The coronavirus disease (COVID-19) pandemic has posed a challenge for healthcare systems, and healthcare workers (HCWs) are at high risk of exposure. Protecting HCWs is of paramount importance to ...maintain continuous patient care and keep healthcare systems functioning. Used alongside administrative and engineering control measures, personal protective equipment (PPE) is the last line of defense and the core component of protection. Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly transmitted through respiratory droplets and close contact. Airborne transmission may occur during aerosol-generating procedures. However, the modes of transmission still remain uncertain, especially regarding the possibility of airborne transmission when aerosol-generating procedures are not performed. Thus, there are some inconsistencies in the respiratory protective equipment recommended by international and national organizations. In Korea, there have been several modifications to PPE recommendations offering options in choosing PPE for respiratory and body protection, which confuses HCWs; they are often unsure what to wear and when to wear it. The choice of PPE is based on the risk of exposure and possible modes of transmission. The level of protection provided by PPE differs based on standards and test methods. Thus, understanding them is the key in selecting the proper PPE. This article reviews evidence on the mode of SARS-CoV-2 transmission, compares the current PPE recommendations of the World Health Organization with those in Korea, and discusses standard requirements and the proper selection of PPE.
Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising ...therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models.
Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice.
PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice.
PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.
Programmed cell death‐ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single‐chain fragment of variable domain ...(scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof‐of‐concept data for the effect of scFv using PDL1‐expressing cells was lacking. In this study, we conducted two kinds of cell‐based immunoassays, western blotting and enzyme‐linked immunosorbent assay, using anti‐PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell‐based immunoassays to detect PDL1.
Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to ...minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.
Achieving a deep molecular response (DMR) to tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) remains challenging and at present, there is no biomarker to predict DMR in ...this setting. Herein, we report that an HMGCLL1 genetic variant located in 6p12.1 can be used as a predictive genetic biomarker for intrinsic sensitivity to imatinib (IM) therapy. We measured DMR rate according to HMGCLL1 variant in a discovery set of CML patients (n = 201) and successfully replicated it in a validation set (n = 270). We also investigated the functional relevance of HMGCLL1 blockade with respect to response to TKI therapy and showed that small interfering RNA mediated blockade of HMGCLL1 isoform 3 results in significant decrease in viability of BCR-ABL1-positive cells including K562, CML-T1 or BaF3 cell lines with or without ABL1 kinase domain mutations such as T315I mutation. Decreased cell viability was also demonstrated in murine CML stem cells and human hematopoietic progenitor cells. RNA sequencing showed that blockade of HMGCLL1 was associated with G0/G1 arrest and the cell cycle. In summary, the HMGCLL1 gene polymorphism is a novel genetic biomarker for intrinsic sensitivity to IM therapy in CML patients that predicts DMR in this setting.
The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation ...process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application. We report that that a single transfer of embryonic stem (ES) cell–derived proteins into primarily cultured adult mouse fibroblasts, rather than repeated transfer or prolonged exposure to materials, can achieve full reprogramming up to the pluripotent state without the forced expression of ectopic transgenes. During the process, gene expression and epigenetic status were converted from somatic to ES-equivalent status. We verified that protein-based reprogramming was neither by the contamination of protein donor ES cell nor by DNA/RNA from donor ES cell. Protein-iPS cells were biologically and functionally very similar to ES cells and differentiated into 3 germ layers in vitro. Furthermore, protein-iPS cells possessed in vivo differentiation (well-differentiated teratoma formation) and development (chimeric mice generation and a tetraploid blastocyst complementation) potentials. Our results provide an alternative and safe strategy for the reprogramming of somatic cells that can be used to facilitate pluripotent stem cell–based cell therapy.
Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 ...(LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival under glucose deprivation. Thus, depending on glucose availability, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.
Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on ...the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.
To identify emergency department triage accuracy using the Korean Triage and Acuity Scale (KTAS) and evaluate the causes of mistriage.
