Clinical Profile of COVID-19 Patients Admitted at a Private Hospital During Three Surges in Mandalay, Myanmar.

Introduction During the coronavirus disease 2019 (COVID-19) pandemic, private hospitals in Mandalay started to manage COVID-19 infections according to national treatment guidelines since February 2021. Variations of clinical characteristics and their outcomes in different surges could be evaluated in the private hospital. This study aimed to assess the clinical profile and outcomes of COVID-19 patients admitted at a private hospital during three surges in Mandalay. Methods This study is a retrospective record review of the case series of COVID-19 patients admitted at City Hospital, Mandalay. The study was conducted from January to December 2022. All of the hospital records of COVID-19 patients admitted during the second wave from February 2020 to 26 May 2021, the third wave from 27 May 2021 to 27 January 2022, and the fourth wave from 28 January to April 2022 were included in the study. Results A total of 1606 admitted cases were included in the study. The mean with standard deviation (SD) of age was 55.7±18.5, and males were 778 (48.4%). The mean duration of hospital stay in days was 10.8±5.94, 10.6±6.11, and 7.3±2.88 in second, third, and fourth waves, respectively. The mean duration of hospital stay was shortened in the fourth wave. Comorbid conditions with hypertension and/or diabetes diseases were mostly observed in three waves of COVID-19 infection. Fever was the most presented symptom in three waves. Cough, sore throat, and rhinorrhea were observed more in the fourth wave compared with previous waves. Complication with pneumonia (71.3%), liver dysfunction (21.0%), acute respiratory distress syndrome (10.0%), thrombocytopenia (6.2%), acute kidney injury (5.5%), bleeding (3.9%), and pulmonary embolism (2.9%) were investigated. Antiviral treatment such as remdesivir or molnupiravir was used more in the patients of third and fourth waves than those of the second wave. Oxygen therapy (59.9%), prone position (35.5%), non-invasive ventilation (9.5%), invasive ventilation (0.5%), inotropes (4.6%), and renal replacement therapy (1.1%) were recorded in serious cases. Only 7.9% and 9.4% died in the hospital in second and third waves. No mortality was observed in the fourth wave. Conclusions The study recommended that COVID-19 patients with comorbid conditions of hypertension or diabetes and ages 65 and older should be taken with intensive care support at the hospital. This study also concluded that a private hospital in Mandalay could tackle with COVID-19 severe cases in line with national treatment guidelines since the second wave and could provide better management in the fourth wave. Antiviral treatment should be used in severe COVID-19 cases for further emergency management. In conclusion, private hospital involvement in the COVID-19 pandemic is supportive of the healthcare provision in Myanmar in an emergency situation.

Clinicopathological significance of calreticulin in breast invasive ductal carcinoma.

Calreticulin is a chaperone protein located in the lumen of the endoplasmic reticulum. The association of calreticulin with pathological conditions such as autoimmune disorders and certain types of cancer have been reported. However, little is known about its role in the pathogenesis of breast cancer. The aim of this study was to determine the expression of calreticulin in vitro and correlate its expression levels in breast cancer tissue samples with clinicopathological parameters. Calreticulin expression was evaluated in MCF-7 and MDA-MB-231 breast cancer cells by real-time RT-PCR, Western blot, immunohistochemistry, and immunofluorescence staining. Patient tissue microarrays were constructed from 228 breast cancer specimens for immunohistochemical analysis. The in vitro study showed a higher calreticulin expression in more aggressive MDA-MB-231 cells as compared with MCF-7 cells at both mRNA and protein levels. In all, 227 out of 228 breast cancer samples exhibited calreticulin staining in at least 5% of the cancer cells. Calreticulin immunostaining was observed to be localized to the cytoplasm of the cancer cells. Regression analysis of calreticulin immunostaining in the tissue microarrays revealed that its expression was positively correlated to logarithm of (log) tumor size (P=0.046) and development of distant metastasis (P=0.017). Multivariate analysis confirmed calreticulin expression as an independent predictor of log tumor size and occurrence of distant metastasis. The data suggest that calreticulin expression is associated with more advanced tumors and is a potential prognostic biomarker.

