Comparison of Positive/Inconclusive Xpert Xpress SARS-CoV-2 with the Standard M nCoV Real-Time Detection.

BACKGROUND: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be diagnosed using rapid real-time PCR, real-time reverse transcription PCR (rRT-PCR), or rapid antigen testing. Among these, rRT-PCR is considered the gold standard assay. The Xpert Xpress SARS-CoV-2 assay is a rapid real-time PCR test, approved by the Korean Disease Control and Prevention Agency in 2020. The overall concordance and positive concordance rates of the Xpert assay with the STANDARD M nCoV Real-Time Detection kit were determined. METHODS: All samples with positive or inconclusive Xpert test results from July 2021 to February 2023 that underwent confirmatory testing using the reference rRT-PCR assay were included in the analysis. RESULTS: Samples from 224 patients (93 men and 131 women) with a median age of 59 years (range 15 - 90 years) were included. Of 212 samples that tested positive using Xpert, 112 (52.8%) were true positves and 100 (47.2%) were false positives on rRT-PCR testing. The overall concordance and positive concordance rates were 52.8% (112/212) and 54.5% (112/224), respectively. In the Xpert positive group, the samples had a lower Ct value for the E gene than the N2 gene. The Ct values for the E and N2 genes were significantly lower in the positive group than in the inconclusive group. CONCLUSIONS: Positive or inconclusive Xpert results should be confirmed by the gold standard rRT-PCR for early control of this disease. Furthermore, Korea's policy should be reconsidered given the high false-positive rate of the rapid real-time PCR Xpert Xpress SARS-CoV-2 assay.

Effect of the copayment reduction system on accessibility to orphan drugs in South Korea.

OBJECTIVE: This study aims to analyze the effect of the copayment reduction system on accessibility to orphan drugs (ODs) in South Korea. METHODS: Data on approval and reimbursement for drugs designated as ODs for the last 10 years (2012-2021) in South Korea were extracted. Among them, with 136 approved products as of 31 December 2022, the reimbursement rates and lead time to reimbursement between drugs for rare diseases (DRDs) and nondrugs for rare diseases (non-DRDs) were analyzed. The pricing and reimbursement (P&R) pathways between drugs for only rare diseases (DORDs) and drugs for rare and cancerous diseases (DRCDs) were compared. RESULTS: The reimbursement rates for DRDs and non-DRDs were 54.8% and 33.3%, respectively, and the lead time to reimbursement for DRDs and non-DRDs were 16.1 months and 31.2 months, respectively. The P&R pathways for DORDs and DRCDs were pharmacoeconomic evaluation waivers (21.7% and 52.6%), weighted average price (52.2% and 13.2%), and risk-sharing agreement (30.4% and 81.6%). CONCLUSION: The copayment reduction system may act as a driver and also barrier for the reimbursement of ODs. To expand treatment accessibility to ODs, it is necessary to consistently grants benefits in all processes from OD designation to market access.

Micro Bio Processor Development Kit for Wireless Neural Implants.

Micro Bio Processor version 1.5 (MBPv15) Development Kit is specially engineered to support various function-alities of implantable devices such as bio-signal sensing, neural stimulation, and dual-band wireless connectivity & charging. It provides a convenient way to evaluate the MBPv15 chip solution as a system component by a modular design of hardware and software. As a result, MBPv15 chip solution enables to develop wireless neural implants in a mm-scale form factor with ultra-low power consumption by achieving 1.6 mW for neural spike detection and 9.8 mW for neural stimulation, respectively.

Evaluation of non-thermal plasma-induced anticancer effects on human colon cancer cells.

Non-thermal atmospheric-pressure plasma has been introduced in various applications such as sterilization, wound healing, blood coagulation, and other biomedical applications. The most attractive application of non-thermal atmospheric-pressure plasma is in cancer treatment, where the plasma is used to produce reactive oxygen species (ROS) to facilitate cell apoptosis. We investigate the effects of different durations of exposure to dielectric-barrier discharge (DBD) plasma on colon cancer cells using measurement of cell viability and ROS levels, western blot, immunocytochemistry, and Raman spectroscopy. Our results suggest that different kinds of plasma-treated cells can be differentiated from control cells using the Raman data.

