Lipid nanoparticle library towards development next generation genomic medicines

Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.

Computational Insights and Virtual Screening of Repurposed FDA-Approved Drug Against SARS-CoV-2 Protease

In recent times, the emergence of novel Coronavirus and the successive mutations in the viral genome has posed a major threat to public health with strikingly high mortality and morbidity rates across the globe. To address the health concern, the current scenario demands the need for effective therapeutics and at present, the anti-viral drug Remdesivir has been used worldwide to combat the disease. Therefore, in this present study, we have adopted structure-based virtual screening approach to assess the inhibitory potential of the five structural analogues of Remdesivir (Rm) against SARS-CoV-2 main protease (Mpro) using Autodock molecular docking tool. Density functional theory (DFT) calculations have been carried out to gain deep insights into the electronic structure of these analogues. The low HOMO–LUMO gap implies that Rm3 is chemically active and MEP analysis shed light on the possible regions of electronic charge distribution. From the docking results, the analogue compound Rm5 has been identified to exhibit effective inhibitory effect with higher binding affinity (−7.8 kcal mol−1). Most of the docked compounds, however, were found to exhibit good drug-likeness properties and hence could serve as potential candidates against SARS-CoV-2 Corona virus.

ROLE OF GUT MICROBIOME HOMEOSTASIS, INTEGRITY OF THE INTESTINAL EPITHELIAL CELLS, AND THE (ENDOGENOUS) BUTYRATE IN ENDURING A HEALTHY LONG LIFE.

The influence of gut microbiomes on health has been gaining significance lately. More emphasis is their role in neurological illnesses as several of the metabolites and factors produced by the gut affect the brain via the gut-brain axis. Among all the gut microbiome produced metabolites, butyrate has been considered the most significant. Externally supplemented butyrate though has health benefits, when evaluated thoroughly, it is understood that there have been different pathways involved in the production of butyrate by the gut microbiome with the produced butyrate even being detrimental, though majority are beneficial. Importantly maternal butyrate supplementation has resulted in detrimental effects in the offspring. In this background, a black yeast Aureobasidium pullulans produced biological response modifier beta glucans (BRMGs) has shown beneficial outcome (anti-inflammatory: decrease in IL-6, Ferritin, C-reactive protein in COVID-19, D-Dimer; anti-fibrotic in fatty liver disease; improvement of behaviour and sleep with increase in α-synuclein, melatonin in autism) along with its effect on increasing the butyrate producing bacteria in the gut. Since only advantageous outcome has been reported with this BRMG produced butyrate, it is worth being considered as a yardstick for evaluation of exogenously supplemented and endogenous produced butyrate for their differential effects on host and its offspring.

Development of a Novel in-Vitro Hcov-Oc43 Screening Method

Aim: To develop a simple, inexpensive antiviral screening assay, applicable to SARS-CoV-2, using a plate-based bioassay approach to assess the in-vitro activity of compounds against HCoV-OC43. Background(s): Despite the successful deployment of vaccines against SARS-CoV-2 there remains a need for effective antivirals for acute infection treatment. A distinct problem facing the search for new anti-coronavirus compounds is the cost of antiviral screening, compounded by the biosecurity concerns of live SARSCoV- 2 culture. In concert with low pathogenic surrogate virus use, the resazurin reduction assay, which is often employed for compound cytotoxicity assessments can be employed for safe, rapid and inexpensive antiviral screening. Method(s): In-vitro cell based resazurin reduction assays were optimised using remdesivir as a control compound for the assessment of anti-HCoV-OC43 activity. Following optimisation, 246 purified natural compounds from the University of Western Australia's compound collection,were screened using the resazurin bioassay as a primary screen, under pre-treatment and cotreatment conditions. Five compounds, which demonstrated anti- HCoV-OC43 activity, were chosen for secondary screening with dose responses determined using qRT-PCR. Result(s): Primary screens of the 246 compounds using the resazurin bioassay identified five compounds with a relative viral inhibition >60% and a relative cell viability >70% (Table 1). The Z factor of the pre-treatment and co-treatment assays was >0.5 (average +/- SD;0.85 +/- 0.07, 0.91 +/- 0.03 respectively). Further dose response analysis of the top five compounds identified one compound with an IC50 value <10 muM. Conclusion(s): The method developed is an appropriate primary screening tool for the identification of novel compounds with anti-HCoV-OC43 activity.Copyright © 2023 Southern Society for Clinical Investigation.