This cross-sectional retrospective study was based on 1267 ...systematically selected records of adult patients admitted to two emergency departments between October 2016 and September 2017. Twenty-four variables were assessed, including chief complaints, vital signs according to the initial nursing records, and clinical outcomes. Three triage experts, a certified emergency nurse, a KTAS provider and instructor, and a nurse recommended based on excellent emergency department experience and competence determined the true KTAS. Triage accuracy was evaluated by inter-rater agreement between the expert and emergency nurse KTAS scores. The comments of the experts were analyzed to evaluate the cause of triage error. An independent sample t-test was conducted to compare the number of patient visits per hour in terms of the accuracy and inaccuracy of triage.
Inter-rater reliability between the emergency nurse and the true KTAS score was weighted kappa = .83 and Pearson's r = .88 (p < .001). Of 1267 records, 186 (14.7%) showed some disagreement (under triage = 131, over triage = 55). Causes of mistriage included: error applying the numerical rating scale (n = 64) and misjudgment of the physical symptoms associated with the chief complaint (n = 47). There was no statistically significant difference in the number of patient visits per hour for accurate and inaccurate triage (t = -0.77, p = .442).
There was highly agreement between the KTAS scores determined by emergency nurses and those determined by experts. The main cause of mistriage was misapplication of the pain scale to the KTAS algorithm.
Cancer stem cells (CSCs) play a pivotal role in cancer relapse or metastasis. We investigated the CSC‐suppressing effect of nonsteroidal anti‐inflammatory drugs (NSAIDs) and the relevant mechanisms ...in colorectal cancer. We measured the effect of NSAIDs on CSC populations in Caco‐2 or SW620 cells using colosphere formation and flow cytometric analysis of PROM1 (CD133)+CD44+ cells after indomethacin treatment with/without prostaglandin E2 (PGE2) or peroxisome proliferator‐activated receptor γ (PPARG) antagonist, and examined the effect of indomethacin on transcriptional activity and protein expression of NOTCH/HES1 and PPARG. These effects of indomethacin were also evaluated in a xenograft mouse model. NSAIDs (indomethacin, sulindac and aspirin), celecoxib, γ‐secretase inhibitor and PPARG agonist significantly decreased the number of colospheres formation compared to controls. In Caco‐2 and SW620 cells, compared to controls, PROM1 (CD133)+CD44+ cells were significantly decreased by indomethacin treatment, and increased by 5‐fluorouracil (5‐FU) treatment. This 5‐FU‐induced increase of PROM1 (CD133)+CD44+ cells was significantly attenuated by combination with indomethacin. This CSC‐inhibitory effect of indomethacin was reversed by addition of PGE2 and PPARG antagonist. Indomethacin significantly decreased CBFRE and increased PPRE transcriptional activity and their relative protein expressions. In xenograft mouse experiments using 5‐FU‐resistant SW620 cells, the 5‐FU treatment combined with indomethacin significantly reduced tumor growth, compared to 5‐FU alone. In addition, treatment of indomethacin alone or combination of 5‐FU and indomethacin decreased the expressions of PROM1 (CD133), CD44, PTGS2 (cyclooxygenase 2) and HES1, and increased PPARG expression. NSAIDs could selectively reduce the colon CSCs and suppress 5‐FU‐induced increase of CSCs via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating PPARG.
What's new?
Cancer stem cells (CSCs) may play a pivotal role in tumor recurrence and resistance to chemotherapy. For example, CSCs are enriched in residual tumors following conventional chemotherapy. In this study, the authors found that nonsteroidal anti‐inflammatory drugs (NSAIDs) could selectively reduce colon CSCs, by inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating PPARG. NSAIDs also suppressed chemotherapy‐induced increases of CSCs in a mouse xenograft model of colorectal cancer (CRC). NSAIDs may thus provide a promising adjunct to standard chemotherapy, decreasing tumor recurrence and improving survival in CRC.
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