Efficacy of the online Mindful Self-Compassion for Healthcare Communities program for surgical trainees: a prospective pilot study.

Purpose: The efficacy of the Mindful Self-Compassion (MSC) for Healthcare Communities program has not been verified. This study aims to evaluate the feasibility and efficacy of the online MSC for Healthcare Communities program on burnout, stress-related health, and resilience among surgical trainees. Methods: A single-arm pilot study was conducted at a tertiary referral academic hospital in Korea. Surgical trainees were recruited through flyer postings; therefore, a volunteer sample was used. Thus, 15 participants participated, among whom 9 were women and 11 were doctor-residents. The Self-Compassion for Healthcare Communities (SCHC) program was conducted from September to October 2021 via weekly online meetings (1 hour) for 6 weeks. The efficacy of the program was evaluated using validated scales for burnout, stress, anxiety, depression, self-compassion, and resilience before and after the intervention and 1 month later. Results: The results showed significantly reduced burnout, anxiety, and stress scores. After the program, high emotional exhaustion and depersonalization rates decreased, and personal accomplishment increased. Eight participants showed reduced anxiety postintervention, and 9 showed reduced stress. Improvements were observed between pre- and postintervention in resilience, life satisfaction, and common humanity. Changes in self-compassion predicted higher gains in resilience and greater reductions in burnout and stress. Conclusion: The SCHC is a feasible and effective program to improve resilience, self-compassion, and life satisfaction and reduce stress, anxiety, depression, and burnout in surgical trainees. This study highlights the need to include specific mental health programs in surgical training to improve trainees' well-being.

IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

COVID-19 Outbreak and Presymptomatic Transmission in Pilgrim Travelers Who Returned to Korea from Israel.

BACKGROUND: On February 21, 2020, 2 coronavirus disease 2019 (COVID-19) cases in pilgrim travelers from Korea to Israel were identified. We investigated the source of infection, clinical features of COVID-19, and transmission potential of presymptomatic and asymptomatic cases. METHODS: All 39 pilgrim travelers were aggressively tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their clinical features and possible source of infection were investigated by interview and review of their medical records. Ten confirmed cases without symptoms at the first sampling dates were selected for follow-up reverse transcription polymerase chain reaction tests. RESULTS: Of 39 pilgrim travelers, 30 (77%) were positive for SARS-CoV-2. Among the 30 positive COVID-19 cases, 4 (13%) were asymptomatic. Available follow-up cycle threshold values from 10 cases gradually increased over time and were lower during the presymptomatic period than during the postsymptomatic period. Out of 328 contacts related to the COVID-19 cases in the pilgrim travelers, 22 additional cases (7%) were confirmed with SARS-CoV-2 infections. Three tertiary cases were identified to be transmitted by presymptomatic secondary cases. CONCLUSION: To prevent transmission of COVID-19, we need to focus on presymptomatic and asymptomatic cases, and massive testing for SARS-CoV-2 is required. More research about the possibility of presymptomatic transmission over 2 days before symptom onset is required.

Rapid identification of unknown carboxyl esterase activity in Corynebacterium glutamicum using RNA-guided CRISPR interference.

RNA-guided genome engineering technologies have been developed for the advanced metabolic engineering of microbial cells to enhance production of value-added chemicals in Corynebacterium glutamicum as an industrial host. In this study, the RNA-guided CRISPR interference (CRISPRi) was applied to rapidly identify of unknown genes for native esterase activity in C. glutamicum. Combining with the carboxyl esterase (MekB) protein sequence alignment, two target genes (the cg0961 and cg0754) were selected for the CRISPRi application to investigate the possible native esterase in C. glutamicum. The recombinant strain with repressed expression of the cg0961 gene exhibited almost no capability on degradation of methyl acetate as a substrate of carboxyl esterase. This result was also confirmed in the cg0961 gene deletion mutant. Thus, we concluded that Cg0961 plays a major role of the native carboxyl esterase activity in C. glutamicum. In addition, CRISPRi demonstrated an application for gene identification and its function as another genetic tool for metabolic engineering in C. glutamicum.

RNA-guided single/double gene repressions in Corynebacterium glutamicum using an efficient CRISPR interference and its application to industrial strain.

BACKGROUND: The construction of microbial cell factories requires cost-effective and rapid strain development through metabolic engineering. Recently, RNA-guided CRISPR technologies have been developed for metabolic engineering of industrially-relevant host. RESULTS: To demonstrate the application of the CRISPR interference (CRISPRi), we developed two-plasmid CRISPRi vectors and applied the CRISPRi in Corynebacterium glutamicum to repress single target genes and double target genes simultaneously. Four-different single genes (the pyc, gltA, idsA, and glgC genes) repressions were successfully performed using the CRISPRi vectors, resulting significant mRNA reductions of the targets compared to a control. Subsequently, the phenotypes for the target gene-repressed strains were analyzed, showing the expected cell growth behaviors with different carbon sources. In addition, double gene repression (the idsA and glgC genes in a different order) by the CRISPRi resulted in an independent gene repression to each target gene simultaneously. To demonstrate an industrial application of the CRISPRi, citrate synthase (CS)-targeting DM1919 (L-lysine producer) strains with a sgRNA-gltA-r showed reduced CS activity, resulting in the improvement of L-lysine yield by 1.39-fold than the parental DM1919 (a lysine producer). CONCLUSIONS: Single or double gene repression were successfully performed using the CRISPRi vectors and sequence specific sgRNAs. The CRISPRi can be applied for multiplex metabolic engineering to enhanced lysine production and it will promote the further rapid development of microbial cell factories of C. glutamicum.

The survival effect of mitochondrial Higd-1a is associated with suppression of cytochrome C release and prevention of caspase activation.

Higd-1a (hypoxia induced gene domain family-1a) is a mitochondrial inner membrane protein with a conformation of N-terminal outside-C-terminal outside and loop inside. There are four Higd genes, Higd-1a, -1b, -1c and -2a, in the mouse. Higd-1a and -2a are expressed primarily in the brain, heart, kidney and leukocytes. HIF (hypoxia-inducible factor) overexpression induced the endogenous expression and promoter activity of Higd-1a. Mutation of the HRE (hypoxia-response element) site at -32bp in the Higd-1a promoter reduced the promoter activity, suggesting that transcription of Higd-1a is regulated by binding of the transcription factor HIF to the HRE. Higd-1a promoted cell survival under hypoxia. RAW264.7 cells stably transfected with Higd-1a underwent less apoptosis than control cells in a hypoxic condition, and hypoxia-induced apoptosis was strongly enhanced when endogenous Higd-1a was silenced by siRNA. The survival effect of Higd-1a was completely abolished by deletion of the 26 N-terminal amino acids, and we showed that Higd-1a increased survival by inhibiting cytochrome C release and reducing the activities of caspases. However, expression of Bcl-2, Bax, Bad, and BNIP3 and translocation of AIF were unaffected under the same conditions. Higd-2a also enhanced cell survival under hypoxia. Cells transfected with Higd-2a underwent less apoptosis than control cells in hypoxic conditions, and hypoxia-induced apoptosis increased when endogenous Higd-2a was depleted. Together these observations indicate that Higd-1a is induced by hypoxia in a HIF-dependent manner and its anti-apoptotic effect results from inhibiting cytochrome C release and reducing caspase activities.