Withania somnifera phytochemicals possess SARS-CoV-2 RdRp and human TMPRSS2 protein binding potential.

Abstract: Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected approximately 26 million people and caused more than 6 million deaths globally. Spike (S)-protein on the outer surface of the virus uses human trans-membrane serine protease-2 (TMPRSS2) to gain entry into the cell. Recent reports indicate that human dipeptidyl peptidase-4 inhibitors (DPP4 or CD26) could also be utilized to check the S-protein mediated viral entry into COVID-19 patients. RNA dependent RNA polymerase (RdRp) is another key virulence protein of SARS-CoV-2 life cycle. The study aimed to identify the potential anti-SARS-CoV-2 inhibitors present in Withania somnifera (Solanaceae) using computer aided drug discovery approach. Molecular docking results showed that flavone glycoside, sugar alcohol, and flavonoid present in W. somnifera showed - 11.69, - 11.61, - 10.1, - 7.71 kcal/mole binding potential against S-protein, CD26, RdRp, and TMPRSS2 proteins. The major standard inhibitors of the targeted proteins (Sitagliptin, VE607, Camostat mesylate, and Remdesivir) showed the - 7.181, - 6.6, - 5.146, and - 7.56 kcal/mole binding potential. Furthermore, the lead phytochemicals and standard inhibitors bound and non-bound RdRp and TMPRSS2 proteins were subjected to molecular dynamics (MD) simulation to study the complex stability and change in protein conformation. The result showed energetically favorable and stable complex formation in terms of RMSD, RMSF, SASA, Rg, and hydrogen bond formation. Drug likeness and physiochemical properties of the test compounds exhibited satisfactory results. Taken together, the present study suggests the presence of potential anti-SARS-CoV-2 phytochemicals in W. somnifera that requires further validation in in vitro and in vivo studies. Supplementary information: The online version contains supplementary material available at 10.1007/s42535-022-00404-4.

Detailed Analysis of Primary Non-invasive Respiratory Support and Outcomes of Subjects With COVID-19 Acute Hypoxaemic Respiratory Failure.

Background The role of non-invasive (continuous positive airway pressure (CPAP) or Non-invasive ventilation (NIV)) respiratory support (NIRS) as a primary oxygenation strategy for COVID-19 patients with acute severe hypoxic respiratory failure (AHRF), as opposed to invasive mechanical ventilation (invasive-MV), is uncertain. While NIRS may prevent complications related to invasive MV, prolonged NIRS and delays in intubation may lead to adverse outcomes. This study was conducted to assess the role of NIRS in COVID-19 hypoxemic respiratory failure and to explore the variables associated with NRIS failure. Methods This is a single-center, observational study of two distinct waves of severe COVID-19 patients admitted to the ICU. Patients initially managed with non-invasive respiratory support with laboratory-confirmed SARS-CoV-2 in acute hypoxaemic respiratory failure were included. Demographics, comorbidities, admission laboratory variables, and ICU admission scores were extracted from electronic health records. Univariate and multiple logistic regression was used to identify predictive factors for invasive mechanical ventilation. Kaplan-Meier survival curves were used to summarise survival between the ventilatory and time-to-intubation groups. Results There were 291 patients, of which 232 were managed with NIRS as an initial ventilation strategy. There was a high incidence of failure (48.7%). Admission APACHE II score, SOFA score, HACOR score, ROX index, and PaO2/FiO2 were all predictive of NIRS failure. Daily (days 1-4) HACOR scores and ROX index measurements highly predicted NIRS failure. Late NIRS failure (>24 hours) was independently associated with increased mortality (44%). Conclusion NIRS is effective as first-line therapy for COVID-19 patients with AHRF. However, failure, particularly delayed failure, is associated with significant mortality. Early prediction of NIRS failure may prevent adverse outcomes.

Development and implementation of a sustainable COVID-19 training package for healthcare workers: Experience from a teaching hospital of North India.

