Ribosome biogenesis in disease: new players and therapeutic targets.

The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

The impact of the COVID-19 pandemic on a surgical PICU in China that did not admit COVID-19 patients.

Background: The unprecedented COVID-19 pandemic has been spreading for a long time. However, it is unclear whether the pandemic influenced admission in a surgical pediatric intensive care unit (PICU) that never received COVID-19 patients during the early outbreak in China. Methods: A retrospective study was conducted in a surgical PICU in a tertiary hospital in Chengdu, China. We sought to describe the trend in admission numbers from January 2018 to April 2021. We explored the impact of the COVID-19 outbreak on PICU admission characteristics by including all patients younger than 18 years admitted to the PICU between January 23 and April 8 in 2020 and those admitted in the same time periods in prepandemic years (2018 and 2019) and in 2021. Results: The percentage of patients admitted to the PICU from the Chengdu region increased from 34.2 percent in 2019 to 40.4 percent in 2020, whereas that from other provinces decreased from 11.7 percent in 2019 to 5.8 percent in 2020 (P = 0.012). The median length of stay (LOS) in the PICU was significantly longer in the 2020 cohort (4.0 days) than in the 2019 cohort (2.0 days) (P < 0.001); the median hospital LOS was also significantly longer in the former (12.0 days) than in the latter (8.0 days) (P < 0.001). Hospital outcomes (P = 0.005) and primary diagnosis distributions (P = 0.025) between the 2020 and 2019 cohorts were both statistically significant. Conclusions: In a surgical PICU that never received COVID-19 patients, the onset of the 2020 major outbreak was accompanied by changes in the composition of the regional sources of patients, longer PICU and hospital stays, increased proportions of unauthorized discharges, and changes in the distribution of primary diseases for admission. These findings have yet to be strengthened by additional studies involving similar healthcare backgrounds.

Predicting Risks of a COVID-19 Outbreak by Using Outdoor Air Pollution Indicators and Population Flow with Queuing Theory

COVID-19 has been widespread in all countries since it was first discovered in December 2019. The high infectivity of COVID-19 is primarily transmitted between people via respiratory droplets on contact routes, which makes it more difficult to prevent it. Air quality has been considered to be highly correlated with respiratory diseases. In addition, population movement increases contact routes, which increases the risk of COVID-19 outbreaks. For epidemic prevention, the government's strategies are also one of the factors that affect the risk of outbreaks, including whether it is mandatory to wear masks, stay-at-home orders, or vaccination. Wearing masks can reduce the risk of droplet infection, while stay-at-home orders can reduce contact between people. In this study, the number of COVID-19 confirmed cases and active cases of COVID-19 will be estimated according to the population movement, outdoor air pollution, and vaccination rates. Using the estimated results, the average recovery time will be predicted by Queuing Theory. The predicted average recovery time will be brought into risk analysis to estimate the possible high-risk periods. We compare the estimated high-risk periods with epidemic-prevention measures to provide a reference to evaluate the epidemic prevention plans enforced by relevant government agencies to achieve an improved control measure over the epidemic situation.

A Positive Legacy of Trauma? The Role of Perceived Social Support on Mental Health Among Earthquake Survivors During the COVID-19 Outbreak

Background People with prior experience of severe trauma may be particularly vulnerable in the face of the COVID-19 pandemic. However, little is known about mental health problems among prior trauma survivors during the pandemic outbreak. Methods A total of 362 Wenchuan earthquake survivors were assessed using Patient Health Questionnaire, Generalized Anxiety Disorder Scale, as well as Multidimensional Scale of Perceived Social Support, as part of an online survey between February 3 and 10, 2020. Results Our results showed that 6.6 and 4.7% of the participants experienced depression and anxiety during the COVID-19 outbreak, respectively. Perceived social support was negatively associated with depressive and anxiety symptoms. Earthquake exposure has no direct effect on current depressive and anxiety symptoms, but it would moderate the direct relationship between perceived social support and psychological symptoms. Conclusions Our findings suggested that trauma exposure may lead to salutogenic outcomes. The protective effect of perceived social support on psychological symptoms was greater in people with a higher level of trauma exposure than in a lower one.

COVID-19 Pandemic Analysis for a Country’s Ability to Control the Outbreak Using Little’s Law: Infodemiology Approach

Since the outbreak of the coronavirus disease (COVID-19), all countries across the globe have been trying to control its spread. A country’s ability to control the epidemic depends on how well its health system accommodates COVID-19 patients. This study aimed to assess the ability of different countries to contain the COVID-19 epidemic in real-time with the number of confirmed cases, deaths and recovered cases. Using the dataset provided by the Humanitarian Data Exchange (HDX), we analyzed the spread of the virus from 22 January 2020 to 15 September 2020 and used Little’s Law to predict a country’s ability to control the epidemic. According to the average recovery time curve changes, 16 countries are divided into different categories—Outbreak, Under Control, Second Wave of Outbreak, and Premature Lockdown Lift. The curves of outbreak countries (i.e., U.S., Spain, Netherlands, Serbia, France, Sweden, and Belgium) showed an upward trend representing that their medical systems have been overloaded and are unable to provide effective medical services to patients. On the other hand, after the pandemic-prevention policy was applied, the average recovery time dropped in under control countries (i.e., Iceland, New Zealand, Taiwan, Thailand, and Singapore). Finally, we study the impact of interventions on the average recovery time in some of the countries. The interventions, e.g., lockdown and gathering restrictions, show the effect after 14 days, which is the same as the incubation period of COVID-19. The results show that the average recovery time (T) can be used as an indicator of the ability to control the pandemic.