Simulation of COVID-19 Epidemic from Potential Viral Loads in Saudi Arabian Wastewater Treatment Plants (preprint)

SARS-CoV-2 is a contagious respiratory virus that has been discovered in sewage, human waste, and wastewater treatment facilities. Wastewater surveillance has been considered one of the lowest-cost means of testing for tracking the COVID-19 outbreak in communities. This paper highlights the dynamics of the virus's infection, persistence, and occurrence in wastewater treatment plants. Our aim is to develop and implement a mathematical model to infer the epidemic dynamics from the possible density of SARS-CoV-2 viral load in wastewater. We present a long-normal model and fractional order of susceptible-exposed-infected-recovery (SEIR) epidemic model for predicting the spread of the COVID-19 disease from the wastewater data. We study the dynamic properties of the fractional order SEIR model with respect to the fractional ordered values. The model is used to comprehend how the coronavirus spreads through wastewater treatment plants in Saudi Arabia. Our modeling approach can help with wastewater surveillance for early prediction and cost-effective monitoring of the epidemic outbreak in a situation of low testing capacity.

In Silico and In Vitro Evaluation of Some Amidine Derivatives as Hit Compounds towards Development of Inhibitors against Coronavirus Diseases.

Coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and influenza A virus, require the host proteases to mediate viral entry into cells. Rather than targeting the continuously mutating viral proteins, targeting the conserved host-based entry mechanism could offer advantages. Nafamostat and camostat were discovered as covalent inhibitors of TMPRSS2 protease involved in viral entry. To circumvent their limitations, a reversible inhibitor might be required. Considering nafamostat structure and using pentamidine as a starting point, a small set of structurally diverse rigid analogues were designed and evaluated in silico to guide selection of compounds to be prepared for biological evaluation. Based on the results of in silico study, six compounds were prepared and evaluated in vitro. At the enzyme level, compounds 10-12 triggered potential TMPRSS2 inhibition with low micromolar IC50 concentrations, but they were less effective in cellular assays. Meanwhile, compound 14 did not trigger potential TMPRSS2 inhibition at the enzyme level, but it showed potential cellular activity regarding inhibition of membrane fusion with a low micromolar IC50 value of 10.87 µM, suggesting its action could be mediated by another molecular target. Furthermore, in vitro evaluation showed that compound 14 inhibited pseudovirus entry as well as thrombin and factor Xa. Together, this study presents compound 14 as a hit compound that might serve as a starting point for developing potential viral entry inhibitors with possible application against coronaviruses.

Determinants of financial stability and risk transmission in dual financial system: Evidence from the COVID pandemic

Existing literature on spillovers and connectedness between Islamic and conventional financial markets overlooked the fundamental role played by money markets in volatility spillovers and risk transmission across markets. That being so, this paper aims at investigating the dynamic co-movements and volatility spillovers across Islamic and conventional financial markets in a dual financial system over the period from January 3, 2007 to June 30, 2021. To this end, the DECO-GJR-GARCH model and the volatility spillover approach were applied. Furthermore, the ARDL model was utilised to explore the key determinants of co-movements and risk transmission across Islamic and conventional financial markets. This not only allowed us to study the interconnectedness and volatility spillovers between financial sectors under different market conditions but also enabled us to highlight the key role played by the money markets. Empirical results show that markets have significant responses to any new relevant information. While both conventional stock and money market are the main transmitters of shocks to other markets, the Islamic money market is a net recipient. Furthermore, the volatility spillovers across conventional and Islamic financial markets became stronger during the COVID-19 epidemic. The study also finds that global uncertainties have a significant and negative impact on the dynamic co-movements, but not on volatility connectedness among the underlying markets. These findings have important implications for many stakeholders including portfolio managers, investors, and policymakers in terms of diversifying their portfolios and enhancement of financial stability during times of black swan events and negative shocks such as the COVID-19 pandemic.