Tomato Flu/Fever-An analysis of the Hand Foot and Mouth Disease outbreak reported in India

The term "Tomato Flu” or "Tomato Fever” is the colloquial term in India used to describe multiple diseases that present with a fever and rash, with characteristic red, "tomato” shaped blister that appears on different parts of the body, which begin small and increase in size as disease progresses. Some controversy exists on this ‘new viral "flu” that emerged in May 2022 over a period of 2 weeks in areas in the south of India. Currently, local healthcare workers have been encouraged to address the disease as a variant of Hand Foot and Mouth Disease to avoid unnecessary panic on the emergence of a "new outbreak”. With the circulation of other viruses, inadequate testing and poor-quality surveillance in a low resource setting, where healthcare systems are already burdened with ongoing monkeypox outbreak and COVID-19 pandemic, the use of colloquial terms may cause unnecessary panic in the current hypervigilant climate. Confirmation from Government is required to confirm whether this outbreak is due to a mixed infection or a variant of the highly infectious Hand Foot and Mouth Disease virus. © 2022, The authors.

Traditional manipuri cuisine and prospects of promoting medicinal plant-based food tourism in post-COVID-19

In the Post-COVID-19 pandemic, tourists are more health-conscious and look for healthy food during their travel. Food prepared with medicinal plants can be promoted as a tourist product with the competitive advantage of having medicinal properties in the food. From ancient times, Manipuri people have used medicinal plants in their daily food as a food culture of the place. Medicinal plant-based food tourism (MPBFT) can be promoted as a tourism product that can meet the need of post-COVID-19 tourists by offering healthy food with medicinal values and a unique travel experience in Manipur, Northeast India. The main objective of this study is to explore the prospects of promoting MPBFT and focus on identifying the strategies to develop MPBFT in Manipur as a tourism product. This review paper identifies medicinal plants utilized in Manipuri traditional cuisines imparting their medicinal properties. Cultivating medicinal plants, training local communities, organizing educational tours, food festivals, conducting cooking classes, and establishing restaurants focused on Manipuri traditional food with medicinal plants are the strategies to promote Manipur as an MPBFT destination.

Blockchain with Corona Virus: Moving Together to Prevent Future Pandemics

Coronavirus 2 (SARS-CoV-2), which is a severe acute respiratory syndrome, is spreading rapidly all over the world. This disease has been declared a pandemic by the World Health Organization (WHO). The death toll has been increasing due to COVID-19. Global effort is needed to stop the spread of the virus and decrease the death rate. Technically, the death toll is because of improper data management and information sharing. The traditional database system has limitations on tampering with data and collective control systems, especially when data is shared with others. To overcome this problem, “blockchain” technology can be used. It is a distributed ledger technology that acts as a shared database by keeping all the copies verified and synced. This article focuses on blockchain technology and how future pandemics can be prevented using this concept. Blockchain technology can help in preventing pandemics and tracking drug trials, early detection of epidemics, and management of outbreaks and treatment. The containment of outbreaks becomes manageable with easy access to data. It will also be helpful to health authorities. In this chapter, a model is proposed that uses blockchain where each block contains information regarding Covid patients so it becomes easier to track and get the count of infected patients, and data will be secure and can be used for future analysis. © 2022 selection and editorial matter, Vineet Kansal, Raju Ranjan, Sapna Sinha, Rajdev Tiwari, and Nilmini Wickramasinghe;individual chapters, the contributors.

COVID-19 Infection Prediction Using Efficient Machine Learning Techniques Based on Clinical Data

