Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Evaluating the HYDRASHIFT 2/4 Daratumumab assay: a powerful approach to assess treatment response in multiple myeloma.

OBJECTIVES: This study evaluates the HYDRASHIFT assay's effectiveness in mitigating daratumumab interference on serum protein tests during multiple myeloma (MM) treatment, aiming to ensure an accurate assessment of treatment response. METHODS: We analyzed 113 serum samples from 68 MM patients undergoing daratumumab treatment, employing both standard IF and the HYDRASHIFT assay. The assay's precision was determined through intra-day and inter-day variability assessments, while its specificity was verified using serum samples devoid of daratumumab. Comparative analysis of IF results, before and after the application of the HYDRASHIFT assay, facilitated the categorization of treatment responses in alignment with the International Myeloma Working Group's response criteria. RESULTS: The precision underscored the assay's consistent repeatability and reproducibility, successfully eliminating interference of daratumumab-induced Gκ bands. Specificity assessments demonstrated the assay's capability to distinguish daratumumab from both isatuximab and naturally occurring M-proteins. Of the analyzed cases, 91 exhibited successful migration of daratumumab-induced Gκ bands, thereby enhancing the accuracy of treatment response classification. The remaining 22 cases did not show a visible migration complex, likely due to the low concentration of daratumumab in the serum. These findings underscore the assay's critical role in distinguishing daratumumab from endogenous M-protein, particularly in samples with a single Gκ band on standard IF, where daratumumab and endogenous M-protein had co-migrated. CONCLUSIONS: The HYDRASHIFT assay demonstrates high precision, specificity, and utility in the accurate monitoring of treatment responses in MM patients receiving daratumumab. This assay represents a significant advancement in overcoming the diagnostic challenges posed by daratumumab interference.

Assessing the Fear Factor of Coronavirus Disease 2019 (COVID-19) in Korea Using the COVID-19 Phobia Scale: A Cross-Sectional Study.

BACKGROUND: A study on coronavirus disease 2019 (COVID-19) phobia among students revealed that fear of contracting COVID-19 was associated with commuting to school and spending time with others at school. Therefore, it is the need-of-the-hour for the Korean government to identify factors affecting COVID-19 phobia among university students and to consider these factors while framing the policy direction for the process of returning to normalcy in university education. Consequently, we aimed to identify the current state of COVID-19 phobia among Korean undergraduate and graduate students and the factors affecting COVID-19 phobia. METHODS: This cross-sectional survey was conducted to identify the factors affecting COVID-19 phobia among Korean undergraduate and graduate students. The survey collected 460 responses from April 5 to April 16, 2022. The questionnaire was developed based on the COVID-19 Phobia Scale (C19P-S). Multiple linear regression was performed on the C19P-S scores using five models with the following dependent variables: Model 1, total C19P-S score; Model 2, psychological subscale score; Model 3, psychosomatic subscale score; Model 4, social subscale score; and Model 5, economic subscale score. The fit of these five models was established, and a P-value of less than 0.05 (F test) was considered statistically significant. RESULTS: An analysis of the factors affecting the total C19P-S score led to the following findings: women significantly outscored men (difference: 4.826 points, P = 0.003); the group that favored the government's COVID-19 mitigation policy scored significantly lower than those who did not favor it (difference: 3.161 points, P = 0.037); the group that avoided crowded places scored significantly higher than the group that did not avoid crowded places (difference: 7.200 points, P < 0.001); and those living with family/friends scored significantly higher than those in other living situations (difference: 4.606 points, P = 0.021). Those in favor of the COVID-19 mitigation policy had significantly lower psychological fear than those who were against it (difference: -1.686 points, P = 0.004). Psychological fear was also significantly higher for those who avoided crowded places compared to those who did not difference: 2.641 points, P < 0.001). Fear was significantly higher in people cohabitating than those living alone (difference: 1.543 points, P = 0.043). CONCLUSION: The Korean government, in their pursuit of a policy that eases COVID-19-related restrictions, will also have to spare no efforts in providing correct information to prevent the escalation of COVID-19 phobia among people with a high fear of contracting the disease. This should be done through trustworthy information sources, such as the media, public agencies, and COVID-19 professionals.

