Microfluidic Organ-Chips and Stem Cell Models in the Fight Against COVID-19.

SARS-CoV-2, the virus underlying COVID-19, has now been recognized to cause multiorgan disease with a systemic effect on the host. To effectively combat SARS-CoV-2 and the subsequent development of COVID-19, it is critical to detect, monitor, and model viral pathogenesis. In this review, we discuss recent advancements in microfluidics, organ-on-a-chip, and human stem cell-derived models to study SARS-CoV-2 infection in the physiological organ microenvironment, together with their limitations. Microfluidic-based detection methods have greatly enhanced the rapidity, accessibility, and sensitivity of viral detection from patient samples. Engineered organ-on-a-chip models that recapitulate in vivo physiology have been developed for many organ systems to study viral pathology. Human stem cell-derived models have been utilized not only to model viral tropism and pathogenesis in a physiologically relevant context but also to screen for effective therapeutic compounds. The combination of all these platforms, along with future advancements, may aid to identify potential targets and develop novel strategies to counteract COVID-19 pathogenesis.

SNAP@CQD as a promising therapeutic vehicle against HCoVs: an overview

Graphical This report discusses potential therapies for treating human coronaviruses (HCoVs) and their economic impact. Specifically, we explore therapeutics that can support the body's immune response, including immunoglobulin (Ig)A, IgG and T-cell responses, to inhibit the viral replication cycle and improve respiratory function. We hypothesize that carbon quantum dots conjugated with S-nitroso-N-acetylpenicillamine (SNAP) could be a synergistic alternative cure for treating respiratory injuries caused by HCoV infections. To achieve this, we propose developing aerosol sprays containing SNAP moieties that release nitric oxide and are conjugated onto promising nanostructured materials. These sprays could combat HCoVs by inhibiting viral replication and improving respiratory function. Furthermore, they could potentially provide other benefits, such as providing novel possibilities for nasal vaccines in the future. Teaser: Synergistic effect of carbon quantum dots and S-nitroso-N-acetylpenicillamine (SNAP) could be suggested as an alternative treatment for the respiratory damage caused by HCoV infections that further open possibilities of developing novel nasal vaccines.

Modeling Cardiac SARS-CoV-2 Infection with Human Pluripotent Stem Cells.

Although SARS-CoV-2, the causative virus of the global COVID-19 pandemic, primarily affects the respiratory tract, it is now recognized to have broad multi-organ tropism and systemic effects. Early reports indicated that SARS-CoV-2 infection could lead to cardiac damage, suggesting the virus may directly impact the heart. Cardiac cell types derived from human pluripotent stem cells (hPSCs) enable mechanistic interrogation of SARS-CoV-2 infection in human cardiac tissue. PURPOSE OF REVIEW: To review the studies published since the emergence of the COVID-19 pandemic which utilize hPSCs and their cardiovascular derivative cell types to interrogate the tropism and effects of SARS-CoV-2 infection in the heart, as well as explore potential therapies. RECENT FINDINGS: Recent studies reveal that SARS-CoV-2 is capable of infecting and replicating within hPSC-derived cardiomyocytes and sinoatrial nodal cells, but not as extensively in their non-parenchymal counterparts. Additionally, they show striking viral effects on cardiomyocyte structure, transcriptional activity, and survival, along with potential mechanisms and therapeutic targets. Cardiac models derived from hPSCs are a viable platform to study the impact of SARS-CoV-2 on cardiac tissue and may lead to novel mechanistic insight as well as therapeutic interventions.

Assessment of Understanding and Practices of Community Pharmacy Personnel to Tackle COVID-19 Pandemic.

