Analytical method development and validation for simultaneous estimation of Bempedoic acid and Ezetimibe in pure and its pharmaceutical dosage form by RP-HPLC.

A simple, accurate and precise method was developed for the simultaneous estimation of the bempedoic acid and ezetimibe in pure and tablet dosage form. The developed method was validated as per International Conference on Harmonization guidelines. The chromatographic separation was achieved isocratically on a Waters- C18, 250 × 4.6 mm, 5 µm column. Mobile phase containing K2HPO4-methanol in the ratio 60:40 in buffer at pH 4.3 was pumped through column at a flow rate of 1.0 ml/min. The temperature was maintained at 25°C. The optimized wavelength selected was 242 nm. The separation of bempedoic acid and ezetimibe showed retention times of 3.090 and 4.268 min respectively. The RSD values of the bempedoic acid and ezetimibe were 0.34 and 0.08 respectively. The accuracy of method was determined at three levels (50,100 and 150%). The percentage recovery was obtained as 100.0 and 100.0% for bempedoic acid and ezetimibe, respectively. The limits of determination and quantitation obtained from regression equations of bempedoic acid and ezetimibe were 1.065, 3.550 and 0.203, 0.677, respectively. The regression equation of bempedoic acid is y = 20,795x + 24,168, and it is y = 6,885.7x + 11,000 for ezetimibe. The retention times were decreased and the run time was decreased, so that the method developed is simple and economical that can be adopted for regular quality control tests in industry.

Quality of life and associating factors in pulmonary tuberculosis patients.

BACKGROUND: Quality of life is a significant issue among patients with tuberculosis and is used for evaluating treatment responses and therapeutic outcome. This study aimed to assess the quality of life in tuberculosis patients receiving anti-tuberculosis therapy for a short duration in the Vellore district of Tamil Nadu and its associated variables. METHODS: A cross-sectional study was designed to evaluate pulmonary tuberculosis patients receiving treatment under category -1 registered in the NIKSHAY portal at Vellore. A total of 165 pulmonary tuberculosis patients were recruited from March 2021 to the third week of June 2021. On obtaining informed consent, the data were collected through the telephone interview by administering WHOQOL- BREF structured questionnaire. The data were examined with descriptive and analytical statistics. Multiple regression analysis for independent quality of life variables was done. RESULTS: The lowest median scores, 31(25,38) & 38(25,44) was, related to psychological and environmental domains, respectively. In addition, the Man-Whitney & Kruskal Wallis showed a statistically significant variation in the mean quality of life for gender, employment status, duration of treatment, persistent symptoms, the location of residence of patients, and the stage of therapy. Age, gender, marital status, and persistent symptoms were the main associating factor. CONCLUSION: Tuberculosis and its treatment influence psychological, physical functioning, and the environmental domain of patient quality of life. Attention is required in the follow-up and treatment of patients by monitoring their quality of life.

Prevalence of high-risk HPV among marginalized urban women in India and its implications on vaccination: A cross sectional study.

OBJECTIVE: To discover the prevalence and distribution of high-risk human papilloma virus (HPV) subtypes in urban slums and their implications. METHODS: A cross-sectional study was performed to discover prevalence and distribution of high-risk HPV subtypes. We screened 956 women. Data were analyzed using SPSS v.25. Inclusion criterion was married women between 30 and 45 years of age. Exclusion criteria were women with known cervical cancer at the time of the survey or those who had undergone hysterectomy. RESULTS: Of the women, 32.47% were HPV positive and of these, about 84.50% were positive for high-risk HPV. HPV type 6 (HPV 6) and HPV 11 were not seen in the population. After HPV 16 and HPV 18, type 58 was the most common variant seen in our study. Currently-used vaccines in India do not cover HPV 58. CONCLUSION: Knowing and understanding the distribution of high-risk HPV are necessary for an effective strategy to eliminate cervical cancer from India. Deoxyribonucleic acid-based HPV screening is a useful method along with vaccination to prevent cervical cancer.

A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

Comparative Profiling of Salivary Cortisol and Salivary DHEA-S Among Healthy Pregnant and Non-Pregnant Women.