Paracetamol Overdose Induces Acute Liver Injury accompanied by oxidative stress and inflammation

The concept of paracetamol as a safe drug has become very misleading as this has led to a high rate of paracetamol toxicity. Hepatotoxicity and liver failure have been reported even with doses just more than the maximum therapeutic dose, which was obviously noticed in the (COVID-19) pandemic. Oxidative stress plays an important role in paracetamol hepatotoxicity. The current study investigates the mechanism of action through which paracetamol induces hepatotoxicity and implements an alarming sign for the unsupervised use of paracetamol. Twenty albino rats were equally divided into a normal control group and paracetamol treated group where rats received paracetamol at a dose of 2g/kg b.wt once orally for 24 hours. Oral administration of paracetamol resulted in a significant elevation of liver enzymes in serum such as glutamate pyruvate transaminase and glutamate oxaloacetate transaminase when compared with the results of the control group. In terms of oxidative stress biomarkers, the group that received an overdose of paracetamol showed a significant increase in the tissue level of 4-Hydroxynonenal accompanied by a significant decrease in the activity of the anti-oxidant markers Paraoxonase and Catalase. Histopathological examination revealed focal necrosis in the hepatocytes, Centri-lobular necrobiotic changes, and dilated congested portal vein. Immunohistochemical investigation for the Nuclear factor-kappa B showed strong positive expression in the nuclei of the hepatocytes of rats that received an overdose of paracetamol. Our study suggests that an overdose of paracetamol could attenuate the endogenous antioxidant defense mechanisms and augment the hepatic tissue inflammation;both factors may contribute to the observed increase in apoptosis-related signaling and cell death. ©2023 National Information and Documentation Center (NIDOC).

Imperial Prostate-4 Comparative Healthcare Research Outcomes of Novel Surgery in Prostate Cancer (Ip4-Chronos): Early Feasibility, Safety and Functional Outcomes from a Pilot Rct

INTRODUCTION AND OBJECTIVE: Randomised comparative outcomes are unavailable for focal therapy in localised prostate cancer. IP4 CHRONOS is an RCT aimed to optimise recruitment of patients dependent upon clinician and patient equipoise. METHOD(S): Patients with clinically significant localised prostate cancer could opt for IP4-CHRONOS-A or IP4-CHRONOS-B. IP4- CHRONOS-A randomised patients 1:1 between focal therapy(HIFU or cryotherapy) versus radical therapy(radiation or prostatectomy). Using a multi-arm-multistage(MAMS)design, IP4-CHRONOS-B randomised between focal alone(FTA) and focal combined with neoadjuvant medication (12 weeks of finasteride [FTF] or bicalutamide [FTB]). We report the pilot phase outcomes on feasibility of randomisation, early safety outcomes relative to treatment and genito-urinary functional outcomes following over 12 months treatment in IP4-CHRONOS-B. IP4-CHRONOS had ethics committee approval and was registered(ISRCTN17796995). RESULT(S): Following COVID-19 adjustments, IP4-CHRONOSA did not meet its feasibility target. Having randomised 36 patients via10 sites with a recruitment rate (95% CI) of 18% (13-23) & randomisation rate of 97%(86-100). IP4-CHRONOS-B did meet its target, randomising 64 patients across 7 sites with a recruitment rate of 43% (35-52) &randomisation rate of 100%(94-100). The only patients to withdraw were randomised to the radical arm of IP4-CHRONOS-A(4 [22%]) All patients in IP4-CHRONOS-B were compliant with neoadjuvant treatment.Only 1 patient reported CTCAE V4.0 grade>=3 adverse event(AE) in IP4-CHRONOS-A following radical treatment, another patient in each arm reported a serious adverse event(SAE) following treatment. 1 &3 patients reported an AE &SAE following FTB. 2 and 3 patients reported an AE &SAE following FTA. No patients reported any AE or SAE event following FTF. Figure 1 demonstrates generally well preserved genito-urinary function following focal treatment+/-neoadjuvant treatment. CONCLUSION(S): IP4-CHRONOS evaluated patient and physician equipoise regarding focal therapy. Traditional randomisation was not feasible due to strong patient preferences, while a MAMS RCT investigating the role of neoadjuvant agents combined with focal therapy was.

Synchronous spectrofluorimetric determination of favipiravir and aspirin at the nano-gram scale in spiked human plasma; greenness evaluation.

