Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Small change for big improvement in the preparation of the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir.

In this study, the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N 1-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N 1, N 3-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs.

Small change for big improvement in the preparation of the key intermediate N1, N3-disubstituted 1,3,5-triazone of ensitrelvir† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2ra07844a

In this study, the key intermediate N1, N3-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N1-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N1, N3-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs. A four-step telescoped strategy for synthesis of the key intermediate of ensitrelvir, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was developed.

Optimal Decision of Dynamic Bed Allocation and Patient Admission with Buffer Wards During an Epidemic

To effectively prevent patients from nosocomial cross-infection and secondary infections, buffer wards for screening infectious patients who cannot be detected due to the incubation period are established in public hospitals in addition to isolation wards and general wards. In this paper, we consider two control mechanisms for three types of wards and patients: one is the dynamic bed allocation to balance the resource utilization among isolation, buffer, and general wards;the other is to effectively control the admission of arriving patients according to the evolution process of the epidemic to reduce mortality for COVID-19, emergency, and elective patients. Taking the COVID-19 pandemic as an example, we first develop a mixed-integer programming (MIP) model to study the joint optimization problem for dynamic bed allocation and patient admission control. Then, we propose a biogeography-based optimization for dynamic bed and patient admission (BBO-DBPA) algorithm to obtain the optimal decision scheme. Furthermore, some numerical experiments are presented to discuss the optimal decision scheme and provide some sensitivity analysis. Finally, the performance of the proposed optimal policy is discussed in comparison with the other different benchmark policies. The results show that adopting the dynamic bed allocation and admission control policy could significantly reduce the total operating cost during an epidemic. The findings can give some decision support for hospital managers in avoiding nosocomial cross-infection, improving bed utilization, and overall patient survival during an epidemic.

Efficacy and safety of Qi and Blood Tonic Chinese Medicines in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) is a sudden public event affecting all human beings, with the rapid transmission, extensive groups affected, many complications, and high mortality. Traditional Chinese Medicine has a long history of preventing and treating infectious diseases, and numerous studies have shown that Traditional Chinese Medicine, especially herbal medicine, has a positive effect on the prevention, treatment, and post-healing recovery of this COVID-19, and herbal medicines to supplement qi and blood often occupy a certain proportion of it. However, there is no relevant meta-analysis to date. Therefore, this study aims to evaluate the efficacy and safety of qi and blood tonic herbal medicines in the treatment of COVID-19 through Systematic Review and meta-analysis to provide a reference basis for widespread clinical application. METHODS: We will search from the following databases for the period from the time of database construction to March 1st, 2023. The English databases include: PubMed, MEDLINE, EMBASE, Cochrane library, WOS, Google Scholar, and CENTRAL; The Chinese databases include: China National Knowledge Infrastructure, China Biomedical Literature Database, Technology Journal Database, and Wanfang. Randomized controlled trials in English or Chinese that include Chinese herbal medicines for tonifying Qi and Blood in the treatment of patients with COVID-19 will be included. Data were independently screened and collected by 2 investigators. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.3 software was used for the meta-analysis of the data. Primary outcome indicators included cure, mortality, and exacerbation rates (change in disease severity category, patient admission to ICU, etc.). Secondary outcome indicators included recovery rate or duration of major symptoms (e.g., fever, cough, fatigue, and weakness, etc.), rate or duration of nucleic acid conversion for severe acute respiratory syndrome coronavirus-2, improvement or recovery of chest CT performance, length of hospital stay, and other adverse events. RESULTS: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P guidelines to ensure clarity and completeness of reporting in all phases of the systematic review. CONCLUSION: This study will provide evidence regarding the efficacy and safety of Qi and Blood Tonic Chinese Medicines for the treatment of COVID-19. PROSPERO REGISTRATION NUMBER: CRD42022361822 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361822).

Integration of a hybrid scan approach and in-house high-resolution MS2 spectral database for charactering the multicomponents of Xuebijing Injection