During pregnancy, circulatory cortisol levels increase, remaining steady over the second-third trimester. In contrast, profile of salivary cortisol during pregnancy is debatable, more influenced by factors like time of sample collection in the day. Circulatory DHEA-S decrease by at least 50% over the second-third trimester of pregnancy. However, profile of salivary DHEA-S is unclear. Objective was to determine changes in salivary cortisol and DHEA-S in healthy pregnant women, compared to non-pregnant women during late morning-early afternoon sampling to avoid fluctuations associated with other times. Pregnant women in their second-third trimester prospectively (n=500) and non-pregnant women (n=133) were enrolled in study with informed consent. Live birth outcome with no pregnancy complications and≥2.5 Kg infant birth weight were included. Concentrations of salivary cortisol and DHEA-S were determined through ELISA assays. Compared to non-pregnant women, pregnant women demonstrated significant increases in salivary cortisol [median (interquartile range)=4.2 (5.1) nmol/l vs. 17.2 (13.9) nmol/l, p<0.001] and salivary DHEA-S median (interquartile range)=2.7 (2.9) nmol/l vs. 3.8 (3.2) nmol/l, p<0.001). Consistently, quartile scores representing higher levels of salivary cortisol and DHEA-S concentrations demonstrated significant association with pregnancy. Quartile scores representing higher salivary cortisol/DHEA-S ratio demonstrated significant association with pregnancy. Study suggests the indicated time range of saliva sampling might best parallel the established profile of circulatory cortisol in pregnant women. However, unlike cortisol, study indicates that the salivary DHEA-S profile is distinct from the well-known profile of circulatory DHEA-S during pregnancy. A combinatorial approach involving both salivary and circulatory compartments could provide comprehensive picture of DHEA-S and hypothalamus-pituitary-adrenal axis during pregnancy.

SARS-CoV-2 Spike Protein Extrapolation for COVID Diagnosis and Vaccine Development.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to coronavirus disease 2019 (COVID-19) pandemic affecting nearly 71.2 million humans in more than 191 countries, with more than 1.6 million mortalities as of 12 December, 2020. The spike glycoprotein (S-protein), anchored onto the virus envelope, is the trimer of S-protein comprised of S1 and S2 domains which interacts with host cell receptors and facilitates virus-cell membrane fusion. The S1 domain comprises of a receptor binding domain (RBD) possessing an N-terminal domain and two subdomains (SD1 and SD2). Certain regions of S-protein of SARS-CoV-2 such as S2 domain and fragment of the RBD remain conserved despite the high selection pressure. These conserved regions of the S-protein are extrapolated as the potential target for developing molecular diagnostic techniques. Further, the S-protein acts as an antigenic target for different serological assay platforms for the diagnosis of COVID-19. Virus-specific IgM and IgG antibodies can be used to detect viral proteins in ELISA and lateral flow immunoassays. The S-protein of SARS-CoV-2 has very high sequence similarity to SARS-CoV-1, and the monoclonal antibodies (mAbs) against SARS-CoV-1 cross-react with S-protein of SARS-CoV-2 and neutralize its activity. Furthermore, in vitro studies have demonstrated that polyclonal antibodies targeted against the RBD of S-protein of SARS-CoV-1 can neutralize SARS-CoV-2 thus inhibiting its infectivity in permissive cell lines. Research on coronaviral S-proteins paves the way for the development of vaccines that may prevent SARS-CoV-2 infection and alleviate the current global coronavirus pandemic. However, specific neutralizing mAbs against SARS-CoV-2 are in clinical development. Therefore, neutralizing antibodies targeting SARS-CoV-2 S-protein are promising specific antiviral therapeutics for pre-and post-exposure prophylaxis and treatment of SARS-CoV-2 infection. We hereby review the approaches taken by researchers across the world to use spike gene and S-glycoprotein for the development of effective diagnostics, vaccines and therapeutics against SARA-CoV-2 infection the COVID-19 pandemic.

Comparative profiling of prenatal cortisol and DHEA-S among pregnant women with poor birth outcome and pregnant women with normal birth outcome.

CONTEXT: Cortisol and dehydroepiandrosterone-sulfate (DHEA-S) are indispensable hormones for normal pregnancy. It is unclear if these hormones, specifically DHEA-S can offer value for predicting poor birth outcome. OBJECTIVE: To compare prenatal cortisol and DHEA-S levels among pregnant women with normal or poor birth outcome. METHODS: Plasma and saliva were collected prospectively from women in second-third trimester of pregnancy. Women with normal birth outcome (NBO) (n = 501) included live birth, no pregnancy complications and ≥2.5 kg infant birth weight. Women with poor birth outcome included adverse birth outcome (ABO) (n = 50) or low birth weight outcome (LBW) (n = 147). Enzyme-linked immunosorbent assay was performed to measure hormone concentrations in plasma and saliva. RESULTS: Circulatory-DHEA-S levels in pregnant women with ABO were higher than women with NBO (p = .043). Among ABO, only stillbirth cases demonstrated significant increase in circulatory-DHEA-S levels (p = .006). Circulatory and salivary cortisol/DHEA-S ratio was lower among women with stillbirth (p = .004) and ABO outcome (p = .043) respectively compared with women with NBO. Consistently, increased odds of ABO were observed in pregnant women with highest circulatory-DHEA-S levels (odds ratio quartile score 1 vs. 4, 2.79, p = .027) and lowest salivary cortisol/DHEA-S ratio (score 4 vs. 2, 2.83, p = .025). Increased odds of stillbirth outcome were observed in pregnant women with highest circulatory-DHEA-S levels (odds ratio quartile score 1 vs. 4, 8.47, p = .046) and lowest circulatory cortisol/DHEA-S ratio (score 4 vs. 1, 4.803, p = .048). Associations remained significant after adjusting for confounders. Women with LBW did not demonstrate significant changes in cortisol or DHEA-S levels. CONCLUSION: Prenatal measurement of DHEA-S or cortisol/DHEA-S ratio may offer significant value for predicting adverse birth, specifically stillbirth outcome.