Favipiravir and aspirin are co-administered during COVID-19 treatment to prevent venous thromboembolism. For the first time, a spectrofluorometric method has been developed for the simultaneous analysis of favipiravir and aspirin in plasma matrix at nano-gram detection limits. The native fluorescence spectra of favipiravir and aspirin in ethanol showed overlapping emission spectra at 423 nm and 403 nm, respectively, after excitation at 368 nm and 298 nm, respectively. Direct simultaneous determination with normal fluorescence spectroscopy was difficult. The use of synchronous fluorescence spectroscopy for analyzing the studied drugs in ethanol at Δλ = 80 nm improved spectral resolution and enabled the determination of favipiravir and aspirin in the plasma matrix at 437 nm and 384 nm, respectively. The method described allowed sensitive determination of favipiravir and aspirin over a concentration range of 10-500 ng/mL and 35-1600 ng/mL, respectively. The described method was validated with respect to the ICH M10 guidelines and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in the spiked plasma matrix. Moreover, the compliance of the method with the concepts of environmentally friendly analytical chemistry was evaluated using two metrics, the Green Analytical Procedure Index and the AGREE tool. The results showed that the described method was consistent with the accepted metrics for green analytical chemistry.

Clinical study to compare the efficacy and safety of casirivimab & imdevimab, remdesivir, and favipravir in hospitalized COVID-19 patients.

Background: Corona Virus disease - 2019 (COVID-19) disease induces scientific research to find a control to this pandemic from 2020 year up to now. Recently, various advances in pharmacotherapy against COVID-19 have emerged. Objectives: To compare the efficacy and safety of antibodies cocktail (casirivimab and imdevimab), Remdesivir, and Favipravir in the COVID-19 patients. Study design: This study is a single-blind non-Randomized Controlled Trial (non-RCT). The drugs of the study are prescribed by lectures on chest diseases, faculty of medicine-Mansoura University. The duration of the study is about six months after ethical approval.265 hospitalized COVID-19 patients were used to represent the COVID-19 population and were assigned into three groups in a ratio of (1:2:2) respectively, Group (A) received REGN3048-3051(Antibodies cocktail (casirivimab and imdevimab)), group (B) received remdesivir, and group (C) received favipravir. Results: Casirivimab and imdevimab achieve less 28-day mortality rate, and less mortality at hospital discharge than Remdesivir, and Favipravir. Conclusion: From all of these results, it is concluded that Group A (Casirivimab & imdevimab) achieves more favorable outcomes than B (Remdesivir) & C (Favipravir) intervention groups. Clinical trial registration: NCT05502081, 16/08/2022, Clinicaltrials.gov.

The state of health in Pakistan and its provinces and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding health trends and estimating the burden of disease at the national and subnational levels helps policy makers track progress and identify disparities in overall health performance. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides comprehensive estimates for Pakistan. Comparison of health indicators since 1990 provides valuable insights about Pakistan's ability to strengthen its health-care system, reduce inequalities, improve female and child health outcomes, achieve universal health coverage, and meet the UN Sustainable Development Goals. We present estimates of the burden of disease, injuries, and risk factors for Pakistan provinces and territories from 1990 to 2019 based on GBD 2019 to improve health and health outcomes in the country. Methods We used methods and data inputs from GBD 2019 to estimate socio-demographic index, total fertility rate, cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years, healthy life expectancy, and risk factors for 286 causes of death and 369 causes of non-fatal health loss in Pakistan and its four provinces and three territories from 1990 to 2019. To generate estimates for Pakistan at the national and subnational levels, we used 68 location-years of data to estimate Pakistan-specific demographic indicators, 316 location-years of data for Pakistan-specific causes of death, 579 location-years of data for Pakistan-specific non-fatal outcomes, 296 location-years of data for Pakistan-specific risk factors, and 3089 location-years of data for Pakistan-specific covariates. Findings Life expectancy for both sexes in Pakistan increased nationally from 61 center dot 1 (95% uncertainty interval [UI] 60 center dot 0-62 center dot 1) years in 1990 to 65 center dot 9 (63 center dot 8-67 center dot 8) years in 2019;however, these gains were not uniform across the provinces and federal territories. Pakistan saw a narrowing of the difference in healthy life expectancy between the sexes from 1990 to 2019, as health gains for women occurred at faster rates than for men. For women, life expectancy increased by 8 center dot 2% (95% UI 6middot3-13middot8) between 1990 and 2019, whereas the male life expectancy increased by 7 center dot 6% (3 center dot 5-11 center dot 8). Neonatal disorders, followed by ischaemic heart disease, stroke, diarrhoeal diseases, and lower respiratory infections were the leading causes of all-age premature mortality in 2019. Child and maternal malnutrition, air pollution, high systolic blood pressure, dietary risks, and tobacco consumption were the leading all-age risk factors for death and disability-adjusted life-years at the national level in 2019. Five non-communicable diseases-ischaemic heart disease, stroke, congenital defects, cirrhosis, and chronic kidney disease-were among the ten leading causes of years of life lost in Pakistan. Burden varied by socio-demographic index. Notably, Balochistan and Khyber Pakhtunkhwa had the lowest observed gains in life expectancy. Dietary iron deficiency was the leading cause of years lived with disability for both men and women in 1990 and 2019. Low birthweight and short gestation and particulate matter pollution were the leading contributors to overall disease burden in both 1990 and 2019 despite moderate improvements, with a 23 center dot 5% (95% UI 3 center dot 8-39 center dot 2) and 27 center dot 6% (14 center dot 3-38 center dot 6) reduction in age-standardised attributable DALY rates during the study period. Interpretation Our study shows that progress has been made on reducing Pakistan's disease burden since 1990, but geographical, age, and sex disparities persist. Equitable investment in the health system, as well as the prioritisation of high-impact policy interventions and programmes, are needed to save lives and improve health outcomes. Pakistan is facing several domestic and foreign challenges-the Taliban's return to power in Afghanistan, political turmoil, catastrophic flooding, the COVID-19 pandemic-that will shape the trajectory of the country's health and development. Pakistan must address the burden of infectious disease and curb rising rates of non-communicable diseases. Prioritising these three areas will enhance Pakistan's ability to achieve universal health coverage, meet its Sustainable Development Goals, and improve the overall health outcomes.

