Evaluation of oral health-related quality of life and its association with mental health status of patients with type 2 diabetes mellitus in the post-COVID-19 pandemic era: A study from Central Saudi Arabia.

Background and objectives: The association between oral and mental health is reciprocal, in which poor oral health may lead to several mental health issues, especially among patients with diabetes. The present study evaluated oral health-related quality of life (OHRQOL) and its association with mental health conditions among patients with type 2 diabetes mellitus (T2DM) in central Saudi Arabia. Methods: The Arabic version of the Oral Health Impact Profile-14 (OHIP-14) questionnaire and the Depression, Anxiety, and Stress Scale-21 Items (DASS-21) were used to assess the OHRQOL and mental health status of patients with diabetes. We utilized logistic regression analysis to identify the predictors of poor OHRQOL, and Spearman's correlation test to identify any correlations between OHIP-14 and overall DASS-21 scores, as well as each subscale. Results: Of the 677 patients included in the present study, 52.7% had a poor OHRQOL, which was significantly higher (positive association) among patients with a longer duration of diabetes (adjusted odds ratio [AOR] = 3.31; 95% confidence interval [CI] = 1.96-4.17) and those who did not periodically monitor their oral health (AOR = 2.85; 95% CI = 1.76-3.89). Some forms (mild, moderate, severe, or extremely severe) of depression, anxiety, and stress were observed in 59.7, 71.1, and 67.1% of the participants, respectively. Furthermore, we found that the total OHRQOL scores had a significant positive association with depression (AOR = 2.32, 95% CI = 1.34-3.71, p = 0.001), anxiety (AOR = 1.81, 95% CI = 1.22-2.79, p = 0.003), and stress (AOR = 1.43, 95% CI = 1.14-2.19, p = 0.026). Conclusion: The results of the present study suggest the importance of appropriate and targeted health education programs for T2DM patients to ensure periodic dental examinations and oral health. Additionally, we recommend counseling sessions for all T2DM patients with trained healthcare providers to improve their mental health status during follow-up visits at outpatient diabetes care centers.

Agitation of SARS‐CoV‐2 disease (COVID‐19) using ABC$$ \mathbf{ABC} $$ fractional‐order modified SEIR model

The present article studies the agitation scenario of SARS‐CoV‐2 (COVID‐19), the current pandemic around the globe, by applying Atangana–Baleanu–Caputo (ABC)$$ \left(\mathcal{ABC}\right) $$ derivative operator where 0<κ≤1$$ 0<\kappa \le 1 $$. Using classical notions, we study various qualitative features, like existence, uniqueness and investigate Hyers–Ulam stability analysis of the model under consideration. Lagrange's polynomial approach is used for the approximation of nonlinear terms of the system. We carry out numerical simulations for different values of the fractional‐order κ$$ \kappa $$. The results obtained are compared with those of the classic order derivatives. It is observed that the results obtained with fractional order are better as compared to the classical order. [ABSTRACT FROM AUTHOR] Copyright of Mathematical Methods in the Applied Sciences is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Factors affecting knowledge, attitude, and practice of COVID-19: A study among undergraduate university students in Bangladesh.

The global expansion of the COVID-19 outbreak is one of the worst disasters the world has faced in recent decades. This study explored various factors of knowledge, attitude, and practice regarding COVID-19 among Bangladeshi undergraduate university students. In addition, we also look at how COVID-19 based knowledge, attitude, and practice influence each other. Using a random sampling technique and a self-administered structured questionnaire survey, this study collected data from 167 private university students in Bangladesh from 1st October to 30th October 2020. Data were analyzed using descriptive statistics (including frequencies, percentages, and means), binary logistic regression, bivariate regression analysis, and factor analysis. The findings suggest that most of the students learned about COVID-19 from various sources, including news media (TV, radio, newspapers, etc.), international organizations (WHO, UN, etc.), various government programs, or from their friends, family members, or neighbors. Most of the students were concerned about becoming sick, keeping social distance, and family members' job insecurity, followed by the university shutdown and the subsequent quarantine. Many students believe Bangladesh's media, government, medical sector, and religious organizations played a significant role during COVID-19. Binary logistic regression demonstrates that students' gender, department, and residency significantly explained their COVID-19 knowledge. In addition, students' attitudes significantly vary with their religion and place of residence. Students' departments and semesters found significant in explaining their practice regarding COVID-19. Moreover, factor analysis results also identified several crucial factors in explaining students' overall knowledge, attitude, and practice of COVID-19. Finally, we found a statistically significant relationship between knowledge, attitude, and practice.

