Since its discovery, the Clustered Regularly Interspaced Short Palindromic Repeat (the CRISPR) system has been increasingly applied to therapeutic genome editing. Employment of several viral and ...non-viral vectors has enabled efficient delivery of the CRISPR system to target cells or tissues. In addition, the CRISPR system is able to modulate the target gene’s expression in various ways, such as mutagenesis, gene integration, epigenome regulation, chromosomal rearrangement, base editing and mRNA editing. However, there are still limitations hindering an ideal application of the system: inefficient delivery, dysregulation of the delivered gene, the immune response against the CRISPR system, the off-target effects or the unintended on-target mutations. In addition, there are recent discoveries that have not been yet applied to CRISPR-mediated therapeutic genome editing. Here, we review the overall principles related to the therapeutic application of the CRISPR system, along with new strategies for the further application and prospects to overcome the limitations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
한국과 일본의 노인 대상 지역사회 재활서비스 비교 연구: 노인장기요양보험 제도를 중심으로 이민영; Minyoung Lee
Han'guk Chŏnmun Mulli Ch'iryo Hakhoe chi = Journal of the Korean Academy of University Trained Physical Therapists,
05/2022, Volume:
29, Issue:
2
Journal Article
Open access
Background: As South Korea enters an aged society, the government has emphasized the need for a soft landing of the older adults into the community after the acute and recovery periods under a ...national policy of “community care.” However, the institutionalization of community rehabilitation services to implement this is insufficient. Japan had already entered an aged society when the Long-Term Care Insurance System was introduced in 2000. Thus, the case of Japan’s institutionalization of the system is expected to have implications for us in supplementing a suitable system for the aged society.
Objects: This study compared the institutionalization process of the Long-Term Care Insurance System in South Korea and Japan and the services currently being implemented in each country.
Methods: To examine the institutionalization process and services of the system, related legal rules and regulations, government reports, and articles were reviewed. To examine the operation status of the system, statistical data provided by each country’s government were analyzed.
Results: Japan recognized the importance of community rehabilitation even before the enactment of Long-Term Care Insurance. Thus, community rehabilitation services, such as home-visit rehabilitation and health facilities, were already stipulated in the law. Under such institutional legacy, Long-Term Care Insurance was able to establish a service system, which balanced welfare and health-related services, including various types of services with enhanced rehabilitation functions. In South Korea, rehabilitation policies were not much considered in the process of institutionalizing the system; thus, it was composed mainly of services focusing on care and recuperation.
Conclusion: In order to realize community care, rehabilitation services need to be developed in Long-Term Care Insurance System in various forms such as home-visit services, daily services, short stay, and facility services.
Various torque distribution and stability control algorithms have been studied along with the development of four-wheel drive vehicles. But, most of those algorithms focus only on performance ...improvement. Since the independent four-wheel drive system is based on four drive motors, faults can occur in a motor or an inverter. If a fault occurs, the vehicle stability is not guaranteed and a fatal accident can occur. In this study, the fault-tolerant stability control algorithm for remaining healthy motors is proposed. This fault-tolerant control (FTC) system contains torque distribution and stability control algorithms. For accurate control of motor allocation, driving conditions such as under/over-steering, and steering direction should be considered, as well as vehicle condition such as fault motor location and motor performance limits. The proposed FTC is evaluated with two fault conditions (e.g., front motor fault, rear motor fault) under straight acceleration and constant steering acceleration scenarios. The behavior characteristics and driving risks caused by failures of motors while driving are analyzed. Also, the FTC algorithm is accurately follow a desired path within a minimum error range that the driver can cover.
The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus ...rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).
A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.
Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104).
Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.
The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The circadian clock synchronizes biological processes to daily cycles of light and temperature. Clock components, including CIRCADIAN CLOCK-ASSOCIATED1 (CCA1), are also associated with cold ...acclimation. However, it is unknown how CCA1 activity is modulated in coordinating circadian rhythms and cold acclimation. Here, we report that self-regulation of Arabidopsis thaliana CCA1 activity by a splice variant, CCA1β, links the clock to cold acclimation. CCA1β interferes with the formation of CCA1α-CCA1α and LATE ELONGATED HYPOCOTYL (LHY)-LHY homodimers, as well as CCA1α-LHY heterodimers, by forming nonfunctional heterodimers with reduced DNA binding affinity. Accordingly, the periods of circadian rhythms were shortened in CCA1β-overexpressing transgenic plants (35S:CCA1β), as observed in the cca1 lhy double mutant. In addition, the elongated hypocotyl and leaf petiole phenotypes of CCA1α-overexpressing transgenic plants (35S:CCA1α) were repressed by CCA1β coexpression. Notably, low temperatures suppressed CCA1 alternative splicing and thus reduced CCA1β production. Consequently, whereas the 35S:CCA1α transgenic plants exhibited enhanced freezing tolerance, the 35S:CCA1β transgenic plants were sensitive to freezing, indicating that cold regulation of CCA1 alternative splicing contributes to freezing tolerance. On the basis of these findings, we propose that dynamic self-regulation of CCA1 underlies the clock regulation of temperature responses in Arabidopsis.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass ...index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, −0.75 kg/m2; 95% CI, −1.44 to −0.06), fasting glucose level (WMD, −4.16 mg/dL; 95% CI, −6.92 to −1.40), and homeostatic model assessment of insulin resistance (WMD, −0.54; 95% CI, −1.05 to −0.03). Fat mass (WMD, −0.98 kg; 95% CI, −2.32 to 0.36) tended to decrease in the IFD group with a significant increase in adiponectin (WMD, 1008.9 ng/mL; 95% CI, 140.5 to 1877.3) and a decrease in leptin (WMD, −0.51 ng/mL; 95% CI, −0.77 to −0.24) levels. An IFD may provide a significant metabolic benefit by improving glycemic control, insulin resistance, and adipokine concentration with a reduction of BMI in adults.