BACKGROUND: The skill, accessibility, and knowledge of community pharmacists have been paramount in managing pandemics. This study was conducted to assess the knowledge, attitude, and practice of community pharmacy personnel towards tackling COVID-19 pandemic which might help concerned authorities to take effective actions to eliminate the gaps for the management of such pandemic in an efficient way. METHODS: A cross-sectional study was conducted among 428 community pharmacy personnel from different community pharmacies in Kathmandu, Nepal from December 2021 to February 2022. Statistical analysis was done through SPSS® v21 and MedCalc for Windows v12.3.0. RESULTS: Most of the participants (42.76%) had certificate-level degrees in their respective fields and one to five years of working experience (48.84%). Only 29.67% of the respondents had good knowledge towards tackling COVID-19, whereas good attitude and practice were demonstrated by 59.11% and 42.29% respectively. The participants with higher degrees and more working experience had better knowledge, attitude, and practice. Education level bachelor and above was independent predictor of good knowledge (OR 20.69, 95% CI 11.30-37.90). Knowledge and practice (Spearman's rho: 0.135; P ≤0.005) and attitude and practice (Spearman's rho: 0.095; P = 0.049) scores were positively correlated. CONCLUSIONS: The significant association of community pharmacy personnel's educational level with knowledge, attitude, and practices demands the necessity of policy-making bodies' involvement for the mandatory presence of well-qualified pharmacists and regular training at the community pharmacy level. Furthermore, it is high time to reinforce the drug regulatory acts, regulations, and codes all over the nation.

Understanding salespeople's resistance to, and acceptance and leadership of customer-driven change

Salespeople's responses to change have been extensively examined in the context of sales literature, sales force automation (SFA), customer relationship management (CRM) systems, and other sales technologies. The majority of sales technology changes were typically organization driven. In contrast, during the COVID-19 pandemic, salespeople faced changing sales processes that were increasingly customer-driven. We seek a deeper understanding of salespeople's acceptance of customer-driven change and interview 38 sales professionals to enhance our understanding of salespeople's perceptions and behaviors. Our findings show an increase in the use of technology, increased marketing-sales integration, and shifts in sales processes and organizations. We identify three profiles of salespeople: those that resist change, accept change, and lead change. We find differences in salespeople driven by their perceptions of customer environments and their capabilities, sales management function, and organization factors relevant in defining attitude toward change. We consequently derive implications for theory and practice.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Breakthroughs in Medicinal Chemistry [...].

Predictors of Professional Fulfillment and Burnout Among Otolaryngologists During the COVID-19 Pandemic.

Objective: The goal of this study is to assess burnout and professional fulfillment during the initial weeks of the COVID-19 pandemic among otolaryngology practitioners. Study Design: Cross-sectional survey. Setting: International survey of otolaryngologists during a pandemic. Methods: A cross-sectional survey was performed from April 24 to May 8, 2020, via email and social media platforms to understand the impact of the COVID-19 pandemic on otolaryngology practitioners in academic and private practice. The Professional Fulfillment Index was used to assess professional fulfillment and burnout. Burnout was divided into work exhaustion and interpersonal disengagement. Results: Of 243 respondents, 202 completed the Professional Fulfillment Index portion of the survey. An average score ≥3 on the professional fulfillment section correlates with fulfillment, while an average score ≥1.33 on the burnout section correlates with burnout. The average score of professional fulfillment was 2.17, with 85.6% of respondents reporting lack of professional fulfillment. The average score on burnout was 1, with 40.1% of otolaryngologists reporting burnout. In multivariable analyses, females were found to have statistically lower professional fulfillment (beta = -2.28, P = .010) with higher rates of work exhaustion (beta = 0.62, P < .001), interpersonal disengagement (beta = 2.08, P = .023), and burnout (beta = 4.49, P = .002). Conclusion: Early in the COVID-19 pandemic, most participants reported a lack of professional fulfillment while just under half experienced burnout. Female gender was associated with low professional fulfillment and high work exhaustion, interpersonal disengagement, and burnout. Attention to burnout and job satisfaction during a pandemic is critical for the appropriate well-being of otolaryngology practitioners.

Aroma profile and in-silico molecular docking studies of essential oil against “Aspergillosis” from Eucalyptus polybrachtea

