In vivo magnetogenetics for cell-type-specific targeting and modulation of brain circuits.

Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals.

Ten-year trends of antibiotics used for patients with pneumonia at long-term care hospitals in the Republic of Korea: An analysis based on national health insurance claims data.

Aim: To determine the trends in the usage of antimicrobial drugs by patients with pneumonia with prescriptions from long-term care (LTC) hospitals in the Republic of Korea. Method: This retrospective study was conducted from 2011 to 2022 using the National Health Insurance Review and Assessment Service claim data in Korea. We calculated antibiotic usage expressed as a daily defined dose (DDD) per 1000 patients per day (DID). Results: The number of patients with pneumonia in LTC hospitals increased by 2.7 times, from 30,000 in 2011 to 79,000 in 2022. Furthermore, antibiotic consumption per episode by patients with pneumonia in LTC hospitals increased from 17.14 DDD in 2011 to 18.11 DDD in 2022. Among the Access, Watch, and Reserve classification groups, the Watch group showed the highest usage; further, the Access group showed a decreasing trend, whereas the Watch and Reserve groups showed an increasing trend (p < 0.01). In the Watch group, the most commonly used antibiotic was J01CR05 (piperacillin and beta-lactamase inhibitor), followed in order by J01DD04 (ceftriaxone), J01MA12 (levofloxacin), and J01DH02 (meropenem). In the Reserve group, J01XB01 (colistin) and J01AA12 (tigecycline) were commonly used. Conclusion: The antibiotics prescribed for pneumonia in LTC hospitals have continuously increased the use of broad-spectrum antibiotics. Accordingly, appropriate use of antibiotics in LTC hospital settings and assessment of antibiotics used are warranted.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Characterization and Spike Gene Analysis of a Candidate Attenuated Live Bovine Coronavirus Vaccine.

The bovine coronavirus (BCoV) KBR-1 strain, obtained from calf diarrhea samples collected in 2017, belongs to group GIIa. To attenuate this strain, it was subcultured continuously (up to 79 times) in HRT-18 cells, followed by 80-120 passages in MDBK cells. The KBR-1-p120 strain harvested from MDBK cells at passage 120 harbored 13 amino acid mutations in the spike gene. Additionally, the KBR-1-p120 strain showed a high viral titer and cytopathogenic effects in MDBK cells. Seven-day-old calves (negative for BCoV antigen and antibodies) that did not consume colostrum were orally inoculated with the attenuated candidate strain (KBR-1-p120), or with KBR-1 passaged 10 times (KBR-1-p10) in HRT-18 cells. Calves inoculated with KBR-1-p10 had a low diarrhea score, and BCoV RNA was detected at 3-7 days post-inoculation (DPI). The virus was also present in the duodenum, jejunum, and ileum at autopsy; however, calves inoculated with KBR-1-p120 had low levels of BCoV RNA in feces at 4-6 DPI, and no diarrhea. In addition, an extremely small amount of BCoV RNA was present in the jejunum and ileum at autopsy. The small intestines of calves inoculated with KBR-1-p120 were emulsified and used to infect calves two more times, but pathogenicity was not recovered. Therefore, the KBR-1-p120 strain has potential as a live vaccine candidate.

Impact of coronavirus disease 2019 on cancer care: How the pandemic has changed cancer utilization and expenditures.

PURPOSE: Since identified in December 2019, the novel coronavirus disease 2019 (COVID-19) has had a global impact on medical resource use and costs for patients with cancer in South Korea. This study aimed to identify the medical use and costs among patients with cancer during the COVID-19 pandemic, to predict these patterns in South Korea in the future. METHODS: We conducted a secondary claims data analysis using the National Health Insurance Service database for the calendar period of 2019-2020. Monthly relative percent changes in cancer incidence, medical use, and billing costs for medical care utilization by cancer type were calculated. Then, the medical use and costs after January 2020 were predicted using a time series model with data before the COVID-19 outbreak (2014-2019). RESULTS: The incidence of cancer diagnoses has seen a notable decline since the outbreak of the COVID-19 in 2020 as compared to 2019. Despite the impact of COVID-19, there hasn't been a distinct decline in outpatient utilization when compared to inpatient utilization. While medical expenses for both inpatient and outpatient visits have slightly increased, the number of patients treated for cancer has decreased significantly compared to the previous year. In June 2020, overall outpatient costs experienced the highest increase (21.1%), while individual costs showed the most significant decrease (-4.9%) in June 2020. Finally, the number of hospitalisations and outpatient visits increased slightly from June-July in 2020, reducing the difference between the actual and predicted values. The decrease in the number of inpatient hospitalisations (-22~-6%) in 2020 was also high. CONCLUSIONS: The overall use of medical services by patients with cancer decreased in 2020 compared with that in the pre-COVID-19 pandemic period. In the future, the government should consider how to recover from the COVID-19 pandemic, and establish permanent health policies for patients with cancer.