Piperlongumine induces cell death through ROS-mediated CHOP activation and potentiates TRAIL-induced cell death in breast cancer cells.

PURPOSE: Piperlongumine (PL) has been shown to selectively induce apoptotic cell death in cancer cells via reactive oxygen species (ROS) accumulation. In this study, we characterized a molecular mechanism for PL-induced cell death. METHODS: Cell viability and cell death were assessed by MTT assay and Annexin V-FITC/PI staining, respectively. ROS generation was measured using the H2DCFDA. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein expression were analyzed by RT-PCR and Western blot analysis, respectively. RESULTS: We found that PL promotes C/EBP homologous protein (CHOP) induction, which leads to the up-regulation of its targets Bim and DR5. Pretreatment with the ROS scavenger N-acetyl-cysteine abolishes the PL-induced up-regulation of CHOP and its target genes, suggesting an essential role for ROS in PL-induced CHOP activation. The down-regulation of CHOP or Bim with siRNA efficiently attenuates PL-induced cell death, suggesting a critical role for CHOP in this cell death. Furthermore, PL potentiates TRAIL-induced cytotoxicity in breast cancer cells by upregulating DR5, as DR5 knockdown abolished the sensitizing effect of PL on TRAIL responses. CONCLUSIONS: Overall, our data suggest a new mechanism for the PL-induced cell death in which ROS mediates CHOP activation, and combination treatment with PL and TRAIL could be a potential strategy for breast cancer therapy.

Inhibition of vacuolar H+ ATPase enhances sensitivity to tamoxifen via up-regulation of CHOP in breast cancer cells.

Resistance of estrogen receptor-positive breast cancer cells to tamoxifen represents a major barrier to the successful treatment of breast cancer. In the present study, we found that vacuolar H+ ATPase (vATPase) inhibitors, bafilomycin A1 and concanamycin A, sensitize tamoxifen-induced cell death. siRNA targeting ATP6V0C, a 16-kDa hydrophobic proteolipid subunit of vATPase that plays a central role in H+ transport, markedly increased cell death induced by tamoxifen. Interestingly, bafilomycin A1 induced up-regulation of DR4/DR5 and CHOP. Knock-down of CHOP by siRNA suppressed the cell death induced by bafilomycin A1 and tamoxifen, suggesting that bafilomycin A1-mediated CHOP activation sensitizes to tamoxifen. In addition, we found that bafilomycin A1 enhances TRAIL-induced cell death in breast cancer cells. Furthermore, we showed that combination of vATPase inhibitors with tamoxifen also effectively induced cell death in HER2- and ERα-overexpressing breast cancer cells. Overall, our results demonstrate that inhibition of vATPase can potentiate the apoptotic effects of tamoxifen through up-regulation of CHOP.

Sulindac and its metabolites inhibit invasion of glioblastoma cells via down-regulation of Akt/PKB and MMP-2.

Non-steroidal anti-inflammatory drug (NSAID), sulindac has chemopreventive and anti-tumorigenic properties, however, the molecular mechanism of this inhibitory action has not been clearly defined. The Akt/protein kinase B, serine/threonine kinase is well known as an important mediator of many cell survival signaling pathways. In the present study, we demonstrate that down-regulation of Akt is a major effect of anti-invasiveness property of sulindac and its metabolites in glioblastoma cells. Myristoylated Akt (MyrAkt) transfected U87MG glioblastoma cells showed increase invasiveness, whereas DN-Akt transfected cells showed decrease invasiveness indicating that Akt potently promoted glioblastoma cell invasion. MMP-2 promoter and enzyme activity were up-regulated in Akt kinase activity dependent manner. Sulindac and its metabolites down-regulated Akt phosphorylation, inhibited MMP-2 production, and significantly inhibited invasiveness of human glioblastoma cells. In addition, sulindac and LY294002, a selective inhibitor of phosphoinositide 3-kinase (PI3K), synergistically inhibited the invasion of glioblastoma cells. Furthermore, only celecoxib showed Akt phosphorylation reduction and an anti-invasivness in glioblastoma cells, whereas aspirin, ketoprofen, ketorolac, and naproxen did not. In conclusion, our results provide evidence that down-regulation of Akt pathway and MMP-2 may be one of the mechanisms by which sulindac and its metabolites inhibit glioblastoma cell invasion.