Evaluation of Radiation Sensitivity Differences in Mouse Liver Tumor Organoids Using CRISPR/Cas9-Mediated Gene Mutation.

BACKGROUND: To assess the radiosensitivity of liver tumors harboring different genetic mutations, mouse liver tumors were generated in vivo through the hydrodynamic injection of clustered regularly interspaced short palindromic repeat/caspase 9 (CRISPR/Cas9) constructs encoding single-guide RNAs (sgRNAs) targeting Tp53, Pten, Nf1, Nf2, Tsc2, Cdkn2a, or Rb1. METHODS: The plasmid vectors were delivered to the liver of adult C57BL/6 mice via hydrodynamic tail vein injection. The vectors were injected into 10 mice in each group. Organoids were generated from mouse liver tumors. The radiation response of the organoids was assessed using an ATP cell viability assay. RESULTS: The mean survival period of mice injected with vectors targeting Nf2 (4.8 months) was lower than that of other mice. Hematoxylin and eosin staining, immunohistochemical (IHC) staining, and target sequencing analyses revealed that mouse liver tumors harbored the expected mutations. Tumor organoids were established from mouse liver tumors. Histological evaluation revealed marked morphological similarities between the mouse liver tumors and the generated tumor organoids. Moreover, IHC staining indicated that the parental tumor protein expression pattern was maintained in the organoids. The results of the ATP cell viability assay revealed that the tumor organoids with mutated Nf2 were more resistant to high-dose radiation than those with other gene mutations. CONCLUSIONS: This study developed a radiation response assessment system for mouse tumors with mutant target genes using CRISPR/Cas9 and organoids. The Tp53 and Pten double mutation in combination with the Nf2 mutation increased the radiation resistance of tumors. The system used in this study can aid in elucidating the mechanism underlying differential intrinsic radiation sensitivity of individual tumors.

Human Rights of Persons With Mental Illness After the Korean Mental Health Act Revision: A Qualitative Study.

After the Constitutional Court of Korea ruled that the provision of involuntary admissions was unconstitutional, as it violates personal freedom, the Mental Health and Welfare Act was amended in 2016. The current study explores involuntary admission and discharge experiences, after the law's revision, from a patient-centered perspective and suggests future directions to protect human rights. Data were collected from seven persons with mental illness and three family members through in-depth individual interviews and analyzed using thematic analysis. Persons with mental illness were still not guaranteed full autonomy and the right to receive proper treatment due to lack of mental health resources. The burden on family caregivers was amplified by stricter admission requirements. These results indicate the need for human rights-friendly emergency services, including peer crisis shelters and procedural assistance services. The government should develop community-based mental health services to ensure continuity of care without imposing public responsibility on family members. [Journal of Psychosocial Nursing and Mental Health Services, 60(8), 27-35.].

Effects of the Mental Health and Welfare Law revision on schizophrenia patients in Korea: an interrupted time series analysis.

BACKGROUND: High rates of involuntary hospitalization and long lengths of stay have been problematic in Korea. To address these problems, the Mental Health and Welfare Law was revised in 2016, mainly to protect patient rights by managing involuntary admissions. The aim of this study was to evaluate the impact of the revised Mental Health and Welfare Law on deinstitutionalization by using routinely collected data from hospital admissions and continuity of mental health service use after hospital discharge as proxy measures of deinstitutionalization. METHODS: We used monthly-aggregated claims-based data with a principal or secondary diagnosis of schizophrenia from 2012 to 2019, collected by the National Health Insurance Service. Outcome variables included rates of first admission; discharges; re-admissions within 7, 30, and 90 days; outpatient visits after discharge within 7 and 30 days; and continuity of visits, at least once a month for 6 months after discharge. Using interrupted time series analysis, we estimated the change in levels and trends of the rates after revision, controlling for baseline level and trend. RESULTS: There was no significant change in first admission and discharge rates after the revision. Immediately after the revision, however, the rates of re-admission within 7 and 30 days dropped significantly, by 2.24% and 1.99%, respectively. The slopes of the re-admission rate decreased significantly, by 0.10% and 0.14%, respectively. The slopes of the re-admission rate within 90 days decreased (0.001%). The rates of outpatient visits within 7 and 30 days increased by 1.98% and 2.72%, respectively. The rate of continuous care showed an immediate 4.0% increase. CONCLUSIONS: The revision had slight but significant effects on deinstitutionalization, especially decreasing short-term re-admission and increasing immediate outpatient service utilization.

Optical Filter-Embedded Fiber-Optic Radiation Sensor for Ultra-High Dose Rate Electron Beam Dosimetry.

