-management, and enhanced overall QOL and emotional well-being in breast cancer survivors who had completed primary treatment. These findings highlight the program's potential to support posttreatment recovery. Further research is needed to assess its long-term effects across diverse patient populations and cancer types to validate its broader effectiveness
Additional Screw Added to the Femoral Neck System Could Enhance the Stability of Pauwel Type III Femoral Neck Fractures: a Finite Element Analysis
No full textBACKGROUD: This study explores effective fixation methods for Pauwel type III femoral neck fractures by evaluating the biomechanical benefits of adding a screw to the Femoral Neck System (FNS). METHODS: Computed tomography (CT) scans of an 82-year-old female patient with an intertrochanteric fracture were used to establish a finite element femur model with heterogeneous material properties. Finite element models of Pauwel type III fractures were created with and without an additional screw. The central and inferior trajectories of the FNS bolt were examined separately and combined with an additional screw for virtual fixation. Walking and stair-climbing loads were applied. RESULTS: With the addition of a screw, both peak maximum and minimum principal strains consistently stayed comparable or decreased in models with both central and inferior bolt trajectories, while the volume of elements with principal strain exceeding 1% decreased by more than half. The peak von Mises stress observed in the implants ranged from 215.7 to 359.3 MPa, remaining below the titanium alloy's yield strength of 800 MPa. For normal walking, the addition of a screw to the central bolt trajectory model decreased the fracture gap by 50.6% and reduced sliding distance by 8.6%. For the inferior bolt trajectory, the gap was reduced by 57.9% and sliding distance by 25.0%. Under stair-climbing conditions, these improvements were also evident; the central trajectory model saw a halved fracture gap and a 7.9% decrease in sliding distance, while the inferior trajectory model experienced a 55.7% gap reduction and a 27.2% decrease in sliding distance. The additional screw increased the area ratio of the fracture site experiencing interfragmentary compression 34%-39%, while the additional screw alleviated peak interfragmentary compression by 12%-18% under both normal walking and stair-climbing conditions. CONCLUSIONS: The addition of a screw reduced the fracture gap, sliding distance, and peak interfragmentary compression, while increasing the area ratio of interfragmentary compression under both walking and stair-climbing loads, regardless of the FNS bolt trajectory, suggesting a better mechanical environment for fracture healing
Erratum: Clinical Feasibility of Vascular Navigation System During Laparoscopic Gastrectomy for Gastric Cancer: A Retrospective Comparison With Propensity-Score Matching
No full textChanges of Clinical Practice Patterns of Allergen Immunotherapy in Korea
No full textThis study aimed to identify recent changes of AIT treatment behaviors in real-world clinical practice using a questionnaire survey in Korea. The questionnaire on AIT prescriptions and practical experiences was distributed to all members of the Korean Academy of Asthma Allergy and Clinical Immunology in June 2022. The responses were analyzed and compared with the results from 2009 and 2017. In total, 115 responses (10.1%) were collected; 58 (50.4%) from internal medicine, 34 (29.6%) from pediatricians, and 21 (18.3%) from otolaryngologists. The prescription rate for subcutaneous immunotherapy (SCIT) was 53.8%, showing a decrease from those in 2009 and 2017; however, that for sublingual immunotherapy (SLIT) increased steadily, reaching 17.9% in 2009, 40.3% in 2017, and 46.2% in 2022. The prescription rates for asthma and atopic dermatitis increased by 4.6% and 7.9%, respectively. The most frequently prescribed allergens for SCIT in 2022 were house dust mites (32.9%), pollen (30.6%), and animal dander (28.2%), with the rate for animal dander showing a significant increase from 10.3% in 2009. Most physicians (93%) used mixed allergens for SCIT, with 42.8% using a combination of 5 or more allergens. Fifty-eight (67.4%) respondents reported cases of anaphylaxis during SCIT and 36.2% reported systemic adverse reactions during SLIT. In conclusion, SLIT prescriptions, AIT for asthma and atopic dermatitis, and AIT with animal dander increased significantly from 2009 to 2022. Serial surveys of AIT practices are helpful in identifying the changes of real-world clinical practice of AIT
Comment on “Lower incidence of hepatocellular carcinoma with tenofovir alafenamide in chronic hepatitis B: Evidence from a large-scale cohort”
No full textC/EBPα activates Irf8 expression in myeloid progenitors at the +56-kb enhancer to initiate cDC1 development
No full textDevelopment of type 1 conventional dendritic cells (cDC1s) underlies the capacity to generate antiviral and antitumor immune responses. Here, we identify the basis for cDC1 development from its earliest progenitors, determining the hierarchy of several required transcription factors and uncovering a series of mandatory cis interactions between constituent enhancers within the Irf8 superenhancer. We produced in vivo mutations of two C/EBPalpha binding sites that comprise the Irf8 +56-kilobase (kb) enhancer that markedly reduced IRF8 expression in all myeloid progenitors and impaired cDC1 development. These sites did not bind RUNX1 or RUNX3, and C/EBPalpha expression was instead regulated by their action at the Cebpa +37-kb enhancer, placing RUNX factors upstream of Cebpa in regulating Irf8. Last, we demonstrate that cis interactions between the +56-kb Irf8 enhancer and the previously reported +41- and +32-kb Irf8 enhancers are mandatory in the sequential progression of these stage-specific constituent elements
