Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the -helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.

Clinical skills in final-year medical students: the relationship between self-reported confidence and direct observation by faculty or residents

<p><b>INTRODUCTION</b>Many students, while performing clinical skills such as medical interviewing/ communication, physical examination, and procedural tasks, have never been observed by faculty members or residents. This study aimed to explore the relationships between final-year medical students' self-reported confidence and the frequency of direct observation by faculty member or resident while conducting these clinical skills.</p><p><b>MATERIALS AND METHODS</b>Medical students at China Medical University in Taiwan participated in the survey. Before graduating, they were asked to answer a questionnaire about (1) their confidence in performing 17 clinical skills including medical interviewing/communication, physical examination, and procedural tasks, and (2) the number of times they had been directly observed by faculty members or residents during student-patient encounters.</p><p><b>RESULTS</b>Many students reported never having been observed by a faculty member while they performed history taking/communication (46% to 84%), physical examination (36% to 42%), or procedural tasks (41% to 81%). It was found that residents had observed the students more frequently than the faculty members. The correlations between self-reported confidence and the corresponded direct observation were small to medium but significant. However, no difference was found between observation by a faculty member and by a resident.</p><p><b>CONCLUSIONS</b>This study confirmed that many medical students have not been directly observed in clinical training; and that those who were observed more often, expressed more self-reported confidence. Some assessment measures, which focus on direct observation and feedback during student-patient encounters, may improve the students' confidence.</p>

Cytochrome P450c17alpha (CYP17) gene polymorphism is not associated with leiomyoma susceptibility

Estrogen plays a role in the pathogenesis of leiomyoma. The CYP17 gene codes for the cytochrome P450c17alpha enzyme, which is involved in the biosynthesis of estrogen. Our aim was to investigate if CYP17 polymorphism could be a useful marker to predict the susceptibility to leiomyoma. Our sample of female subjects was divided into two groups: (1) with leiomyoma (n = 159); (2) without leiomyoma (n = 128). A 169-bp fragment encompassing the A1/A2 polymorphic site of the CYP17 gene was amplified by polymerase chain reaction (PCR), restricted by enzyme MspA1I and electrophored on agarose gel. Genotypes and allelic frequencies for this polymorphism in both groups were compared. There was no significant difference between the two groups regarding the distribution of the CYP17 gene polymorphism frequencies. The A1 homozygote/heterozygote/A2 homozygote proportions for CYP17 in both groups were: (1) 17.0/46.5/36.5 percent, and (2) 17.2/45.3/37.5 percent. The proportions for alleles A1 and A2 were also comparable in the two groups. A1 and A2 allele frequencies were: 7 percent (40.3/59) in group 1, and 2 percent (39.8/60) in group 2. No significant association was observed between the risk of leiomyoma and polymorphisms of the CYP 17 gene. So, CYP17 gene polymorphism does not appear to be a useful marker for the prediction of leiomyoma susceptibility