The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats.

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

Harnessing immunoinformatics for developing a multiple-epitope peptide-based vaccination approach against SARS-CoV-2 spike protein.

COVID-19 has spread to over 200 countries with variable severity and mortality rates. Computational analysis is a valuable tool for developing B-cell and T-cell epitope-based vaccines. In this study, by harnessing immunoinformatics tools, we designed a multiple-epitope vaccine to protect against COVID-19. The candidate epitopes were designed from highly conserved regions of the SARS-CoV-2 spike (S) glycoprotein. The consensus amino acids sequence of ten SARS-CoV-2 variants including Gamma, Beta, Epsilon, Delta, Alpha, Kappa, Iota, Lambda, Mu, and Omicron was involved. Applying the multiple sequence alignment plugin and the antigenic prediction tools of Geneious prime 2021, ten predicted variants were identified and consensus S-protein sequences were used to predict the antigenic part. According to ElliPro analysis of S-protein B-cell prediction, we explored 22 continuous linear epitopes with high scores ranging from 0.879 to 0.522. First, we reported five promising epitopes: BE1 1115-1192, BE2 481-563, BE3 287-313, BE4 62-75, and BE5 112-131 with antigenicity scores of 0.879, 0.86, 0.813, 0.779, and 0.765, respectively, while only nine discontinuous epitopes scored between 0.971 and 0.511. Next, we identified 194 Major Histocompatibility Complex (MHC) - I and 156 MHC - II epitopes with antigenic characteristics. These spike-specific peptide-epitopes with characteristically high immunogenic and antigenic scores have the potential as a SARS-CoV-2 multiple-epitope peptide-based vaccination strategy. Nevertheless, further experimental investigations are needed to test for the vaccine efficacy and efficiency.

Strategic response to COVID-19 in Ethiopia.

COVID-19, the novel coronavirus, has posed a major threat to low- and middle-income countries (LMICs) due to inadequate health infrastructure and human resources. Ethiopia, a low-income country with the second largest population in Africa, has coordinated a strategic response, leveraging existing infrastructure and health systems and mobilizing public health professionals and specialist expert physicians for a multifaceted, unified government approach and adaptive response. Resource limitations, particularly in critical care, have still posed challenges, but the public health and clinical interventions thus far have prevented the catastrophic toll that many predicted. As the pandemic continues, Ethiopia expects to use a triple care model integrated at all levels, consisting of COVID-19 care, isolation care for suspected cases, and essential health services, and urges intensified non-pharmaceutical interventions alongside equitable global vaccine distribution as the ultimate answers to pandemic control. This paper draws on existing data, national planning and guidelines, and expertise from health leadership to describe this response in hopes of providing an example of how future large-scale health challenges might be faced in LMICs, using Ethiopia's successes and challenges in facing the pandemic.