COVID-19 (coronavirus disease) has spread worldwide and has become a pandemic, which causes by the SARS-CoV2 virus. Because the number of cases increases daily, interpreting the laboratory findings takes time, resulting in limitations of findings. Because of these limitations, the need for a clinical decision-making system with predictive algorithms has arisen. By identifying diseases, predictive algorithms would be able to reduce the strain on healthcare systems. In this work, we developed clinical predictive models using machine learning techniques with the help SMOTE+ENN Hybrid technique and laboratory data to develop models that can accurately predict which patients will receive COVID-19. To evaluate our prediction models in this work, precision, F1-score, recall AUC, and Accuracy evaluation metrics are employed. From 600 patients and 10 laboratory findings, the different models are tested and validated with 10-fold cross-validation and holdout cross-validation approaches. The experimental results show that our predictive models can correctly identify patients with COVID-19 with an accuracy of 98.28%, an F1-score of 98.27%, a precision of 98.23%, a recall of 98.32%, and an AUC of 98.32% in the holdout cross-validation approach, and an accuracy of 97.42%, and F1-score of 97.82%, a precision of 97.63%, a recall of 98.05%, and an AUC of 92.66% in 10-fold cross-validation approach. The results of the experiments showed that all machine learning models in the holdout cross-validation approach outperformed the 10-fold cross-validation approach. Finally, to help medical experts with accurately prioritizing resources, predictive models based on laboratory findings have been discovered that can assist in predicting COVID-19 infection and assisting medical professionals to identify which medical resources are most valuable. © 2022 J. Adv. Inf. Technol.

REFLECTIONS OF COVID-19 ON MSMES IN DEVELOPING ECONOMIES: A CASE OF INDIA

The novel coronavirus (COVID-19) has taken the entire global economy into uncertainty and the state of affairs in India is also one and the same. The pandemic crisis has adversely affected all sections of the economy in general and Micro, Small, and Medium Enterprises (MSMEs) in particular. The MSME sector is the nerve centre of all major economies in the world and it plays a vital role in the economic progress of developing countries. It generates huge employment and contributes significantly to the Gross Domestic Product. This paper is a theoretical exposition that aims to review the repercussions of COVID-19 on MSMEs. It also deals with the significance and the developments of MSMEs and the challenges encountered in its progressive path. The role of MSMEs in attaining the Sustainable Development Goals (SDGs) in the developing as well as underdeveloped economies in the wake of COVID-19 is also deliberated. The MSMEs are remarkably contributing to the socio-economic objectives of any country such as job creation, sustainable growth and alleviation of poverty. The chaos caused by covid 19 demanded the revitalizing of the MSMEs with modern technology, market competitiveness and export orientation. Apart from the various governmental measures initiated globally to protect the MSME sector, it is still confronted with multiple problems and requires more stimuli to strengthen it further. © 2022 by Nova Science Publishers, Inc.

COVID-19 AND INDIAN ECONOMY: IMPACT ON MICRO, SMALL AND MEDIUM ENTERPRISES (MSME) SECTOR

The role of MSMEs as a power source of economic growth of the country is highly acknowledged. It plays a notable role in ensuring equitable development in the country. However, most of the small and medium industries which were considered as the backbone of Indian economy are striving hard to keep their business functioning in this lackluster time of crisis. The outbreak of COVID-19 and the subsequent country-wide lockdown made the MSME sector as the worst affected sector. The pandemic-triggered uncertainty around the future flow of income and the declining purchasing power among consumers have endangered the survival of MSMEs. The article mainly focuses on exploring the ramifications of country-wide lockdown due to global pandemic upon the small and medium scale industries of the country. Also, the study tries to connect the listed stock price trends of MSMEs during covid outbreak for analysing the performance of the sector for the period. The analysis shows that the worst economic sentiments are reflected in the price movements of listed small and medium enterprises. It also explores how the stimulus packages declared by central government can revive the sector. The study comes up with a couple of suggestions, such as digitalization, to safeguard and galvanize the sector during this challenging time. © 2022 by Nova Science Publishers, Inc.

VIRTUAL LEARNING IN PSYCHIATRY: A GUIDE FOR EDUCATORS

The global COVID-19 pandemic has had a profound impact on the delivery of undergraduate psychiatry in medical schools across the world. This session will share the key findings on a report jointly produced by the Association of University Teachers of Psychiatry (AUTP) and the World Psychiatric Association (WPA) entitled 'Virtual learning in psychiatry: a guide for educators'. The session will be an interactive session that will provide undergraduate medical educators with an experiential update on delivering undergraduate psychiatry teaching virtually. At the end of the session, delegates will learn how to: •• Promote asynchronous learning through the use of artificial intelligence, online webinars, media and films. •• Deliver synchronous learning through the use of virtual ward rounds and virtual outpatient clinics, use of virtual expert patient sessions, teaching in specific psychiatric settings (e.g. forensic, eating disorders, CAMHS) and online simulation. •• Conduct virtual formative and summative assessments for medical undergraduates. •• Arrange a virtual psychiatry placement for medical undergraduates (including the provision of online Balint groups). •• Maintain a supportive and caring virtual learning environment, with space and time for delivery of the 'hidden curriculum'. •• Recognise the challenges of delivering effective online supervision to medical undergraduates, including international undergraduates.