Background: With the impending threat of future COVID-19 waves, it is imperative that teaching hospitals develop, implement, and evaluate a systematic training program to render HCW elastic in delivering COVID-19 related services. We present our experience in developing, implementing, and evaluating a sustainable and scalable COVID-19 patient management training package for healthcare workers. Materials and Methods: A mixed-methods study design was used. Rapid assessment to understand the need of the trainees and identify the available resources was done followed by planning of the training module and its implementation. The program was evaluated for effectiveness and sustainability. Data analysis was done using descriptive statistics and qualitative data generated from open-ended questions in the feedback forms and the discussions were analyzed using rapid content analysis. Results: A total of 66.8% of the doctors and 18.9% of the nurses were trained by online synchronous mode while 55.0% of the nursing officers and 47.1% of the nursing orderlies and paramedical staff were trained in onsite skill development sessions. Need assessment identified that healthcare workers were ill-prepared to use medical devices such as Bipap machines, ventilators, and oxygen delivery devices. The participants mentioned that the multidisciplinary approach and video-based demonstrations facilitated their online learning while the incremental learning approach, easy-to-understand terminology and hands-on experience facilitated their onsite skill development sessions. Conclusion: The COVID-19 training package developed was multidisciplinary, effective, sustainable, and scalable in a resource-limited setting. We suggest that this model can be adapted by healthcare organizations to develop and implement such training packages for their healthcare workers.

Aspergillus in COVID-19 intensive care unit; what is lurking above your head?

Introduction: Through routine respiratory samples surveillance among COVID-19 patients in the intensive care, three patients with aspergillus were identified in a newly opened general intensive care unit during the second wave of the pandemic. Methodology: As no previous cases of aspergillus had occurred since the unit had opened. An urgent multidisciplinary outbreak meeting was held. The possible sources of aspergillus infection were explored. The multidisciplinary approach enabled stakeholders from different skills to discuss possible sources and management strategies. Environmental precipitants like air handling units were considered and the overall clinical practice was reviewed. Settle plates were placed around the unit to identify the source. Reports of recent water leaks were also investigated. Results: Growth of aspergillus on a settle plate was identified the potential source above a nurse's station. This was the site of a historic water leak from the ceiling above, that resolved promptly and was not investigated further. Subsequent investigation above the ceiling tiles found pooling of water and mould due to a slow water leak from a pipe. Conclusion: Water leaks in patient areas should be promptly notified to infection prevention. Detailed investigation to ascertain the actual cause of the leak and ensure any remedial work could be carried out swiftly. Outbreak meetings that include diverse people with various expertises (clinical and non-clinical) can enable prompt identification and resolution of contaminated areas to minimise risk to patients and staff. During challenging pandemic periods hospitals must not lose focus on other clusters and outbreaks occurring simultaneously.

Comparative Effectiveness of Pre-Identified Homeopathic Medicines in Asymptomatic COVID-19 Individuals Receiving Standard Care-An Open-Label, Randomized, Controlled Exploratory Trial.

BACKGROUND: Asymptomatic COVID-19 subjects can transmit the infection for as many as 14 days and are regarded as a significant factor in the rapid spread of the COVID-19 pandemic. This exploratory study aimed to determine any additional benefits of selected homeopathic medicines compared with placebo in asymptomatic COVID-19 individuals receiving standard care. METHODS: This open-label, randomized, placebo-controlled, exploratory trial was undertaken at a COVID Care Centre (CCC) in Madhya Pradesh, India. Patients (n = 200, 18-65 years, both sexes) having a positive RT-PCR and asymptomatic during admission were enrolled. They were randomly assigned to one of four groups (each n = 50): Arsenicum album 30C (Ars. alb.), Camphora 1M (Camph.), Bryonia alba 30C (Bry. alb.) and placebo (Pl.). All the patients were given standard care. The primary outcome was the number of patients becoming RT-PCR negative for SARS-CoV-2 at days 5, 10 and 15. RESULTS: In total, 200 asymptomatic COVID-19 patients were enrolled. One hundred and seventy-seven patients became RT-PCR negative by day 15; 88%, 80%, 98% and 88% from Ars. alb., Camph., Bry. alb. and Pl. respectively. A Chi-square test of association for the total patients who became RT-PCR negative for SARS-Cov-2 in each group showed a marginal statistical significance (Chi-square: 8.1, p = 0.04). A two-proportion Z-test comparing each pre-identified homeopathic medicine with placebo showed marginal statistical significance (p = 0.05) for Bry alb. only. Median time in days to RT-PCR negative (Kaplan Meier analysis) was 10 days in each of the groups. CONCLUSION: There was some evidence that, compared with Ars alb., Camph. or Pl., Bry. alb. was associated with an increased number of patients who became RT-PCR negative for COVID-19 by day 15. The possible effect exerted needs to be investigated in additional research.