Heat shock proteins as novel therapeutic targets in cancer.

Heat shock proteins (HSPs) are evolutionarily conserved molecules synthesised by cells exposed to sub-lethal stresses. Acting as molecular chaperones, HSPs protect cells from environmental stress damage by assisting in proper folding and stabilisation of proteins. In addition, they help to sequester severely damaged proteins for degradation. Owing to the nature of their function, HSPs are often found to be overexpressed in a wide range of cancers. Members of the HSP family have been implicated in cancer growth as promoting tumour cell proliferation as well as inhibiting cellular death pathways. In recent years, several HSP90 client proteins have been validated as clinically important therapeutic targets for treatment of cancer, and inhibitors of HSP90 have emerged as potentially beneficial anticancer agents. This review explores the involvement of HSPs in cancer and the development of several anticancer agents with promising therapeutic applications.

Factors controlling vegetation fires in protected and non-protected areas of myanmar.

Fire is an important disturbance agent in Myanmar impacting several ecosystems. In this study, we quantify the factors impacting vegetation fires in protected and non-protected areas of Myanmar. Satellite datasets in conjunction with biophysical and anthropogenic factors were used in a spatial framework to map the causative factors of fires. Specifically, we used the frequency ratio method to assess the contribution of each causative factor to overall fire susceptibility at a 1km scale. Results suggested the mean fire density in non-protected areas was two times higher than the protected areas. Fire-land cover partition analysis suggested dominant fire occurrences in the savannas (protected areas) and woody savannas (non-protected areas). The five major fire causative factors in protected areas in descending order include population density, land cover, tree cover percent, travel time from nearest city and temperature. In contrast, the causative factors in non-protected areas were population density, tree cover percent, travel time from nearest city, temperature and elevation. The fire susceptibility analysis showed distinct spatial patterns with central Myanmar as a hot spot of vegetation fires. Results from propensity score matching suggested that forests within protected areas have 11% less fires than non-protected areas. Overall, our results identify important causative factors of fire useful to address broad scale fire risk concerns at a landscape scale in Myanmar.

Downregulation of ER60 protease inhibits cellular proliferation by inducing G1/S arrest in breast cancer cells in vitro.

ER60 protease, a 58-kDa molecular chaperone in the endoplasmic reticulum, is involved in glycoprotein synthesis. ER60 protease has been reported to be differentially expressed in various cancers including breast carcinoma. This study explored the relationship of ER60 protease with cell proliferation in breast cancer in vitro. ER60 protease expression was first determined in a panel of breast cell lines by real-time RT-PCR and Western blot analysis and found to be most abundantly expressed in T47D breast cancer cells. The ER60 protease gene was then successfully knocked down in T47D breast cancer cells using two different sequences of small-interfering RNA. The silencing efficiencies of siER-1 and siER-2 at 48-hr post-transfection were found to be >80% at the mRNA level with concomitant downregulation of the ER60 protease protein by >60% when compared with control T47D breast cancer cells. Downregulation of ER60 protease was also associated with inhibition of cell proliferation when assessed by the AlamarBlue assay. Cell cycle analysis performed on the siER-1- and siER-2-transfected cells, revealed an increase in G1 phase population and a decrease in the S and G2/M phase populations compared with control cells, implicating G1/S cell cycle arrest. It would appear that ER60 protease is involved in breast tumorigenesis and could therefore be a prospective target for cancer therapeutics.

Function of sirtuins in biological tissues.

Sirtuins are protein deacetylases, which are dependent on nicotine adenine dinucleotide. They are phylogenetically conserved from bacteria to humans. Seven sirtuin proteins localized in a wide variety of subcellular locations have been identified in the human genome. The most important known function of sirtuins is their regulation of transcriptional repression, mediated through binding of a complex containing sirtuins and other proteins. Studies have shown that sirtuins have pathophysiological relevance to neurodegeneration, muscle differentiation, inflammation, obesity, and cancer. In addition, sirtuin activity extends the lifespan of several organisms. In this review, we discuss the mode(s) of action of sirtuins, and their biological role(s) in health and disease.