Essential oil from Eucalyptus plant is used as traditional and complementary medicine worldwide. It is used as therapeutic agent in food and pharmaceutical companies due to various biological activities. The objective of present study was aromatic profile of essential oil and molecular docking of Eucalyptus essential oil component eucalyptol (1-8 cineole) against Glucosamine-6-phosphate synthase chitin synthase and UDP-glycosyltransferase, fungal enzymes as an appropriate sites to design drug against “Aspergillosis” and in vitro validation. GC-FID analysis was used to find out aromatic profile. For docking, Patch-dock analysis was used. Ligand Protein 2D and 3D Interactions were also studied. Drug likeliness, toxicity profile and cancer cell line toxicity were also studied. GC-FID profiling revealed the presence of eucalyptol as major bioactive compound, hence selected for further docking studies. Docking analysis indicated effective binding of eucalyptol to Glucosamine-6-phosphate synthase, chitin synthase and UDP-glycosyltransferase. Wet lab validation was performed by two fungal strains Aspergillus niger and Aspergillus oryzae. Molecular docking results indicated that eucalyptol forms tight complexes with Glucosamine-6-phosphate synthase, chitin synthase and UDP-glycosyltransferase enzymes by hydrophobic and hydrogen interactions. Eucalyptol also depicted drug likeliness by LIPINSKY rule, sufficient level of bioactivity, drug likeliness and cancer cell line toxicity. In vitro results revealed that Eucalyptus oil was able to inhibit growth of fungal strains toxicity thus signifying its role as potent anti-fungal drug

Targeting UDP-Glycosyltransferase, Glucosamine-6-Phosphate Synthase and Chitin Synthase by Using Bioactive 1,8 Cineole for “Aspergillosis” Fungal Disease Mutilating COVID-19 Patients: Insights from Molecular Docking, Pharmacokinetics and In-vitro Studies

SARS-CoV-2 (COVID-19)-associated co-infections like “Aspergillosis”, has recently baffled the world. Due to its key role in cell wall synthesis, in the present study UDP-glycosyltransferase, glucosamine-6-phosphate synthase and chitin synthase have been chosen as appropriate targets for molecular docking. The objective of the present study was molecular docking of eucalyptus essential oil component 1,8 cineole against cell wall enzymes followed by in vitro validation. For molecular docking, patch-dock web based online tool was used. Ligand–Protein 2D and 3D Interactions were also studied. Drug likeliness, toxicity profile and cancer cell line toxicity were also studied. Molecular docking results indicated that 1,8 cineole form hydrogen bonding and hydrophobic interactions with UDP-glycosyltransferase, glucosamine-6-phosphate synthase and chitin synthase enzymes. 1,8 cineole also depicted drug likeliness by showing compliance with the LIPINSKY rule, sufficient level of bioactivity and cancer cell line toxicity thus signifying its role as a potent anti-fungal drug.

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.

Objective Assessment of Aerosolization During Transnasal Endoscopy: A Systematic Review.

OBJECTIVE: The goal of this systematic review is to assimilate the literature on objective assessment of particulate aerosolization during transnasal endoscopic procedures. DATA SOURCES: PubMed and hand-searched articles. REVIEW METHODS: The PubMed electronic database was searched using Medical Subject Headings and free-text search terms relating to aerosolization and transnasal endoscopic procedures from inception to November 16, 2020. References were hand-searched to identify additional publications for consideration. Inclusion in the systematic review required quantification of aerosol generation during clinic transnasal endoscopic procedures. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and flowchart were followed during the systematic review. RESULTS: Eight of 900 studies met criteria for inclusion in the systematic review. Five studies tested nasal endoscopy with mixed findings on the risk of aerosol generation during this procedure. Two studies assessed flexible fiberoptic laryngoscopy and also reported mixed findings. Breathing, sneezing, speech, and spray anesthetic/decongestants were found to consistently increase aerosol generation above baseline. A number of studies tested new and general mitigation strategies and were found to be effective in decreasing aerosol generation. CONCLUSIONS: The coronavirus disease 2019 pandemic has informed many considerations regarding patient and provider safety. It is valuable to understand the risk during outpatient otolaryngology procedures through the quantification of aerosolization. There are several effective methods to control aerosolization during these procedures. The findings of this systematic review will inform appropriate precautions to protect against spread of infectious agents by aerosolization.

Managing the supply chain during disruptions: Developing a framework for decision-making

Business-to-business firms have traditionally encountered disruptions, but the scale of the COVID-19 pandemic was extraordinary as it interrupted global supply chains by causing unprecedented shocks to supply and demand. Firms experienced extraordinary pressure and struggled to minimize the immediate and long-term impact of supply chains disruptions. Applying chaos theory, this study employs a single-case method to understand the disruptions to the business-to-business oil and gas supply chain. We make three major contributions. First, we examine firm decision-making during significant disruptions. Second, we use chaos theory to better understand the decision-making process. Finally, we develop a framework to explicate the decision-making process and provide guidelines for decision-making during disruptions. Our findings provide theoretical insights and have important implications for practitioners addressing supply chain disruptions during crises.