COVID-19, le nouveau coronavirus, a représenté une menace majeure pour les pays à revenu faible et intermédiaire (LMIC) en raison de l'insuffisance des infrastructures de santé et des ressources humaines. L'Éthiopie, un pays à faible revenu dont la population est la deuxième plus importante d'Afrique, a coordonné une réponse stratégique, en tirant parti des infrastructures et des systèmes de santé existants et en mobilisant des professionnels de la santé publique et des médecins experts spécialisés pour une approche gouvernementale unifiée à multiples facettes et une réponse adaptative. Les ressources limitées, notamment en matière de soins intensifs, ont encore posé des problèmes, mais les interventions cliniques et de santé publique menées jusqu'à présent ont permis d'éviter le bilan catastrophique que beaucoup prédisaient. Alors que la pandémie se poursuit, l'Éthiopie prévoit d'utiliser un modèle de soins triple intégré à tous les niveaux, composé de soins COVID-19, de soins d'isolement pour les cas suspects et de services de santé essentiels, et préconise l'intensification des interventions non pharmaceutiques parallèlement à une distribution équitable des vaccins à l'échelle mondiale comme réponses ultimes au contrôle de la pandémie. Cet article s'appuie sur les données existantes, la planification et les directives nationales, et l'expertise des responsables de la santé pour décrire cette réponse dans l'espoir de fournir un exemple de la manière dont les futurs défis sanitaires à grande échelle pourraient être relevés dans les LMIC, en utilisant les succès et les défis de l'Éthiopie face à la pandémie.

Building a Real-Time System to Monitor Students Electronically Based on Digital Images of Face Movement

The spread of the Corona Virus pandemic on a global scale had a great impact on the trend towards e-learning. In the virtual exams the student can take his exams online without any papers, in addition to the correction and electronic monitoring of the exams. Tests are supervised and controlled by a camera and proven cheat-checking tools. This technology has opened the doors of academic institutions for distance learning to be wide spread without any problems at all. In this paper, a proposed model was built by linking a computer network using a server/client model because it is a system that distributes tasks between the two. The main computer that acts as a server (exam observer) is connected to a group of sub-computers (students) who are being tested and these devices are considered the set of clients. The proposed student face recognition system is run on each computer (client) in order to identify and verify the identity of the student. When another face is detected, the program sends a warning signal to the server. Thus, the concerned student is alerted. This mechanism helps examinees reduce cheating cases in early time. The results obtained from the face recognition showed high accuracy despite the large number of students' faces. The performance speed was in line with the test performance requirements, handling 1,081 real photos and adding 960 photos. © 2022 IEEE.

Mental health training needs of physicians in Bangladesh: Views from stakeholders

Bangladesh is a lower-middle-income country with a high burden of mental health conditions and inadequate health systems. Prior research in similar settings has found that training physicians in mental health literacy can contribute to reducing the mental health treatment gap and strengthening the mental health care pathway. This study explores the need for mental health training for physicians by gathering stakeholders' perspectives and proposes recommendations for designing a mental training program in the context of Bangladesh. Key informant interviews were conducted among psychiatrists (n = 9), and mental health entrepreneurs (n = 7);one focus group discussion was conducted with psychologists (n = 8);and one-on-one interviews were held with physician (n = 17). Due to the COVID-19 restrictions, all interviews were conducted online, recorded and transcribed. Transcriptions were analyzed thematically, utilizing both an inductive and deductive approach. The data analysis from forty-one stakeholders generated three major themes and eight subthemes. Stakeholders perceived that the inadequate mental health system and low mental health awareness among physicians significantly contribute to the mental health treatment gaps. Stakeholders emphasized the need to include mental health training for physicians to increase skills related to identification and management of mental health conditions. Stakeholders suggested some basic components for the training content, feasible modalities to deliver the training, and implementation challenges. Recommendations included utilizing online training, ensuring interesting and practical content, and incorporating certification systems. At a systems level, stakeholders recommended including a mental health curriculum in undergraduate medical education, capacity building of other healthcare workers and increasing awareness at the policy level. There is clear agreement among stakeholders that implementing mental health training for physicians will promote universal health coverage and reduce the mental health treatment gap in Bangladesh. These findings can support creation of policies to strengthen the care pathway in countries with limited resources.Copyright © 2022 The Authors

Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial.

Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.

Simultaneous green TLC determination of nirmatrelvir and ritonavir in the pharmaceutical dosage form and spiked human plasma.

Quantitative analysis of pharmaceutical compounds up to Nano gram levels is highly recommended to introduce feasible and sensitive tool for determination of the compounds in the pharmaceutical and biological samples. Nirmatrelvir plus ritonavir was recently approved in the US, the UK and Europe as a new co-packaged dosage form for the treatment of COVID-19. The objective of this work was to develop a more sensitive TLC method based on using ß-cyclodextrin as a chiral selector additive in the mobile phase for simultaneous determination of nirmatrelvir and ritonavir in pure form, pharmaceutical formulation and spiked human plasma. The analysis procedures were developed using TLC aluminum silica gel plates and methanol-water- 2% urea solution of ß-cyclodextrin (40:10:.5, by volume) as a mobile phase with UV detection at 215 nm. The developed method was successfully applied over a linearity range of 10-50 ng/band for both nirmatrelvir and ritonavir. The method was validated for limits of detection and quantitation, accuracy, precision, specificity, system suitability, and robustness. Furthermore, the eco-friendliness of the proposed method was assessed using the analytical eco-scale and the green analytical procedure index. The described method exhibited compliance with green analytical chemistry principles based on common green metric values.

Effect of Nebulized BromAc on Rheology of Artificial Sputum: Relevance to Muco-Obstructive Respiratory Diseases.

Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions.

Covid-19 Variants Detection and Classification Using Self Proposed Two stage MNN-2: Robust Comparison with Yolo V5 and Faster R-CNN

Covid-19 is unpredictable evolutionary discipline which requires continuous advancements for its appropriate Detection and Classifications which can be helpful for bio-medical stream. In this research, two dimensions are covered that is detection and classification using self-proposed 2 stage learning detector. Detection of different variants of Covid-19 are performed using images of CT-Scan and X-Rays of effected lungs. Furthermore, classification of different variants is carried out. Dataset of 27000 indigenous images were used for detection and classification purposed. Moreover, in depth survey and comparison is carried out with state-of-the-art Yolo v5 single state detector and Faster R-CNN 2 stage detector. Accuracy analysis of self-proposed 2 stage detector was 91.66% and 87.9% for detection and classification in comparison with YOLOv5 which had accuracy of 92.8% and 87.175% for detection and classification. Moreover, in comparison with Faster R-CNN which had accuracy of 94.8% and 87% The training analysis was performed on Nvidia T4 (16GB GDDR6). Self-proposed MNN-2 superseded Yolov5 and faster R-CNN in real time video analysis with least real time rate at FPS 30 at duration of 72 min video. © 2022 IEEE.

COVID-19 and Digitizing Accounting Education: Theory and Literature Review

This article critically analyzes previously published literature and discusses the lessons learned in detail. Learning gleaned from the theories has been used to create a conceptual framework. Using data from the published sources, a null hypothesis is developed to suit the current case. The results highlight the importance of digitalization in education in general and the accounting field in particular. This paper also reveals the impact of COVID-19 on education and addresses the main challenges faced by education and the accounting sector after the pandemic. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

SARS-CoV-2 infection and smoking: What is the association? A brief review.

Susceptibility to severe illness from COVID-19 is anticipated to be associated with cigarette smoking as it aggravates the risk of cardiovascular and respiratory illness, including infections. This is particularly important with the advent of a new strain of coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) that has led to the present pandemic, coronavirus disease 2019 (COVID-19). Although, the effects of smoking on COVID-19 are less described and controversial, we presume a link between smoking and COVID-19. Smoking has been shown to enhance the expression of the angiotensin-converting enzyme-2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) key entry genes utilized by SARS-CoV-2 to infect cells and induce a 'cytokine storm', which further increases the severity of COVID-19 clinical course. Nevertheless, the impact of smoking on ACE-2 and TMPRSS2 receptors expression remains paradoxical. Thus, further research is necessary to unravel the association between smoking and COVID-19 and to pursue the development of potential novel therapies that are able to constrain the morbidity and mortality provoked by this infectious disease. Herein we present a brief overview of the current knowledge on the correlation between smoking and the expression of SARS-CoV-2 key entry genes, clinical manifestations, and disease progression.