Xuebijing (XBJ) Injection is a reputable patent Chinese medicine widely used to cure sepsis, among the Chinese ″Three Medicines and Three Prescriptions″ solution to fight against COVID-19. We were aimed to achieve the comprehensive multicomponent characterization from the single drugs to traditional Chinese medicine (TCM) formula, by integrating powerful data acquisition and the in-house MS2 spectral database searching. By ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS), a hybrid scan approach (HDMSE-HDDDA) was developed, while the HDMSE data for five component drugs and 56 reference compounds were acquired and processed to establish an in-house MS2 spectral database of XBJ. Good resolution of the XBJ components was accomplished on a Zorbax Eclipse Plus C18 column within 24 min, while a fit-for-purpose HDMSE-HDDDA approach was elaborated in two ionization modes for enhanced MS2 data acquisition. XBJ MS2 spectral library was thus established on the UNIFITM platform involving rich structure-related information for the chemicals from five component drugs. We could identify or tentatively characterize 294 components from XBJ, involving 81 flavonoids, 51 terpenoids, 42 phthalides, 40 organic acids, 13 phenylpropanoids, seven phenanthrenequinones, six alkaloids, and 54 others. In contrast to the application of conventional MS1 library, this newly established strategy could demonstrate superiority in the accuracy of identification results and the characterization of isomers, due to the more restricted filtering/matching criteria. Conclusively, the integration of the HDMSE-HDDDA hybrid scan approach and the in-house MS2 spectral database can favor the efficient and more reliable multicomponent characterization from single drugs to the TCM formula.

Statistical Approach to Estimating Audience from MAC-Randomized WiFi Probe Requests.

In the past few years, the ability of wireless network operators to monitor audience using control frames emitted by client devices has been compromised, both by legislation treating client MAC addresses as private information and by the difficulty of distinguishing genuine client frames from those arising from the Internet of Things or from certain enhanced services. Here, a deterministic model, based on characteristics of human activity and on seasonal trends, is used to reveal underlying client statistics in raw MAC-randomized WiFi Probe Request data. The method proposes a candidate conversion factor, X, between probe request counts and the client population, which offers plausible predictions on real-world datasets.

Clinical characteristics of patients with confirmed and asymptomatic SARS-CoV-2 infection in China.

OBJECTIVE: To examine the clinical characteristics of patients with asymptomatic novel coronavirus disease 2019 (COVID-19) and compare them with those of patients with mild disease. DESIGN: A retrospective cohort study. SETTING: Multiple medical centers in Wuhan, Hubei, China. PARTICIPANTS: A total of 3,263 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between February 4, 2020, and April 15, 2020. MAIN OUTCOME MEASURES: Patient demographic characteristics, medical history, vital signs, and laboratory and chest computed tomography (CT) findings. RESULTS: A total of 3,173 and 90 patients with mild and moderate, and asymptomatic COVID-19, respectively, were included. A total of 575 (18.2%) symptomatic patients and 4 (4.4%) asymptomatic patients developed the severe illness. All asymptomatic patients recovered; no deaths were observed in this group. The median duration of viral shedding in asymptomatic patients was 17 (interquartile range, 9.25-25) days. Patients with higher levels of ultrasensitive C-reactive protein (odds ratio [OR] = 1.025, 95% confidence interval [CI], 1.01-1.04), lower red blood cell volume distribution width (OR = 0.68, 95% CI 0.51-0.88), lower creatine kinase Isoenzyme(0.94, 0.89-0.98) levels, or lower lesion ratio (OR = 0.01, 95% CI 0.00-0.33) at admission were more likely than their counterparts to have asymptomatic disease. CONCLUSIONS: Patients with younger ages and fewer comorbidities are more likely to be asymptomatic. Asymptomatic patients had similar laboratory characteristics and longer virus shedding time than symptomatic patients; screen and isolation during their infection were helpful to reduce the risk of SARS-CoV-2 transmission.

Elevated Fasting Blood Glucose Levels Are Associated with Worse Clinical Outcomes in COVID-19 Patients Than in Pneumonia Patients with Bacterial Infections.

AIMS: We investigate how fasting blood glucose (FBG) levels affect the clinical severity in coronavirus disease 2019 (COVID-19) patients, pneumonia patients with sole bacterial infection, and pneumonia patients with concurrent bacterial and fungal infections. METHODS: We enrolled 2761 COVID-19 patients, 1686 pneumonia patients with bacterial infections, and 2035 pneumonia patients with concurrent infections. We used multivariate logistic regression analysis to assess the associations between FBG levels and clinical severity. RESULTS: FBG levels in COVID-19 patients were significantly higher than in other pneumonia patients during hospitalisation and at discharge (all p < 0.05). Among COVID-19 patients, the odds ratios of acute respiratory distress syndrome (ARDS), respiratory failure (RF), acute hepatitis/liver failure (AH/LF), length of stay, and intensive care unit (ICU) admission were 12.80 (95% CI, 4.80-37.96), 5.72 (2.95-11.06), 2.60 (1.20-5.32), 1.42 (1.26-1.59), and 5.16 (3.26-8.17) times higher in the FBG ≥7.0 mmol/L group than in FBG < 6.1 mmol/L group, respectively. The odds ratios of RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with sole bacterial infection (3.70 [2.21-6.29]; 1.56 [1.17-2.07]; 0.98 [0.88-1.11]; 2.06 [1.26-3.36], respectively). The odds ratios of ARDS, RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with concurrent infections (3.04 [0.36-6.41]; 2.31 [1.76-3.05]; 1.21 [0.97-1.52]; 1.02 [0.93-1.13]; 1.72 [1.19-2.50], respectively). Among COVID-19 patients, the incidence rate of ICU admission on day 21 in the FBG ≥ 7.0 mmol/L group was six times higher than in the FBG < 6.1 mmol/L group (12.30% vs. 2.21%, p < 0.001). Among other pneumonia patients, the incidence rate of ICU admission on day 21 was only two times higher. CONCLUSIONS: Elevated FBG levels at admission predict subsequent clinical severity in all pneumonia patients regardless of the underlying pathogens, but COVID-19 patients are more sensitive to FBG levels, and suffer more severe clinical complications than other pneumonia patients.