Machine Learning Assisted Prediction of Prognostic Biomarkers Associated With COVID-19, Using Clinical and Proteomics Data.

With the availability of COVID-19-related clinical data, healthcare researchers can now explore the potential of computational technologies such as artificial intelligence (AI) and machine learning (ML) to discover biomarkers for accurate detection, early diagnosis, and prognosis for the management of COVID-19. However, the identification of biomarkers associated with survival and deaths remains a major challenge for early prognosis. In the present study, we have evaluated and developed AI-based prediction algorithms for predicting a COVID-19 patient's survival or death based on a publicly available dataset consisting of clinical parameters and protein profile data of hospital-admitted COVID-19 patients. The best classification model based on clinical parameters achieved a maximum accuracy of 89.47% for predicting survival or death of COVID-19 patients, with a sensitivity and specificity of 85.71 and 92.45%, respectively. The classification model based on normalized protein expression values of 45 proteins achieved a maximum accuracy of 89.01% for predicting the survival or death, with a sensitivity and specificity of 92.68 and 86%, respectively. Interestingly, we identified 9 clinical and 45 protein-based putative biomarkers associated with the survival/death of COVID-19 patients. Based on our findings, few clinical features and proteins correlate significantly with the literature and reaffirm their role in the COVID-19 disease progression at the molecular level. The machine learning-based models developed in the present study have the potential to predict the survival chances of COVID-19 positive patients in the early stages of the disease or at the time of hospitalization. However, this has to be verified on a larger cohort of patients before it can be put to actual clinical practice. We have also developed a webserver CovidPrognosis, where clinical information can be uploaded to predict the survival chances of a COVID-19 patient. The webserver is available at http://14.139.62.220/covidprognosis/.

Rapid transition to online teaching program during COVID-19 lockdown: Experience from a medical college of India.

BACKGROUND: COVID-19 pandemic has forced medical colleges around the world to shift to online teaching. There is hardly any evidence regarding such rapid transitions to online teaching, especially from resource-poor settings. We share our experience of developing an online teaching program based on teachers' and students' feedback. MATERIALS AND METHODS: A mixed methods study was conducted during the COVID-19 lockdown period in a public-funded medical institute of India. Online feedback was obtained 3 weeks after the beginning of emergency remote teaching. The responses by the students and teachers shaped the final online teaching program which reinforced the perceived strengths and addressed the weaknesses. Observations were made for the proportion of scheduled lectures delivered through digital platform and students' attendance in the 1st week and last week of the study period. RESULTS: Feedback was obtained from 367 students and 56 teachers. Around three-fourths of the students (76.7%) and teachers (73.2%) were satisfied with online teaching. The themes generated for benefits of online teaching were similar for both students and teachers, but the perceived challenges differed. Students found online teaching more stressful, and teachers were apprehensive of the new technology and lack of a controlled environment. CONCLUSIONS: A rapid transition to development and implementation of an online teaching program was found to be feasible and acceptable to the primary stakeholders. Not only the content but student engagement and supportive environment for both students and teachers are essential requirements in the context of an online undergraduate teaching program.

Rapid telehealth implementation into an otolaryngology practice during the COVID-19 pandemic.

OBJECTIVE: Report outcomes of rapid implementation of telehealth across an academic otolaryngology-head and neck surgery department during the COVID-19 pandemic. METHODS: This is a retrospective, single-institution study of rapid deployment of telehealth during the COVID-19 pandemic. Characteristics of patients were compared between those who agreed and those who declined telehealth care. Reasons for declining telehealth visits were ascertained. Characteristics of telehealth visits were collected and patients were asked to complete a post-visit satisfaction survey. RESULTS: There was a 68% acceptance rate for telehealth visits. In multivariable analysis, patients were more likely to accept telehealth if they were being seen in the facial plastics subspecialty clinic (odds ratio [OR] 59.55, 95% confidence interval [CI] 2.21-1607.52; P = .015) compared to the general otolaryngology clinic. Patients with Medicare (compared to commercial insurance) as their primary insurance were less likely to accept telehealth visits (OR 0.10, 95% CI 0.01-0.77; P = .027). Two hundred and thirty one patients underwent telehealth visits; most visits (69%) were for established patients and residents were involved in 38% of visits. There was an 85% response rate to the post-visit survey. On a scale of one to ten, the median satisfaction score was 10 and 99% of patients gave a score of 8 or higher. Satisfaction scores were higher for new patient visits than established patient visits (P = .020). CONCLUSION: Rapid implementation of telehealth in an academic otolaryngology-head and neck surgery department is feasible. There was high acceptance of and satisfaction scores with telehealth. LEVEL OF EVIDENCE: 3.