TRIM22 functions as a scaffold protein for autophagy initiation
No full textTripartite motif (TRIM) family proteins are increasingly recognized as important regulators of autophagy under various physiological and pathological conditions. TRIM22 has been previously shown to mediate autophagosome-lysosome fusion, but its potential role in earlier stages of autophagy remained unexplored. In this study, we investigated the function of TRIM22 in autophagy initiation. Overexpression of TRIM22 increased LC3-II levels and enhanced autophagic flux without affecting mTOR and AMPK activity. We found that TRIM22 interacts with components of both the ULK1 complex and the class III PI3K complex through distinct domains, recruiting them into punctate structures that represent autophagosome formation sites. Domain mapping revealed that the SPRY domain mediates interactions with ATG13 and FIP200, while the N-terminal region interacts with ULK1 and ATG101. The B-box domain of TRIM22 was identified as crucial for its interaction with Beclin-1, a key component of the class III PI3K complex. Deletion of this domain impaired the ability of TRIM22 to assemble the class III PI3K complex and induce autophagic flux. Interestingly, competitive binding assays revealed that Beclin-1 and PLEKHM1 bind to the same region of TRIM22, suggesting a mechanism for coordinating different stages of autophagy. The Alzheimer's disease-associated TRIM22 variant R321K maintained autophagy initiation function in both cell lines and primary neurons. These findings demonstrate that TRIM22 acts as a scaffold protein to promote autophagy initiation, in addition to its previously described role in autophagosome-lysosome fusion. Our study provides new insights into the molecular mechanisms by which TRIM proteins regulate multiple stages of the autophagy process
Empagliflozin Alleviates Hepatic Steatosis and Oxidative Stress via the NRF1 Pathway in High-Fat Diet-Induced Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease
No full textEmpagliflozin (EMPA)-a sodium-glucose cotransporter type 2 inhibitor-reduces endoplasmic reticulum (ER) stress, oxidative stress, and inflammation during metabolic dysfunction-associated steatotic liver disease (MASLD) progression. However, the direct effects of EMPA on hepatic lipid metabolism and oxidative stress are unclear. Through the current study, we seek to explore the effects of EMPA on oxidative stress and related mechanisms in MASLD. To this end, MASLD was induced in C57BL/6J mice using a high-fat diet (HFD); nuclear respiratory factor 1 (NRF1) was downregulated via viral transduction (AAV8-shNrf1). Glucose homeostasis and liver histology were assessed, and oxidative stress and inflammation were measured. HFD-fed mice-derived liver tissue samples exhibited more lipid droplets, higher triglyceride levels, and elevated oxidative and ER stress than chow diet (CD)-fed mice. EMPA attenuated HFD-induced liver oxidative and ER stress. Additionally, the HFD significantly decreased NRF1 and Sirtuin (SIRT)7 expression compared with CD, which was rescued by EMPA treatment. However, these results did not affect insulin resistance or lipid synthesis-related changes upon EMPA treatment in the Nrf1-knockdown mice. Furthermore, EMPA alleviated HFD-induced hepatic steatosis and oxidative stress; however, these effects were lost in Nrf1-knockdown mice. Collectively, the results of this study suggest that EMPA ameliorates MASLD by reducing steatosis and attenuating oxidative stress via NRF1
Impact of the COVID-19 pandemic on the clinical performance of medical students: a retrospective study in Korea
No full textPURPOSE: The COVID-19 (coronavirus disease 2019) pandemic led to significant changes in clinical clerkships, including reduced ward rounds. We aimed to determine how the pandemic-induced changes in the clinical practice environment affect the clinical performance of medical students. METHODS: We analyzed objective structured clinical examination scores of third- and fourth-year medical students from 2019-2020 and 2020-2021 across six stations by the Seoul-Gyeonggi Consortium. Clinical, communication, and ability scores were measured and analyzed using repeated-measures multivariate analysis of variance. RESULTS: The interaction between clinical practice progress and pandemic-induced changes significantly affected physical examination and medical history scores, though the differences were not substantial. Patient-physician interaction significance varied by measurement period. Clinical communication ability also showed significant differences based on the measurement period and practical experience. CONCLUSION: During the pandemic, alternative learning methods, including self-learning, simulation/practice, and peer role-play, helped improve medical competency in areas such as history-taking and physical examination. However, these were less effective in improving patient-physician interactions or clinical communication efficacy. Alternative learning methods have limitations, and they cannot replace direct patient encounters in clinical practice