Human Capital: An Imperative element for Companys Valuation in the Pandemic Era

Human Capital is often one of the most ignored assets, though it plays a very crucial role in deciding the fate of an organization. The Covid-19 pandemic has compelled most companies to change their perceptions towards the importance of their human capital. With increasing acknowledgement about the importance of Human Capital in the pandemic era, many organizations have tried to effectively and efficiently measure their human capital with the help of various parameters. The present research is aimed at investigating the role of competency in the valuation of Human Capital. The current study has been carried out among employees, randomly picked from Information Technology (IT) companies located in Pune city. Primary data was obtained from a sample of 100 respondents for statistical analysis who had sufficient commitment and hands on experience in their domain area. The recent study shows that, companies do put a lot of emphasis on competency assessment while they evaluate their employees in the specific job function that they have been hired to perform. Result obtained verifies that competency assessment played a significantly vital role in the valuation of human capital. © The Electrochemical Society

Preliminary findings on patient satisfaction with telepsychiatry-a systematic review

Introduction: During the COVID-19 pandemic, mental health services have been presented with the unique challenge of providing effective and safe patient care whilst maintaining safety regulations. Telepsychiatry has emerged as a potential solution to this and is now being used across the UK to diagnose and manage mental health conditions. Evidence has shown that its effectiveness is comparable to face to face consultations, however, is much less clear regarding patient satisfaction. We therefore initiated a systematic review to establish whether patients are satisfied with tele-delivery of psychiatric care, and to identify the predictors of a positive experience with telepsychiatry. Methods: A preliminary search was performed using five databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO), with a date restriction between 2010-2020 to reflect advances in technology over the past decade. Results: Preliminary data shows that patient views on telepsychiatric services are largely positive. Factors that arose in literature potentially affecting this include location, cost, privacy, digital literacy and technological issues including audio/video quality. Conclusion: Our study so far shows that patient views on telepsychiatry are generally positive. The review is still in process, however, we anticipate that it will only further support our preliminary findings. These findings will be used to improve patient-centred delivery and provision of telepsychiatric services. We intend to produce a checklist of factors affecting patient satisfaction and test this in a national multicentre study. We are hoping that the study results and the resulting checklist will encourage greater patient involvement in setting up and delivering telepsychiatric services.

The need for exercise sciences and an integrated response to COVID-19: A position statement from the international HL-PIVOT network.

COVID-19 is one of the biggest health crises that the world has seen. Whilst measures to abate transmission and infection are ongoing, there continues to be growing numbers of patients requiring chronic support, which is already putting a strain on health care systems around the world and which may do so for years to come. A legacy of COVID-19 will be a long-term requirement to support patients with dedicated rehabilitation and support services. With many clinical settings characterized by a lack of funding and resources, the need to provide these additional services could overwhelm clinical capacity. This position statement from the Healthy Living for Pandemic Event Protection (HL-PIVOT) Network provides a collaborative blueprint focused on leading research and developing clinical guidelines, bringing together professionals with expertise in clinical services and the exercise sciences to develop the evidence base needed to improve outcomes for patients infected by COVID-19.

Cross-Protection Induced By Encephalitis Vaccines against COVID-19 Might be a Reason for Relatively Lower Mortality Rate in Some Countries

COronaVIrus Disease 2019 (COVID-19) is an on-going pandemic attributed to a novel virus named SARS-CoV-2. Comparing the statistics of incidence and death rates between nations reveals that there is discrepancy amongst countries in these regards, even between countries that share borders. We herein present information from the literature indicating how cross-protection against COVID-19 conferred by the encephalitis vaccine could be the reason for lower fatality rate in the countries where immunization against encephalitis is widespread or included in national programs. This may pave the way for arriving at efficient prevention strategies as well as vaccine development.