Caring for COVID-19 patients through a pandemic in the intensive care setting: A narrative review.

Since the declaration of the novel SARS-CoV-2 virus pandemic, health systems/ health-care-workers globally have been overwhelmed by a vast number of COVID-19 related hospitalizations and intensive care unit (ICU) admissions. During the early stages of the pandemic, the lack of formalized evidence-based guidelines in all aspects of patient management was a significant challenge. Coupled with a lack of effective pharmacotherapies resulted in unsatisfactory outcomes in ICU patients. The anticipated increment in ICU surge capacity was staggering, with almost every ICU worldwide being advised to increase their capacity to allow adequate care provision in response to multiple waves of the pandemic. This increase in surge capacity required advanced planning and reassessments at every stage, taking advantage of experienced gained in combination with emerging evidence. In University Hospital Southampton General Intensive Care Unit (GICU), despite the initial lack of national and international guidance, we enhanced our ICU capacity and developed local guidance on all aspects of care to address the rapid demand from the increasing COVID-19 admissions. The main element of this success was a multidisciplinary team approach intertwined with equipment and infrastructural reorganization. This narrative review provides an insight into the approach adopted by our center to manage patients with COVID-19 critical illness, exploring the initial planning process, including contingency preparations to accommodate (360% capacity increment) and adaptation of our management pathways as more evidence emerged throughout the pandemic to provide the most appropriate levels of care to our patients. We hope our experience will benefit other intensive care units worldwide. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics.

Factors affecting consumer purchase intentions of organic food through fuzzy AHP

Purpose>Organic food market has grown rapidly on a global level and so is the interest of customers. The present paper ranks the factors and sub-criteria which are taken into consideration while making organic purchase decisions resulting in understanding the behaviour of consumers.Design/methodology/approach>The present paper considered a sample of 550 respondents in the area of Punjab. Fuzzy AHP technique was applied to understand the key factors and sub-criteria which play a major role in organic food purchase decisions. The paper is empirical and descriptive in nature. The factors considered for the study include price, consumer knowledge, trust, attitude, behavioural intentions, subjective norms, perceived personal relevance and perceived consumer effectiveness.Findings>The three major influential factors include price, trust and attitude ranked in the same order of preference which majorly affects the purchase decisions and talking about sub-criteria the three major criteria to purchase organic food include: “Price plays a significant role in purchase decisions (P2)”, “Organic food keeps me fit and healthy (A1)” and “Organic food intake makes me feel energetic (A2)”.Research limitations/implications>The present paper is limited to the area of Punjab and majorly eight factors have been taken into consideration. Further research can be explored on broader geographical and cultural areas with new dimensions in criteria and sub-criteria.Practical implications>The findings of this paper will surely help the marketers to understand the behavioural intentions and preferences of the customers. Accordingly, they will strategize the policies to convert organic food market into a niche market with a high growth rate.Originality/value>The existing literature explored various key factors. However, the present study comes up with ranking to the factors according to their priority in purchase decisions. This will definitely help marketers, business houses, practitioners and academicians about the key factors which affect purchase decisions, and it will surely add incredible knowledge into the existing database.

Assessment of the role of the Edinburgh dysphagia score in referral triage in a national service evaluation of the urgent suspected upper gastrointestinal cancer pathway.

BACKGROUND: The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase. AIMS: External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance. METHODS: A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed. RESULTS: 1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss >3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration <6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS. CONCLUSIONS: In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.

Deployment of an Interventional Radiology Telemedicine Program During the COVID-19 Pandemic: Initial Experience With 10,056 Visits.