Analysis of MicroRNA Signature Differentially Expressed in Pancreatic Islet Cells Treated with Pancreatic Cancer-Derived Exosomes.

Since the majority of patients with pancreatic cancer (PC) develop insulin resistance and/or diabetes mellitus (DM) prior to PC diagnosis, PC-induced diabetes mellitus (PC-DM) has been a focus for a potential platform for PC detection. In previous studies, the PC-derived exosomes were shown to contain the mediators of PC-DM. In the present study, the response of normal pancreatic islet cells to the PC-derived exosomes was investigated to determine the potential biomarkers for PC-DM, and consequently, for PC. Specifically, changes in microRNA (miRNA) expression were evaluated. The miRNA specimens were prepared from the untreated islet cells as well as the islet cells treated with the PC-derived exosomes (from 50 patients) and the healthy-derived exosomes (from 50 individuals). The specimens were subjected to next-generation sequencing and bioinformatic analysis to determine the differentially expressed miRNAs (DEmiRNAs) only in the specimens treated with the PC-derived exosomes. Consequently, 24 candidate miRNA markers, including IRS1-modulating miRNAs such as hsa-miR-144-5p, hsa-miR-3148, and hsa-miR-3133, were proposed. The proposed miRNAs showed relevance to DM and/or insulin resistance in a literature review and pathway analysis, indicating a potential association with PC-DM. Due to the novel approach used in this study, additional evidence from future studies could corroborate the value of the miRNA markers discovered.

A novel splicing variant in GALNS in mucopolysaccharidosis IVA and the necessity of re-evaluating primer sequences.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the GALNS gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA. A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A > T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G > A (p.(Gly340Asp)) and c.566+3A > T (p.(?)), in the GALNS gene. On mRNA sequencing, c.566+3A > T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G > A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G > C) at the primer annealing location. We present a novel intronic variant with a splicing defect in the GALNS gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS.

Correlation between peripheral blood automated hematopoietic progenitor cell counts and flow cytometric CD34+ cell counts differs according to diagnosis in patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND: An automated hematopoietic progenitor cell count measurement in Sysmex XN analyzer (XN-HPC) has been developed to assist flow cytometry CD34+ cell count measurement, which requires technical expertise and a long turnaround time. Here, we evaluated the correlation between XN-HPC count and flow cytometric CD34+ cell count in pre-harvest peripheral blood (PB) samples from patients undergoing autologous peripheral blood stem cell (PBSC) transplantation according to diagnosis and investigated the possible cause of the decreased correlation in plasma cell neoplasm patients. MATERIALS AND METHODS: We retrospectively included 399 patient data that had matched PB XN-HPC count and CD34+ cell count of PB and apheresis product from Samsung Medical Center (SMC) and the Hematopoietic Stem Cell (HSC) registry. We assessed the diagnostic accuracy and the potential cutoff values of XN-HPC count for predicting adequate PBSC collection. RESULTS: The PB XN-HPC count was 1.6 and 1.3-fold higher than the CD34+ cell count in SMC (25.0 vs 15.9/µl) and the HSC registry (20.0 vs 15.2/µl), respectively. Overall the correlation between the PB XN-HPC and CD34+ cell count was moderate (SMC, r = 0.71; HSC registry, r = 0.66). A significant proportional and systemic bias with overestimation of XN-HPC count were noted in the plasma cell neoplasm patients in both SMC and the HSC registry. However, no significant difference in correlation was observed according to myeloma-related laboratory parameters in plasma cell neoplasm patients. CONCLUSION: Our results suggest that XN-HPC count should be interpreted cautiously in cancer patients undergoing autologous PBSC transplantation, especially in those with plasma cell neoplasm.

Efficient Generation of Dopamine Neurons by Synthetic Transcription Factor mRNAs.