Tourists' perceived restorative qualities and post-visit behavioral intention:the mechanism and boundary condition

Studies have shown that contacting with beautiful natural environments improves people's mood and reduces pressure. Environments that facilitate physical and psychological recovery are called restorative environments. Compared with other types of environments, natural sightseeing resorts have the most prominent restorative value, and have attracted the attention of numerous scholars. Tourists' perceived restorative qualities have gradually become a frontier of environmental psychology and tourism studies. However, studies of tourists' perceived restorative qualities are still in their infancy, with limited results regarding various aspects. For example, the development of a tourist restorative perception scale, and the antecedent factors underlying tourists' perceived restorative qualities. Few studies can be found investigating the relationship between tourists' perceived restorative qualities and their post-visit behavioral intention. Post-visit behavioral intention is of great significance in terms of guiding the management and marketing of tourist destinations. The COVID-19 pandemic has led to a sharp decline in the willingness of potential tourists to travel. As consumption by tourists shifts toward the pursuit of greenness and health during the continuation of the epidenic, further improving their satisfaction, stimulating word-ofmouth promotion, and strengthening tourist loyalty through physical and mental recovery experience to enable tourist destinations to enhance their competitive advantage, then to revitalize, has become an issue worthy of investigation. By maintaining close contact with destination environment, tourists can effectively enhance their physical and mental functions, produce a sense of satisfaction and increase positive behavioral intention. Thus, it is important to explore the mechanism underlying tourists' perceived restorative qualities to aid product innovation and marketing promotion, and promote the sustainable development of tourist destinations. On the basis of previous studies, we used attention restoration theory to analyze the impact of tourists' perceived restorative qualities. On the basis of the Mehrabian-Rusell framework, we developed a theoretical integrated model including four constructs:Tourists' perceived restorative qualities, tourist satisfaction, post-visit behavioral intention and tourist involvement. The model was tested using structural equation modeling. All constructs were measured using selfreported, multiple-item scales adopted from previous studies. Data were collected from Kanas, a well known nature-based tourist destination located in Altay, China. The questionnaires were distributed by a group of five people on 1-7 August 2019. A total of 600 questionnaires were distributed, and 547 completed questionnaires were returned. The results were as follows:(1) Tourists' functional perceived restorative qualities(coherence, novelty) directly and positively affect their emotional perceived restorative qualities(fascination, compatibility, escape);(2) Novelty and escape are key factors affecting post-visit behavioral intention, and fascination and compatibility affect post-visit behavioral intention through satisfaction. Furthermore, novelty, compatibility and satisfaction have a multiple chain-mediating effect on the relationship between coherence and post-visit behavioral intention, while compatibility and satisfaction have a multiple chain-mediating effect on the relationship between novelty and post-visit behavioral intention;(3) The influence of fascination and compatibility on satisfaction is positively regulated by tourist involvement;and(4) The effect of tourists' perceived restorative qualities on their post-visit behavioral intention exhibited a three-stage"environmental stimuli perception-emotion-intention"transmission mechanism.In this study, we analyzes the benefits of tourists' perceived restorative qualities, which provides important references for tourism destination managers in relation to environmental optimization, marketing and brand building. T

High Fasting Blood Glucose Level With Unknown Prior History of Diabetes Is Associated With High Risk of Severe Adverse COVID-19 Outcome.

Background: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications. Methods: We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients. Results: COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3. Conclusion: Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.

Elevated glucose level leads to rapid COVID-19 progression and high fatality.

OBJECTIVES: We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. METHODS: We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. RESULTS: The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. CONCLUSIONS: Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.