Background The coronavirus disease 2019 (COVID-19) pandemic is a major public health concern. Accurate and rapid diagnosis of COVID-19 is critical for disease control. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a nucleic acid amplification assay similar to reverse transcription-polymerase chain reaction (RT-PCR), the former being a simple, low cost, and rapid method. Objectives This study aimed to compare the RT-LAMP assay with RT-PCR using the Loopamp TM SARS-CoV-2 Detection Kit. Study Design One hundred and fifty-one nasopharyngeal swab and 88 sputum samples obtained from individuals with suspected or confirmed COVID-19 were examined. Results RT-LAMP had high specificity (98.5% (95% CI: 96.9–100%)), sensitivity (87.0% (95% CI: 82.8–91.3%)), positive predictive value (97.9% (95% CI: 96.1–99.7%)), negative predictive value (90.2% (95% CI: 86.4–94.0%)), and concordance rate (93.3% (95% CI: 90.1–96.5%)). Nasopharyngeal and sputum samples positive in RT-LAMP contained as few as 10.2 and 23.4 copies per 10 μL, respectively. RT-LAMP showed similar performance to RT-PCR for samples with cycle threshold value below 36. Conclusions These results indicate that RT-LAMP is a highly reliable and at least equivalent to RT-PCR in utility, and potentially applicable in settings that are more diverse as a point-of-care tool.

The bacterial mechanosensitive channel, MscL, is activated by membrane tension, acting as a safety valve to prevent cell lysis against hypotonic challenge. It has been established that its activation threshold decreases with membrane thickness, while the underlying mechanism remains to be solved. We performed all-atom molecular dynamics (MD) simulations for the initial opening process of MscL embedded in four different types of lipid bilayers with different thicknesses: 1,2-dilauroyl- sn-glycero-3-phosphocholine (DLPC)), 1,2-dimyristoyl-glycero-3-phosphorylcholine (DMPC), 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl- sn-glycero-3-phosphocholine (DSPC). In response to membrane stretching, channel opening occurred only in the thinner membranes (DLPC and DMPC) in a thickness-dependent way. We found that the MscL opening was governed by the rate and degree of membrane thinning and that the channel opening was tightly associated with the tilting of transmembrane (TM) helices of MscL toward the membrane plane. Upon membrane stretching, the order parameter of acyl chains of thinner membranes (DLPC and DMPC) became smaller, whereas other thicker membranes (DPPC and DSPC) showed interdigitation with little changes in the order parameter. The decreased order parameter contributed much more to membrane thinning than did interdigitation. We conclude that the membrane-thickness-dependent MscL opening mainly arises from structural changes in MscL to match the altered membrane thickness by stretching.

Background: Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear. Methods and Results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes. Conclusions: We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.

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