Generation of functional dopamine (DA) neurons is an essential step for the development of effective cell therapy for Parkinson's disease (PD). The generation of DA neurons can be accomplished by overexpression of DA-inducible genes using virus- or DNA-based gene delivery methods. However, these gene delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene delivery avoids this problem and therefore is considered safe to use in the development of cell-based therapy. Thus, we used mRNA-based gene delivery method to generate safe DA neurons. In this study, we generated transformation-free DA neurons by transfection of mRNA encoding DA-inducible genes Nurr1 and FoxA2. The delivery of mRNA encoding dopaminergic fate inducing genes proved sufficient to induce naive rat forebrain precursor cells to differentiate into neurons exhibiting the biochemical, electrophysiological, and functional properties of DA neurons in vitro. Additionally, the generation efficiency of DA neurons was improved by the addition of small molecules, db-cAMP, and the adjustment of transfection timing. The successful generation of DA neurons using an mRNA-based method offers the possibility of developing clinical-grade cell sources for neuronal cell replacement treatment for PD.

LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson's disease model.

The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNA-binding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson's disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells.

Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage.

Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.

Bulk micromachining of Si by metal-assisted chemical etching.

Bulk micromachining of Si is demonstrated by the well-known metal-assisted chemical etching (MaCE). Si microstructures, having lateral dimension from 5 µm up to millimeters, are successfully sculpted deeply into Si substrate, as deep as >100 µm. The key ingredient of this success is found to be the optimizations of catalyst metal type and its morphology. Combining the respective advantages of Ag and Au in the MaCE as a Ag/Au bilayer configuration leads to quite stable etch reaction upon a prolonged etch duration up to >5 h. Further, the permeable nature of the optimized Ag/Au bilayer metal catalyst enables the etching of pattern features having very large lateral dimension. Problems such as the generation of micro/nanostructures and chemical attacks on the top of pattern surface are successfully overcome by process optimizations such as post-partum sonication treatment and etchant formulation control. The method can also be successful to vertical micromachining of Si substrate having other crystal orientations than Si(100), such as Si(110) and Si(111). The simple, easy, and low-cost nature of present approach may be a great help in bulk micromachining of Si for various applications such as microelectromechanical system (MEMS), micro total analysis system (µTAS), and so forth.

Quality of Care in Hospitals and the Use of Mobile-Based Personal Health Record Applications: An Exploratory Study Using National Hospital Evaluation Data.

The use of mobile-based personal health record (m-PHR) applications at the hospital level has been minimally studied. This study aimed to investigate the relationship between m-PHR use and quality of care. A cross-sectional study design was employed, analyzing data from 99 hospitals. Two data sources were utilized: a previous m-PHR investigation conducted from 26 May to 30 June 2022 and a hospital evaluation dataset on quality of care. The use of m-PHR applications was measured by the number of m-PHR application downloads. Three independent variables were assessed: quality of care in the use of antibiotic drugs, injection drugs, and polypharmacy with ≥6 drugs. A generalized linear model was used for the analysis. The hospitals providing high-quality care, as evaluated based on the rate of antibiotic prescription (relative risk [RR], 3.328; 95% confidence interval [CI], 1.840 to 6.020; p < 0.001) and polypharmacy (RR, 2.092; 95% CI, 1.027 to 4.261; p = 0.042), showed an increased number of m-PHR downloads. Among the hospital covariates, public foundation status and being part of multi-hospital systems were associated with the number of m-PHR downloads (p < 0.05). This exploratory study found a positive relationship between quality of care and m-PHR use. Hospitals providing high-quality care may also excel in various activities, including m-PHR application use.

Factors influencing hip fracture surgery after two days of hospitalization using a national administrative database.

Globally, hip fractures represent a significant and growing public health concern, particularly as the elderly population increases. The timing for surgery following hospitalization for hip fractures is a crucial indicator of acute quality care following recommended surgical guidelines of within two days to minimize complications and mortality. However, factors influencing delayed surgery and its outcomes remain debated. This study, used a national administrative database in South Korea, aimed to examine surgery performed within two days of hospitalization and investigate factors affecting delayed surgical interventions and associated outcomes. Of the hip fracture patients analyzed, 40.6% underwent surgery within two days of hospitalization. Factors associated with delayed surgery included: male patients (OR 1.190; 95% CI 1.022 ~ 1.385), medical aid beneficiary (OR 1.385; 95% CI 1.120 ~ 1.713), higher comorbidity index (OR 1.365; 95% CI 1.163 ~ 1.603, OR 1.612, 95% CI 1.327 ~ 1.958), weekends admission (OR 2.384; 95% CI 2.804 ~ 2.729), admission via outpatient department (OR 1.298, 95% CI 1.071 ~ 1.574). ORIF (OR 0.823, 95% CI 0.691 ~ 0.980) was associated with a significantly low risk of late surgery. While early surgery did not significantly impact in-hospital mortality or complications, it was associated with short and postoperative lengths of stay. This study underscores the need for prompt surgical intervention, particularly in high-risk patient populations, as well as highlights the importance of further research to elucidate the relationship between the timing of surgery and postoperative outcomes.

