One new indolocarbazole, 3-hydroxy-K252d (3), together with the recently reported 3-hydroxyholyrine A (1) and 3′-N-acetyl-3-hydroxyholyrine A (2), were obtained by feeding a culture of the marine-derived Streptomyces strain OUCMDZ-3118 with 5-hydroxy-l-tryptophan. Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 potently induced apoptosis of gastric cancer cells by inhibiting topoisomerase IIα enzyme activity and reducing the expression of antiapoptosis protein level. Compound 3 displayed moderate cytotoxicity against the A549 and MCF-7 cell lines with IC50 values of 1.2 ± 0.05 μM, 1.6 ± 0.09 μM, respectively.

Background. Metal artisans have been using lead and mercury in their settings for centuries. Exposure to these toxic heavy metals causes adverse health effects. We assessed the occupational exposure of metal artisans and their high-risk household contacts at Thimphu, Bhutan. Methods. A cross-sectional study in which 134 metal artisan center employees and 48 high-risk household contacts were tested for blood lead and mercury levels. Sociodemographic data, occupational exposure risk factors, and clinical syndrome related to lead and mercury exposure were further obtained and analyzed using EpiInfo 7.0. Results. The mean age of the metal artisan center employees was 36.02 ± 10.3. The prevalence of elevated blood lead and mercury level was 38.4% and 51.9%, respectively. Significantly higher prevalence of mercury level was observed among the artisans compared to nonartisans (66.97 vs, 16.0). Among three centers, the goldsmith section of the Department of National Properties had the highest (94.1%). Profession as an artisan, mold designing, performing gold amalgamation, working for >8 hours a day, working for >5 years, and working at home were significant risk factors associated with elevated blood mercury level. Significant association was observed between elevated mercury level and complaints of burning or watery eyes (p=0.001), anxiety, nervousness, irritability, severe shyness (p=0.029), muscle aches (p=0.019), and stomach cramps or pain (p=0.009). Conclusion. The prevalence of elevated blood mercury level is concerning among the artisans. Advocacy, proper usage of personal protective equipment, awareness on chemical safety, and hazard associated with lead and mercury usage are needed to minimize the exposure.

Introduction: The COVID-19 pandemic has stretched into the tiny Himalayan country Bhutan and the first suspected case was seen on 27 th January 2020. There are no reports available in the country till date. Therefore, a descriptive study was conducted to understand the epidemiological characteristics of confirmed COVID-19 cases in Bhutan as of 30 th April 2020. Methods: Data were extracted from the Royal Center for Disease Control COVID-19 information database and analyzed using Epi Info 7.2. Results: A total of 1716 individuals were tested for SARS-CoV-2 infection and seven were confirmed positive using RT-PCR. The median age and incubation period were 20 years and 5 days respectively. The predominant clinical symptoms included loss of smell (71.0%) followed by fever (42.8%) and sore throat (42.8%). Notably, there is no reported local transmission in the country. Conclusion: The robust surveillance system plays a vital role in active case findings in COVID-19 cases. Further efforts should be continually focused on surveillance and testing for the containment of the infection to prevent local transmission.

Thiamine (vitamin B1) deficiency can cause beriberi leading to cardiac involvement or, more commonly, peripheral neuropathy. Common causes of thiamine deficiency are alcohol use, maternal thiamine deficiency, poor dietary diversity, unhygienic food preparation, and unsafe cooking practices. This report presents an analysis of suspected peripheral neuropathy outbreaks recorded at the Royal Centre for Disease Control between 2020 and 2021. The suspected outbreaks were reported from schools and monastic institutes with the main complaints of numbness and swelling of lower limbs. Three of the four events were confirmed due to thiamine deficiency by laboratory analysis. Of 34 samples tested, 27 (79%) had thiamine deficiency, defined as a thiamine diphosphate (ThDP) level <75.0 nmol/L. The mean ThDP level was 56.5 nmol/L. There were no statistically significant differences in the average ThDP level among the patients of different age groups. Given the fact that micronutrient deficiency was established as the cause of the current peripheral neuropathy outbreaks, we recommend that the supply of fortified rice across both government and private institutes in the country be initiated. Holistic approaches should be implemented to reduce the burden of micronutrient deficiencies in the country.