In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

The Impact of National Health Insurance Coverage on Compliance With Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea.

OBJECTIVES: Compliance with positive airway pressure (PAP) in patients with obstructive sleep apnea (OSA) directly affects its treatment efficacy. Since July 2018, polysomnography and PAP therapy have been covered by the National Health Insurance (NHI), which has reduced the price barrier and promoted PAP therapy in Korea. This study aimed to compare changes in PAP compliance before and after NHI implementation. METHODS: This study is a retrospective analysis in a tertiary hospital setting in Korea. From 2011 to 2019, patients with OSA (apnea-hypopnea index ≥5) treated using a PAP device for ≥1 month were included. They were classified as belonging to the pre-insurance (PI) group (having started PAP before July 2018) or the NHI group (having received a PAP reimbursement by the NHI service). We collected and analyzed medical records and PAP use information for between-group comparisons of compliance. We defined compliance as the percentage of usage days, the percentage of days with usage for ≥4 night hours, and average daily usage hours. RESULTS: We included 146 and 100 patients in the PI and NHI groups, respectively. Automatic PAP mode and NHI were independent predictors of compliance B at the 3- and 9-month follow-up points. The NHI group showed significantly higher compliance A at 3, but not 9 months. For compliance B, the NHI group showed significantly higher compliance than the PI group at 1 month and 3 months, but not at 9 months. Compared with the PI group, the NHI group showed significantly higher compliance C only at 3 months. CONCLUSION: The NHI has positively affected PAP therapy in patients with OSA. Insurance policy may affect compliance within the first 3 months of PAP therapy.

Photobiomodulation as an antioxidant substitute in post-thawing trauma of human stem cells from the apical papilla.

Cryopreservation, the most common method of preserving stem cells, requires post-processing because it produces trauma to the cells. Post-thawing trauma typically induces cell death, elevates reactive oxygen species (ROS) concentration, and lowers mitochondrial membrane potential (MMP). Although this trauma has been solved using antioxidants, we attempted to use photobiomodulation (PBM) instead of chemical treatment. We used a 950-nm near-infrared LED to create a PBM device and chose a pulsed-wave mode of 30 Hz and a 30% duty cycle. Near-infrared radiation (NIR) at 950 nm was effective in reducing cell death caused by hydrogen peroxide induced-oxidative stress. Cryodamage also leads to apoptosis of cells, which can be avoided by irradiation at 950 nm NIR. Irradiation as post-processing for cryopreservation had an antioxidant effect that reduced both cellular and mitochondrial ROS. It also increased mitochondrial mass and activated mitochondrial activity, resulting in increased MMP, ATP generation, and increased cytochrome c oxidase activity. In addition, NIR increased alkaline phosphatase (ALP) activity, a biomarker of differentiation. As a result, we identified that 950 nm NIR PBM solves cryodamage in human stem cells from the apical papilla, indicating its potential as an alternative to antioxidants for treatment of post-thawing trauma, and further estimated its mechanism.

Reliability and validity of the Korean version of the comprehensive assessment of at-risk mental states.

AIM: Although the comprehensive assessment of at-risk mental states (CAARMS) is one of the most widely used instruments for identifying individuals meeting the criteria for ultra-high risk (UHR) of developing psychosis, the psychometric properties of the Korean version of the CAARMS (CAARMS-K) have not been studied to date. Thus, we tested the reliability, validity, and factor structure of the CAARMS-K in a Korean population. METHODS: The CAARMS-K was administered to 96 UHR individuals. The inter-rater reliability and internal consistency of the CAARMS-K were evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was examined by comparing the extracted CAARMS-K factors with the five factors of the positive and negative syndrome scale (PANSS) using Spearman's correlation tests. The percentage of transition to psychosis was examined at 1- and 2-year. RESULTS: The inter-rater reliability was good (intraclass correlation = .89), and the internal consistency was acceptable (Cronbach's alpha = .812). A five-factor solution demonstrated the best simple structure and accounted for 43.1% of all-item variance. The five factors extracted from the factor analysis were similar to the PANSS five factors and significantly correlated with the factors of the PANSS. Among the 96 UHR individuals, 11 (11.5%) and 17 (17.7%) developed psychotic disorders during the 1- and 2-year follow-up, respectively. CONCLUSIONS: The CAARMS-K is a reliable and valid instrument for the assessment of UHR individuals in Korea.

Identification of an autosomal dominant locus for intracranial aneurysm through a model-based family collection in a geographically limited area.

Intracranial aneurysm (IA) is characterized by an abnormal bulging of one of the arteries in the brain and is heavily affected by genetic factors. Although IA is a very serious disease because of its severity and prevalence in the general public, the gene causing IA has not yet been identified due mainly to the lack of definitive genetic loci for the disease. Following a model-based family collection that recruited families from a geographically limited area that inherited IA as an autosomal dominant trait, we conducted a genome-wide linkage analysis. Significant evidence of linkage to IA was found on chromosome 8p22.2 with a maximum two-point logarithm of the odds ratio score of 3.61 under an autosomal dominant model of inheritance. The methods described in this study could be applied to localize disease-causing genes of other complex diseases through either a genome-wide linkage analysis or a genome-wide association study.