FLASH radiotherapy is an emerging radiotherapy technique used to spare normal tissues. It employs ultra-high dose rate radiation beams over 40 Gy/s, which is significantly higher than those of conventional radiotherapy. In this study, a fiber-optic radiation sensor (FORS) was fabricated using a plastic scintillator, an optical filter, and a plastic optical fiber to measure the ultra-high dose rate electron beams over 40 Gy/s used in FLASH radiotherapy. The radiation-induced emissions, such as Cherenkov radiation and fluorescence generated in a transmitting optical fiber, were spectrally discriminated from the light outputs of the FORS. To evaluate the linearity and dose rate dependence of the FORS, the outputs of the fiber-optic radiation sensor were measured according to distances from an electron scattering device, and the results were compared with those of an ionization chamber and radiochromic films. Finally, the percentage depth doses were obtained using the FORS as a function of depth in a water phantom. This study found that ultra-high dose rate electron beams over 40 Gy/s could be measured in real time using a FORS.

Risk factors associated with surveillance loss after endoscopic submucosal dissection in patients with gastric neoplasm.

BACKGROUND: After endoscopic submucosal dissection of gastric neoplasms, surveillance endoscopy is required for patients with synchronous or metachronous neoplasms. We aimed to evaluate the risk factors associated with surveillance loss in patients who underwent endoscopic submucosal dissection. METHODS: Ninety-five patients treated with endoscopic submucosal dissection for gastric neoplasms between May 2015 and June 2016 were retrospectively reviewed. Clinicopathologic factors, sociodemographic factors, psychiatric measures, and associated risk factors for surveillance loss were evaluated. The chi-square or Fisher exact test, t-test, and logistic regression analysis were used in data analysis. RESULTS: Twenty-five (26.3%) patients were identified as having surveillance loss. Compared to the surveillance group, the surveillance loss group was old and had dysplasia, and a healthy American Society of Anesthesiologists physical status. Similarly, surveillance loss was related to low symptom perception, low incidence of alexithymia, mindful awareness, and high trait forgiveness. Logistic regression analysis showed that dysplasia (odds ratio, 15.23; 95% CI, 1.56-149.09, P=0.019), old age (odds ratio, 7.14; 95% CI, 1.90-26.88, P=0.004), and American Society of Anesthesiologists physical status 1 (odds ratio, 3.99; 95% CI, 1.09-14.60, P=0.037) were associated with surveillance loss. CONCLUSIONS: Dysplasia, old age, and the American Society of Anesthesiologists physical status 1 were associated with surveillance loss in patients who underwent gastric endoscopic submucosal dissection. It could be helpful to proactively monitor patients with such conditions after gastric endoscopic submucosal dissection.

Measurement of Switching Performance of Pixelated Silicon Sensor Integrated with Field Effect Transistor.

Silicon shows very high detection efficiency for low-energy photons, and the silicon pixel sensor provides high spatial resolution. Pixelated silicon sensors facilitate the direct detection of low-energy X-ray radiation. In this study, we developed junction field effect transistors (JFETs) that can be integrated into a pixelated silicon sensor to effectively handle many signal readout channels due to the pixelated structure without any change in the sensor resolution; this capability of the integrated system arises from the pixelated structure of the sensor. We focused on optimizing the JFET's switching function, and simulated JFETs with different fabrication parameters. Furthermore, prototype JFET switches were designed and fabricated on the basis of the simulated results. It is important not only to keep the low leakage currents in the JFET but also reduce the current flow as much as possible by providing a high resistance when the JFET switch is off. We determined the optimal fabrication conditions for the effective switching of the JFETs. In this paper, we present the results of the measurement of the switching capability of the fabricated JFETs for various design variables and fabrication conditions.

Poverty in the midst of plenty: unmet needs and distribution of health care resources in South Korea.

BACKGROUND: The unmet needs for health care have been used as an alternative measurement to monitor equity in health services. We sought to examine contextual influences on unmet needs for health care whereas precedent studies have been focused on individual characteristics on them. METHODS AND FINDINGS: The current study conducted multilevel logistic regression analysis to assess the effects of individual- and contextual-level predictors in meeting individual health care needs in South Korea. We sampled 7,200 individuals over the age of 19 in the Fourth Korea National Health and Nutrition Examination Survey in 2009. Included in the regression model were individual predictors such as demographic variables, socio-economic status, and self-rated health; the density of beds and physicians in public and private sectors within different regions were used as contextual-level predictors. This study showed the inverse association between unmet needs and regional resources in private sectors after controlling for the effects of individual-level predictors. CONCLUSION: Our findings suggest that increasing regional resources in private sectors might produce inefficiency in the health care system and inequity in access to health services, particularly where the competition in private health care sectors was highly stimulated under the fee-for-service reimbursement scheme. Policies for the reallocation of health care resources and for reduction of individual health care costs are needed in Korea.