Early Side Effects after Administration of the 1st Dose of Oxford-AstraZeneca Vaccine (preprint)

Vaccines have played a central role in minimizing new infections, the rate of hospitalizations, and the overall burden on the health sector. Fear of side effects is the biggest and commonest reason for avoiding getting vaccinated. It is, therefore, essential to maintain the clarity and consistency of message, to support and encourage people to get vaccinated. This study aims to contribute in that regard, by registering and quantifying the early side-effects of the Oxford-AstraZeneca COVID-19 vaccine in Pakistan. This study employs a non-random cross-sectional design. Data collected from 477 participants using a structured questionnaire was used to investigate the relationship between socio-demographic characteristics and side effect profiles of the participants. Binomial Logistic Regression was used to analyze the data. Odds Ratio (OR) gives the likelihood of having a side effect versus the reference group. Significance level () for the probability value (p-value) is set at 0.05. Fever (30.19%) was the most commonly experienced side effect, followed closely by fatigue (22.01%). 71.11% of those with fever experienced low grade fever (99-100F) while 62.69% of body aches experienced were moderate in intensity (Grades 4-6). In general, younger people are significantly more likely (p=0.023) to experience side effects (OR -1 = 1.023: interpreted as 1.023 times increase per unit decrease in age). Similarly, they are more likely (p= 0.029) to have a headache (OR -1 =1.039). Also, they are more likely (p= 0.007) to have a body ache (OR -1 =1.038). The Oxford-AstraZeneca COVID-19 vaccine side-effects seem to be more prevalent among younger age groups, which points to increased vaccine safety among older individuals that are usually more susceptible to severe COVID-19 infection. In addition, we found a substantially reduced number of side-effects, as compared to the clinical trials, which is an encouraging indicator for vaccine safety.

Comprehensive Phytochemical Profiling, Biological Activities, and Molecular Docking Studies of Pleurospermum candollei: An Insight into Potential for Natural Products Development.

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.

Modeling and analysis of a fractional anthroponotic cutaneous leishmania model with Atangana-Baleanu derivative.

Very recently, Atangana and Baleanu defined a novel arbitrary order derivative having a kernel of non-locality and non-singularity, known as AB derivative. We analyze a non-integer order Anthroponotic Leshmania Cutaneous (ACL) problem exploiting this novel AB derivative. We derive equilibria of the model and compute its threshold quantity, i.e. the so-called reproduction number. Conditions for the local stability of the no-disease as well as the disease endemic states are derived in terms of the threshold quantity. The qualitative analysis for solution of the proposed problem have derived with the aid of the theory of fixed point. We use the predictor corrector numerical approach to solve the proposed fractional order model for approximate solution. We also provide, the numerical simulations for each of the compartment of considered model at different fractional orders along with comparison with integer order to elaborate the importance of modern derivative. The fractional investigation shows that the non-integer order derivative is more realistic about the inner dynamics of the Leishmania model lying between integer order.

Cost of Goods Analysis Facilitates an Integrated Approach to Identifying Alternative Synthesis Methodologies for Lower Cost Manufacturing of the COVID-19 Antiviral Molnupiravir.

Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets. Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses. While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings. While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.

Cost of Goods Analysis Facilitates an Integrated Approach to Identifying Alternative Synthesis Methodologies for Lower Cost Manufacturing of the COVID-19 Antiviral Molnupiravir [version 1;peer review: 2 approved]

Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets. Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses. While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings. While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.

Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis.

A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.

PFOA induces alteration in DNA methylation regulators and SARS-CoV-2 targets Ace2 and Tmprss2 in mouse lung tissues.