A Bottom-Up Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Infliximab: Method Development, Comparison With 2 Enzyme-Linked Immunosorbent Assay Methods, and Evaluation of Anti-Drug Antibody Interference.

CONTEXT.­: Therapeutic drug monitoring is recommended to optimize infliximab use and improve outcome in chronic inflammatory disorders. OBJECTIVE.­: To describe a simple and affordable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure infliximab in serum. DESIGN.­: Infliximab was measured using winged stable isotope-labeled peptides as internal standards. Linearity, lower limit of measuring interval, limit of detection, precision, accuracy, carryover, and ion suppression were evaluated. Method comparison against 2 enzyme-linked immunosorbent assay (ELISA) methods (Remsima Monitor and IDKmonitor Infliximab) and anti-drug antibody (ADA) interference were evaluated using clinical specimens from inflammatory bowel disease patients (N = 237). RESULTS.­: Analytical run time and sample preparation time were 5 minutes per sample and 3 hours per batch, respectively. Analytical measurement interval and limit of detection were 0.50 to 50.0 µg/mL (R2 = 0.998) and 0.25 µg/mL, respectively. The intraday and interday imprecision percentage coefficients of variation were less than 6.1%. Accuracy was 94.2% to 98.7%. No significant ion suppression or carryover was observed. Infliximab concentrations measured by LC-MS/MS showed good agreement with those measured by Remsima Monitor (mean percentage difference, 5.7%; 95% CI, -1.2% to 12.6%) but were markedly lower than those measured by IDKmonitor (-32.6%; -35.8% to -29.4%), demonstrating significant bias between ELISAs. Although a good agreement between LC-MS/MS and ELISA was observed for ADA-negative samples (-3.5%; -12.8% to 5.9%), a significant bias was observed for ADA-positive samples (13.6%; 1.7% to 25.6%). CONCLUSIONS.­: This simple, fast, and affordable LC-MS/MS method for infliximab quantitation could improve standardization of infliximab quantitation and optimization of infliximab use in patients with high-titer ADA.

ASCL1-mediated direct reprogramming: converting ventral midbrain astrocytes into dopaminergic neurons for Parkinson's disease therapy.

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neurons development. [BMB Reports 2024; 57(8): 363-368].

An empirical study on social network analysis for small residential communities in Gangwon State, South Korea.

Social Network Analysis (SNA) provides a dynamic framework for examining interactions and connections within networks, elucidating how these relationships impact behaviors and outcomes. This study targeted small residential communities in Gangwon State, South Korea, to explore network formation theories and derive strategies for enhancing health promotion services in rural communities. Conducted in 12 small residential areas, the survey led to a network categorization model distinguishing networks as formal, informal, or non-existent. Key findings demonstrated that demographic and socio-economic factors, specifically age, income, living environment, leisure activities, and education level, significantly influence network formation. Importantly, age, environmental conditions, satisfaction with public transportation, and walking frequency were closely associated with the evolution of formal networks. These results highlight the importance of early community network assessments, which must consider distinct network traits to develop effective health promotion models. Utilizing SNA early in the assessment process can improve understanding of network dynamics and optimize the effectiveness of health interventions.

Therapeutic Drug Monitoring of 6 New-Generation Antiseizure Medications Using a Mass Spectrometry Method: Analysis of 2-Year Experience in a Large Cohort of Korean Epilepsy Patients.