OBJECTIVE: To evaluate the clinical, operational, and financial effects of using telemedicine services in an academic interventional radiology setting during the coronavirus disease 2019 pandemic and to identify potential barriers to equitable telemedicine access for patients. METHODS: Evaluation and management (E&M) data over a 104-week period from September 2019 to August 2021 were reviewed. Data related to the visits were recorded including visit type, billing provider, patient demographic information, Current Procedural Terminology code charged, and reimbursement received. The ZIP code pertaining to the patient's primary residence was matched with median household income from the US Census Bureau. RESULTS: In all, 14,754 E&M encounters were performed over the study period, of which 10,056 were conducted using telemedicine. Twenty-two percent of visits were performed with interactive video; the remainder were performed using audio only. Female patients were more likely than male patients to use interactive video visits for telemedicine encounters (23.7% versus 20.4%, P < .001). Patients availing of video visits (mean age, 58.1 years, SD = 14.0) were also significantly younger than those patients who used audio-only (telephone) encounters (mean age, 62.5 years, SD = 13.3). Patients with private insurance and those living in neighborhoods with higher median household income were more likely to avail of interactive video visits (P < .001). Professional E&M monthly revenue was between 23.3% and 53.2% of peak prepandemic levels (mean 37.7%). CONCLUSION: Telemedicine services allowed for rapid restoration of E&M encounter volumes over the study period. Further work is required to determine the potential implementation barriers to increasing the use of video visits.

Role of Microalgae in Global CO2 Sequestration: Physiological Mechanism, Recent Development, Challenges, and Future Prospective

The rising concentration of global atmospheric carbon dioxide (CO2) has severely affected our planet’s homeostasis. Efforts are being made worldwide to curb carbon dioxide emissions, but there is still no strategy or technology available to date that is widely accepted. Two basic strategies are employed for reducing CO2 emissions, viz. (i) a decrease in fossil fuel use, and increased use of renewable energy sources;and (ii) carbon sequestration by various biological, chemical, or physical methods. This review has explored microalgae’s role in carbon sequestration, the physiological apparatus, with special emphasis on the carbon concentration mechanism (CCM). A CCM is a specialized mechanism of microalgae. In this process, a sub-cellular organelle known as pyrenoid, containing a high concentration of Ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco), helps in the fixation of CO2. One type of carbon concentration mechanism in Chlamydomonas reinhardtii and the association of pyrenoid tubules with thylakoids membrane is represented through a typical graphical model. Various environmental factors influencing carbon sequestration in microalgae and associated techno-economic challenges are analyzed critically.

National service evaluation of the two week wait upper GI cancer referral pathway

HTU-5 Figure 1The median interval from triage to endoscopy was: 12 days (IQR 8-18) for 2WW;14 days (10-26) for urgent (non-2WW);and 17 days (9-38) for routine endoscopy[Figure omitted. See PDF]ConclusionsTriage based on the BSG recovery guidance was 97% sensitive with a negative predictive value of 99% in diagnosing UGI cancer at 2WW or urgent endoscopy or CT scan. 6.6% of 2WW referrals were safely investigated routinely and over 9% of 2WW referrals required no investigation at all following triage. These findings should guide reform of the upper GI 2WW pathway to reduce the burden on endoscopy during and after the COVID pandemic.

Rhinocerebral Mucormycosis in a COVID-19 Patient from Nepal: A Case Report.

With the surge of cases during the second wave of COVID-19 in Nepal, a number of mucormycosis coinfection cases have also come to our attention. We present a case of a 65-year-old female who was admitted to our emergency department with complaints of pain, swelling, and tingling sensation of the left side of the face along with blood-tinged nasal discharge for 20 days. She had been tested positive for COVID-19 a month back and managed with oxygen support and corticosteroids. Magnetic Resonance Imaging showed invasive fungal sinusitis, with the positive black turbinate sign and mild extension along with the dura mater of the left temporal lobe, and left cavernous sinus. She was diagnosed with rhinocerebral mucormycosis and managed with systemic antifungal therapy and insulin. As per the treatment modality, surgical debridement could not be done because the patient did not give consent.

Mental Health and COVID-19: Challenges and Multimodal Clinical Solutions.

The Coronavirus Disease 2019 (COVID-19) pandemic has led to an exponential rise in mental health issues. Studies have shown that, in times of increased unemployment rates and economic downturn, rates of mental health issues, suicide, substance use, and domestic violence tend to increase. Barriers to care, including stigma and decreased access to providers, contribute to morbidity and mortality. Telehealth services are being utilized to help increase access to care, and economic stimulus packages have been created to help with the financial burden that is often associated with increased mental health stressors. Efforts to prevent burnout and other policy recommendations can help decrease mental health issues in first responders and health care professionals, who are at an increased risk for these problems. Increasing the ability to provide wellness screenings to the general population, to educate the public about preventive measures and practices, and to provide mental health and substance use treatment, such as medication management and therapy services, are among top priorities to further reduce the socioeconomic impact of COVID-19 on mental illness.

Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies.

Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one as lead agents. Compound C1 and C2 showed minimum binding score (-9.08 and -8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (≈ -5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus.Communicated by Ramaswamy H. Sarma.

What Matters to Us: Impact of Telemedicine During the Pandemic in the Care of Patients With Sarcoma Across Scotland.

PURPOSE: In Scotland, approximately 350 sarcoma cases are diagnosed per year and treated in one of the five specialist centers. Many patients are required to travel long distances to access specialist care. The COVID-19 pandemic brought a number of rapid changes into the care for patients with cancer, with increasing utilization of telemedicine. We aimed to evaluate how the utilization of telemedicine affects professionals and patients across Scotland and care delivery, at the Beatson West of Scotland Cancer Centre Sarcoma Unit. METHODS: Between June 8 and August 25, 2020, we invited patients and professional sarcoma multidisciplinary team members to participate in separate online anonymous survey questionnaires, to assess their attitudes toward telemedicine. Data were extracted, and descriptive statistics were performed. RESULTS: Patient satisfaction (n = 64) with telemedicine was high (mean = 9.4/10) and comparable with traditional face-to-face appointments (mean = 9.5/10). Patients were receptive to the use of telemedicine in certain situations, with patients strongly opposed to being told bad news via telemedicine (88%). Providers recommended the use of telemedicine in certain patient populations and reported largely equivalent workloads when compared with traditional consultations. Providers reported that telemedicine should be integrated into regular practice (66%), with patients echoing this indicating a preference for a majority of telemedicine appointments (57%). CONCLUSION: Telemedicine in sarcoma care is favorable from both clinician and patient perspectives. Utilization of telemedicine for patients with rare cancers such as sarcomas is an innovative approach to the delivery of care, especially considering the time and financial pressures on patients who often live a distance away from specialist centers. Patients and providers are keen to move toward a more flexible, mixed system of care.

Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study.

Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting Mpro protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ≈ 100) against SARS-Cov-2 Mpro protein. Molecular docking studies revealed that certain W. somnifera compounds exhibit superior binding potential (-6.16 to -12.27 kcal/mol) compared to the standard inhibitors (-2.55 to -6.16 kcal/mol) including nelfinavir and lopinavir. The non-characteristic compounds (quercetin-3-rutinoside-7-glucoside, rutin and isochlorogenic acid B) exhibited higher inhibitory potential in comparison to characteristic W. somnifera compounds withanolide and withanone. Molecular dynamics (MD) simulation studies of the complex for 100 ns confirm favorable and stable binding of the lead molecule. The MMPBSA calculation of the last 10 ns of the protein-ligand complex trajectory exhibited stable binding of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 Mpro. Taken together, the study demonstrates that the non-characteristic compounds present in W. somnifera possess enhanced potential to bind SARS-Cov-2 Mpro active site. We further recommend in vitro and in vivo experimentation to validate the anti-SARS-CoV-2 potential of these lead molecules.

A virtual multi-disciplinary meeting is a cost-effective method of triaging referrals to a regional musculoskeletal oncology service.

BACKGROUND AND AIMS: In 2010, a virtual sarcoma referral model was implemented, which aims to provide a centralised multidisciplinary team (MDT) to provide rapid advice, avoiding unnecessary appointments and providing a streamlined service. The aim of this study is to examine the feasibility of this screening tool in reducing the service burden and expediting patient journey. METHODS AND RESULTS: All referrals made to a single tertiary referral sarcoma unit from January 2010 to December 2018 were extracted from a prospective database. Only 26.0% events discussed required review directly. 30.3% were discharged back to referrer. 16.5% required further investigations. 22.5% required a biopsy prior to review. There was a reduction in the rate of patients reviewed at the sarcoma clinic, and a higher discharge rate from the MDT in 2018 versus 2010 (p < 0.001). This gives a potential cost saving of 670,700 GBP over the 9 year period. CONCLUSION: An MDT meeting which triages referrals is cost-effective at reducing unnecessary referrals. This can limit unnecessary exposure of patients who may have an underlying diagnosis of cancer to a high-risk environment, and reduces burden on services as it copes with increasing demands during the COVID-19 pandemic.