Perfluorooctanoic acid (PFOA), a ubiquitous environmental toxicant from the Per- and polyfluoroalkyl substances (PFAS) family has been implicated in toxicity of various organs. Several epidemiological studies have linked PFOA to different lung injuries and diseased conditions. However, the implication of PFOA in affecting epigenetic regulators and SARS-CoV-2 infection pathways in the lung are unknown. The present work explores the accumulation of PFOA in lungs and changes in mRNA expression of DNA methylation regulator genes DNA methyltransferases (Dnmts) and ten-eleven translocation (Tets) along with the membrane proteins angiotensin converting enzyme 2 (Ace2) and transmembrane Serine Protease 2 (Tmprss2) genes involved in the SARS-CoV-2 virus infection. CD1 mice were orally exposed to 5 and 20 mg/kg/day PFOA for 10 days and the lung tissues were analyzed using LCMS, qPCR, and pyrosequencing techniques. PFOA was shown to accumulate in the lung tissues and increase in a dose-dependent manner. Dnmts and Tets were significantly downregulated upon at least one of the PFOA dosing concentration, whereas Ace2 and Tmprss2 show significant increase in their expression level. Further, CpG islands in the promotor region of Tmprss2 exhibited significant hypomethylation in PFOA treated groups, which supports its increased gene expression level. Current study reveals the implication of PFOA induced DNA methylation changes in lungs and their possible role in upregulation of Ace2 and Tmprss2. It is possible that increased expression of these membrane receptors due to PFOA exposure can lead to higher susceptibility of SARS-CoV-2 infections.

Can a quantitative assessment of SARS-CoV-2 PCR predict degree of severity and outcomes in critical care patients with COVID-19?

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim, in this retrospective study, was to determine the impact of serial SARS-CoV-2 qPCR Ct-values on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) with COVID-19. Ct values were evaluated during the time points from pre-ICU admission to week 1, week 2 and week 3 during ICU stay; impact on mortality, need for MV and AKI was determined. There was a continuous increment in Ct-values over the ICU stay from 1st week through to 3rd week. Although not significant, lower ICU 1st week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20. This report shows that the impact of Ct-values and outcomes, especially AKI, among patients at different time points prior to and during ICU stay, larger studies are required to confirm out findings.

Pain and satisfaction: the case of isolated COVID-19 patients of Pakistan.

BACKGROUND: Over 3 million people lost their lives across the globe due to the COVID-19 related pandemic. The unprecedented restrictions on mobility have imposed in the form of isolation, quarantines, and lockdowns to curb the profound effects of the pandemic and retain physical health. This study examined the relationship between various pain levels, demographic variables and patient satisfaction with COVID-19 during isolation. METHODS: The primary data in this study were collected from isolated patients during their isolation and treatment in a public hospital. We obtained information from patients with COVID-19 (N = 100) about their demographic characteristics, varying levels of pain, and satisfaction with the services provided during the isolation period. We computed the descriptive statistics to explain the profile of participants, ANOVA was used to find out the difference between various groups on patient satisfaction, and structural equation modeling was performed to examine the link between pain levels, demographic factors, and patient satisfaction. This analysis was performed with STATA and SmartPLS-3. RESULTS: The findings of this study ascertained that respondent's education (Beta, ß = 2.961, p = 0.003), assets such as possession of a house (ß = 4.563, p = 0.000), perception of income adequacy during the lockdown (=2.299, p = 0.022), and negligence in prevention (ß = 1.975, p = 0.049) significantly affects patient satisfaction during the isolation period. Moreover, satisfaction with life, physicians and medicine, income adequacy, and fear of the participants was significantly linked to the pain level (Model F-stat = 86.323, p = 0.0001). Patients who were satisfied with their treatment had significantly lower odds of having pain (OR 0.023, 95% CI [0.001-0.0452]). Patients who had enough income to meet their basic necessities were found to have significantly lower odds of having pain (OR 0.155, 95% CI [0.032-0.740]. DISCUSSION AND CONCLUSION: We conclude that a higher level of education, low income, and living in a rented house contributes significantly to the feeling of more satisfaction with the provided services. This implies that people with more affluent backgrounds are less likely to be satisfied with the provided services as low-income and living in rented house groups are more satisfied during isolation than others. The pain level is also affected by subjective factors such as fear and satisfaction which need to be considered while doing patient management. This study can be helpful in improving the delivery of public services of isolation centers by considering various characteristics and demographic factors of patients.

Study on the mathematical modelling of COVID-19 with Caputo-Fabrizio operator.