CONTEXT.­: New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. OBJECTIVE.­: To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. DESIGN.­: Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. RESULTS.­: The method was linear with limit of detection less than 0.05 µg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs. CONCLUSIONS.­: A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.

Mental health of South Korean adolescents in the COVID-19 Era: Web-based survey focused on suicide-related factors.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted many aspects of life. Measures for preventing the spread of COVID-19 (e.g., school lockdowns, remote and hybrid classes, group and outdoor activity restrictions, and social distancing in the classroom and meal time) could have led to adolescents to experience anxiety and depressive symptoms. Such mental health impacts could increase the risk of suicidal ideation in this population. Moreover, according to a report by the Organization for Economic Co-operation and Development, although the total number of suicide deaths in South Korea decreased in 2021, the suicide rate of those aged 10-29 years increased. One factor affecting the result is adolescent mental health by COVID-19. This study examines the mental health status of South Korean adolescents amid the prolonged COVID-19 pandemic, and identifies and analyzes predictors of suicidal ideation, suicide planning, and suicide attempts. METHODS: The study used data from 54,948 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-based Survey. Based on their responses to suicide-related questions, the sample was divided into a healthy group, suicide-ideation group, suicide-planning group, and suicide-attempt group. The descriptive statistics of these groups were then analyzed. An analysis of covariance, post-hoc tests, and multiple logistic regression analysis were performed on the four groups. RESULTS: Overall, 6.9% of the participants reported suicidal ideation, 2.2% reported planning suicide, and 1.9% reported attempting suicide in the previous 12 months. CONCLUSIONS: During the prolonged COVID-19 pandemic, there is a strong need for various individualized programs that identify and intervene to support adolescents at risk of suicide by accurately assessing their mental health risk factors, such as stress, sadness and despair, loneliness, and generalized anxiety disorder. Accordingly, it is necessary to develop and distribute a mental health and well-being curriculum, strengthen suicide prevention programs and support services, expand mental health diagnostic tests, and school-based mental health programs.

Efficient Generation of Dopaminergic Neurons from Mouse Ventral Midbrain Astrocytes.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a wellknown neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

Reduced Cytotoxicity by Repetitive mRNA Transfection in Differentiated Neurons.

Background and Objectives: mRNA-based protein expression technology has been used to express functional proteins. We have previously generated dopamine neurons from rat-embryo derived neural precursor cells (NPCs) through repeated transfection of synthetic transcription factor mRNA encoding dopamine-inducible genes. However, NPCs began to die approximately 10 d post-transfection. In this study, we examined a long-term transfection protocol that did not affect cell viability. Methods and Results: Experiments were performed in eight groups sorted according to the start date of mRNA transfection. mRNA was transfected into NPCs daily for 21 d and live cell images of each group were recorded. NPCs which were differentiated for more than five days showed sustained gene expression and appreciable viability despite daily mRNA transfection for 21 d. Conclusions: Repeated mRNA transfection requires cells with a sufficient differentiation period.

Factors associated with the download and use of mobile personal health record applications in Korean hospitals.

The use of mobile personal health records (m-PHR) has been little studied at the organizational level. This study was to investigate the relationships of various hospital-related factors with m-PHR use in Korean hospitals. Downloads of m-PHR applications for 101 hospitals were examined from May 26 to 30 June 2022. The dependent variable was the number of m-PHR downloads, and the major independent variables included six technological, organizational, and environmental factors. As technological factors, the number of computed tomography and magnetic resonance imagery devices were significantly associated with downloads (RR = 1.119, CI = 1.022-1.226, p = 0.016; and RR = 1.155; 95% CI = 1.024-1.302, p = 0.019, respectively). At the organizational level, the number of physicians, adjusting for the number of beds, and the number of medical information management staff showed significant associations (RR = 1.059, CI = 1.019-1.100, p = 0.004; and RR = 1.026, CI = 1.002-1.050, p = 0.033, respectively). From an environmental standpoint, downloads were positively associated with the proportion of the local population of working age (20-59 years) (RR = 1.102, CI 1.022-1.189, p = 0.012). Healthcare policymakers should pay close attention to these factors to advocate for the widespread use of m-PHR applications.