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Artificial Intelligence-Based Classification of Chest X-Ray Images into COVID-19 and Other Infectious Diseases.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has led to global health and healthcare crisis, apart from the tremendous socioeconomic effects. One of the significant challenges in this crisis is to identify and monitor the COVID-19 patients quickly and efficiently to facilitate timely decisions for their treatment, monitoring, and management. Research efforts are on to develop less time-consuming methods to replace or to supplement RT-PCR-based methods. The present study is aimed at creating efficient deep learning models, trained with chest X-ray images, for rapid screening of COVID-19 patients. We used publicly available PA chest X-ray images of adult COVID-19 patients for the development of Artificial Intelligence (AI)-based classification models for COVID-19 and other major infectious diseases. To increase the dataset size and develop generalized models, we performed 25 different types of augmentations on the original images. Furthermore, we utilized the transfer learning approach for the training and testing of the classification models. The combination of two best-performing models (each trained on 286 images, rotated through 120° or 140° angle) displayed the highest prediction accuracy for normal, COVID-19, non-COVID-19, pneumonia, and tuberculosis images. AI-based classification models trained through the transfer learning approach can efficiently classify the chest X-ray images representing studied diseases. Our method is more efficient than previously published methods. It is one step ahead towards the implementation of AI-based methods for classification problems in biomedical imaging related to COVID-19.

Subtrochanteric fracture in a near term pregnant female in the back drop of COVID-19 pandemic: A triple trouble pregnant with peril all along

Outbreak of severe acute respiratory syndrome corona virus was first reported in Wuhan province in China. By February all hell broke loose in Europe and other continents. Spread of virus in India with 1.38 billion population posed an unprecedented challenge to its health care system. We hereby report a rare case of subtrochanteric fracture of femur in a near term (35 weeks) pregnant female who was treated at our tertiary care center in the times of Covid-19. Combination of pregnancy and Subtrochanteric femoral fracture is a double trouble with high morbidity and mortality and in time of Corona pandemic it became a unique challenge where two lives were at risk. Here we share our experience of dealing this case with multidisciplinary approach and sticking to our clinical sense as literature for Covid-19 pandemic is barely 4 months old and devoid of any guideline for such cases so far. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences 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.)

Current Paradigms in COVID-19 Research: Proposed Treatment Strategies, Recent Trends and Future Directions.

BACKGROUND: Recent pandemic of coronavirus disease caused by a novel coronavirus SARS-CoV-2 in humans is the third outbreak by this family of viruses leading to an acute respiratory infection, which has been a major cause of morbidity and mortality worldwide.The virus belongs to the genus, Betacoronavirus, which has been recently reported to have significant similarity (>89%) to a severe acute respiratory syndrome (SARS)-related member of the Sarbecoviruses. Current researches are not sufficient to understand the etiological and immunopathobiological parameters related to COVID-19 so as to have a therapeutic solution to the problem. METHODS: A structured search of bibliographic databases for peer-reviewed research literature has been carried out using focused review questions and inclusion/exclusion criteria. Further Standard tools were implied in order to appraise the quality of retrieved papers. The characteristic outcomes of screened research and review articles along with analysis of the interventions and findings of included studies using a conceptual framework have been described employing a deductive qualitative content analysis methodology. RESULTS: This review systematically summarizes the immune-pathobiological characteristics, diagnosis, potential therapeutic options for the treatment and prevention of COVID-19 based on the current published literature and evidence. The current review has covered 125 peerreviewed articles, the majority of which are from high-income technically developed countries providing the most recent updates about the current understanding of the COVID-19 bringing all the significant findings and related researches together at a single platform. In addition, possible therapeutic interventions, treatment strategies and vaccine development initiatives to manage COVID-19 have been proposed. CONCLUSION: It is anticipated that this review would certainly assist the public in general and scientific community in particular to recognize and effectively deal with COVID-19, providing a reference guide for futuristic studies.