In this article we study a fractional-order mathematical model describing the spread of the new coronavirus (COVID-19) under the Caputo-Fabrizio sense. Exploiting the approach of fixed point theory, we compute existence as well as uniqueness of the related solution. To investigate the exact solution of our model, we use the Laplace Adomian decomposition method (LADM) and obtain results in terms of infinite series. We then present numerical results to illuminate the efficacy of the new derivative. Compared to the classical order derivatives, our obtained results under the new notion show better results concerning the novel coronavirus model.

Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine.

Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on a decagram scale: the first step at 200 g and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.

Impact of pangolin bootleg market on the dynamics of COVID-19 model.

In this paper we consider ant-eating pangolin as a possible source of the novel corona virus (COVID-19) and propose a new mathematical model describing the dynamics of COVID-19 pandemic. Our new model is based on the hypotheses that the pangolin and human populations are divided into measurable partitions and also incorporates pangolin bootleg market or reservoir. First we study the important mathematical properties like existence, boundedness and positivity of solution of the proposed model. After finding the threshold quantity for the underlying model, the possible stationary states are explored. We exploit linearization as well as Lyapanuv function theory to exhibit local stability analysis of the model in terms of the threshold quantity. We then discuss the global stability analyses of the newly introduced model and found conditions for its stability in terms of the basic reproduction number. It is also shown that for certain values of R 0 , our model exhibits a backward bifurcation. Numerical simulations are performed to verify and support our analytical findings.

Can a Quantitative Assessment of SARS-CoV-2 PCR Predict Degree of Severity and Outcomes in Critical Care Patients with COVID-19 (preprint)

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for acute SARS-CoV-2 infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim in this retrospective study was to determine the impact of serial SARS-CoV-2 qPCR Ct-values, among critically ill COVID-19 patients both prior and during intensive care unit (ICU) stay, on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI). There was a continuous increment in Ct-values over the ICU stay from 1st-week through to 3rd-week. Although not significant, lower ICU 1st-week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20.To our knowledge this is the first report showing the impact of Ct-values and outcomes, especially AKI, among patients at different time point’s prior to and during ICU stay. 

Mathematical analysis of COVID-19 via new mathematical model.

We develop a new mathematical model by including the resistive class together with quarantine class and use it to investigate the transmission dynamics of the novel corona virus disease (COVID-19). Our developed model consists of four compartments, namely the susceptible class, S ( t ) , the healthy (resistive) class, H ( t ) , the infected class, I ( t ) and the quarantine class, Q ( t ) . We derive basic properties like, boundedness and positivity, of our proposed model in a biologically feasible region. To discuss the local as well as the global behaviour of the possible equilibria of the model, we compute the threshold quantity. The linearization and Lyapunov function theory are used to derive conditions for the stability analysis of the possible equilibrium states. We present numerical simulations to support our investigations. The simulations are compared with the available real data for Wuhan city in China, where the infection was initially originated.

Investigations, actions and learning from an outbreak of SARS-CoV-2 infection among healthcare workers in the United Kingdom.

BACKGROUND: We report an outbreak of SARS coronavirus-2 (SARS-CoV-2) infection among healthcare workers (HCW) in an NHS elective healthcare facility. METHODOLOGY: A narrative chronological account of events after declaring an outbreak of SARS-CoV-2 among HCWs. As part of the investigations, HCWs were offered testing during the outbreak. These were: (1) screening by real-time reverse transcriptase polymerase chain reaction (RT- PCR) to detect a current infection; and (2) serum samples to determine seroprevalence. RESULTS: Over 180 HCWs were tested by real-time RT-PCR for SARS-CoV-2 infection. The rate of infection was 15.2% (23.7% for clinical or directly patient-facing HCWs vs. 4.8% in non-clinical non-patient-facing HCWs). Of the infected HCWs, 57% were asymptomatic. Seroprevalence (SARS-CoV-2 IgG) among HCWs was 13%. It was challenging to establish an exact source for the outbreak. The importance of education, training, social distancing and infection prevention practices were emphasised. Additionally, avoidance of unnecessary transfer of patients and minimising cross-site working for staff and early escalation were highlighted. Establishing mass and regular screening for HCWs are also crucial to enabling the best care for patients while maintaining the wellbeing of staff. CONCLUSION: To our knowledge, this is the first UK outbreak report among HCWs and we hope to have highlighted some key issues and learnings that can be considered by other NHS staff and HCWs globally when dealing with such a task in future.