As digital health services advance, digital health equity has become a significant concern. However, people with disability and older adults still face health management limitations, particularly in ...the COVID-19 pandemic. An essential area of investigation is proposing a patient-centered design strategy that uses patient-generated health data (PGHD) to facilitate optimal communication with caregivers and health care service providers.
This study aims to conceptualize, develop, and validate a digitally integrated health care service platform for people with disability, caregivers, and health care professionals, using Internet of Things devices and PGHD to contribute to improving digital health equity.
The methodology consists of 5 stages. First, a collaborative review of the previous app, Daily Healthcare 1.0, was conducted with individuals with disabilities, caregivers, and health care professionals. Secondly, user needs were identified via personas, scenarios, and user interface sketches to shape a user-centered service design. The third stage created an enhanced app that integrated these specifications. In the fourth stage, heuristic evaluations by clinical and app experts paved the way for Daily Healthcare 2.0, now featuring Internet of Things device integration. Conclusively, in the fifth stage, an extensive 2-month usability evaluation was executed with user groups comprising individuals with disabilities using the app and their caregivers.
Among the participants, "disability welfare information and related institutional linkage" was the highest priority. Three of the 14 user interface sketches the participants created were related to "providing educational content." The 11 heuristic evaluation experts identified "focusing on a single task" as a crucial issue and advocated redesigning the home menu to simplify it and integrate detailed menus. Subsequently, the app Daily Healthcare 2.0 was developed, incorporating wearable devices for collecting PGHD and connecting individuals with disabilities, caregivers, and health care professionals. After the 2-month usability evaluation with 27 participants, all participants showed an increase in eHealth literacy, particularly those who used the caregiver app. Relatively older users demonstrated improved scores in health IT usability and smartphone self-efficacy. All users' satisfaction and willingness to recommend increased, although their willingness to pay decreased.
In this study, we underscore the significance of incorporating the distinct needs of individuals with disabilities, caregivers, and health care professionals from the design phase of a digital health care service, highlighting its potential to advance digital health equity. Our findings also elucidate the potential benefits of fostering partnerships between health consumers and providers, thereby attenuating the vulnerability of marginalized groups, even amid crises such as the COVID-19 pandemic. Emphasizing this imperative, we advocate for sustained endeavors to bolster the digital literacy of individuals with disabilities and champion collaborative cocreation, aiming to uphold the collective ethos of health and digital health equity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Allium ulleungense (AU) and A. microdictyon (AM) are valuable medicinal and edible vegetables, referred to as mountain garlic in Korea. The identification of AU, AM and a neighboring species A. ...ochotense (AO) is difficult because of their morphological similarities. We collected samples from three species and 46 cultivated collections to understand the genetic diversity of these valuable Allium species. Among them, we sequenced six collections, including three species and three cultivating collections to obtain data from the plastid genome (plastome) and nuclear 45S ribosomal DNA (nrDNA) for super-barcoding. The AM and AO showed around 60 single nucleotide polymorphisms (SNPs) and 39 Insertion/Deletion (InDels) in the plastome but no variations in the nrDNA sequences. Conversely, the AU and AM showed more than 170 SNPs and 80 InDels in the plastomes, and 20 SNPs and 1 InDel were found in the 45S nrDNA sequences. Among the three cultivating collections, one TB collection was determined to be the AU type in both plastome and nrDNA sequences. However, the other two collections, JB and SA, showed the AM type plastome but were heterozygous in the 45S nrDNA sequences, indicating both AU and AM types (putative AM x AU hybrid). Ten molecular markers were developed based on sequence variations to identify these three species and assess their genetic diversity. A total of 49 collections were genotyped using the ten developed markers and classified into five groups: 14 AU, 22 AM, 1 AO, 3 putative AM x AU hybrids, and 9 putative AU x AM hybrid collections. Super-barcoding with plastomes and nrDNAs revealed the genetic diversity of the three Allium species and putative hybrids between species. The newly developed markers will facilitate species and hybrid identification, thereby benefiting marker-assisted molecular breeding of Allium species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: As South Korea enters an aged society, the government has emphasized the need for a soft landing of the older adults into the community after the acute and recovery periods under a ...national policy of “community care.” However, the institutionalization of community rehabilitation services to implement this is insufficient. Japan had already entered an aged society when the Long-Term Care Insurance System was introduced in 2000. Thus, the case of Japan’s institutionalization of the system is expected to have implications for us in supplementing a suitable system for the aged society.Objects: This study compared the institutionalization process of the Long-Term Care Insur-ance System in South Korea and Japan and the services currently being implemented in each country.Methods: To examine the institutionalization process and services of the system, related legal rules and regulations, government reports, and articles were reviewed. To examine the operation status of the system, statistical data provided by each country’s government were analyzed.Results: Japan recognized the importance of community rehabilitation even before the en-actment of Long-Term Care Insurance. Thus, community rehabilitation services, such as home-visit rehabilitation and health facilities, were already stipulated in the law. Under such institu-tional legacy, Long-Term Care Insurance was able to establish a service system, which balanced welfare and health-related services, including various types of services with enhanced reha-bilitation functions. In South Korea, rehabilitation policies were not much considered in the process of institutionalizing the system; thus, it was composed mainly of services focusing on care and recuperation. Conclusion: In order to realize community care, rehabilitation services need to be developed in Long-Term Care Insurance System in various forms such as home-visit services, daily services, short stay, and facility services.
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