SARS-CoV-2 infection during pregnancy and pregnancy-related conditions: Concerns, challenges, management and mitigation strategies-a narrative review.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health problem. The SARS-CoV-2 triggers hyper-activation of inflammatory and immune responses resulting in cytokine storm and increased inflammatory responses on several organs like lungs, kidneys, intestine, and placenta. Although SARS-CoV-2 affects individuals of all age groups and physiological statuses, immune-compromised individuals such as pregnant women are considered as a highly vulnerable group. This review aims to raise the concerns of high risk of infection, morbidity and mortality of COVID-19 in pregnant women and provides critical reviews of pathophysiology and pathobiology of how SARS-CoV-2 infection potentially increases the severity and fatality during pregnancy. This article also provides a discussion of current evidence on vertical transmission of SARS-CoV-2 during pregnancy and breastfeeding. Lastly, guidelines on management, treatment, preventive, and mitigation strategies of SARS-CoV-2 infection during pregnancy and pregnancy-related conditions such as delivery and breastfeeding are discussed.

The role of disinfectants and sanitizers during COVID-19 pandemic: advantages and deleterious effects on humans and the environment.

Disinfectants and sanitizers are essential preventive agents against the coronavirus disease 2019 (COVID-19) pandemic; however, the pandemic crisis was marred by undue hype, which led to the indiscriminate use of disinfectants and sanitizers. Despite demonstrating a beneficial role in the control and prevention of COVID-19, there are crucial concerns regarding the large-scale use of disinfectants and sanitizers, including the side effects on human and animal health along with harmful impacts exerted on the environment and ecological balance. This article discusses the roles of disinfectants and sanitizers in the control and prevention of the current pandemic and highlights updated disinfection techniques against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This article provides evidence of the deleterious effects of disinfectants and sanitizers exerted on humans, animals, and the environment as well as suggests mitigation strategies to reduce these effects. Additionally, potential technologies and approaches for the reduction of these effects and the development of safe, affordable, and effective disinfectants are discussed, particularly, eco-friendly technologies using nanotechnology and nanomedicine.

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease-19 (COVID-19): A scoping review.

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS-CoV-2 infection. From the experiences of Novel Coronavirus Disease-19 to date, male patients are likely to suffer from high-intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS-CoV-2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus-derived T lymphocytes) and humoral immunity (antibodies).

Immunotherapies and immunomodulatory approaches in clinical trials - a mini review.

The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.

How artificial intelligence may help the Covid-19 pandemic: Pitfalls and lessons for the future.

The clinical severity, rapid transmission and human losses due to coronavirus disease 2019 (Covid-19) have led the World Health Organization to declare it a pandemic. Traditional epidemiological tools are being significantly complemented by recent innovations especially using artificial intelligence (AI) and machine learning. AI-based model systems could improve pattern recognition of disease spread in populations and predictions of outbreaks in different geographical locations. A variable and a minimal amount of data are available for the signs and symptoms of Covid-19, allowing a composite of maximum likelihood algorithms to be employed to enhance the accuracy of disease diagnosis and to identify potential drugs. AI-based forecasting and predictions are expected to complement traditional approaches by helping public health officials to select better response and preparedness measures against Covid-19 cases. AI-based approaches have helped address the key issues but a significant impact on the global healthcare industry is yet to be achieved. The capability of AI to address the challenges may make it a key player in the operation of healthcare systems in future. Here, we present an overview of the prospective applications of the AI model systems in healthcare settings during the ongoing Covid-19 pandemic.

SARS-CoV-2 infection in farmed minks, associated zoonotic concerns, and importance of the One Health approach during the ongoing COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has now affected over 72.5 million people worldwide, with nearly 1.6 million deaths reported globally as of December 17, 2020. SARS-CoV-2 has been implicated to have originated from bats and pangolins, and its intermediate animal hosts are being investigated. Crossing of the species barrier and exhibition of zoonosis have been reported in SARS-CoV-2 in farm (minks), domesticated (cats and dogs), and wild animals (tigers, puma, and lions). Recently, the rapid spread of SARS-CoV-2 infection was reported in mink farms, which led to the death of a myriad minks. The clinical and pathological findings of SARS-CoV-2 infection and the rapid animal-to-animal transmission in minks are almost similar to the findings observed in patients with COVID-19. Additionally, the rapid virus transmission among minks and the associated mutations resulted in a new mink-associated variant that was identified in both minks and humans, thereby providing evidence of mink-to-human transmission of SARS-CoV-2. The new mink-associated SARS-CoV-2 variant with a possible reduced sensitivity to neutralizing antibodies poses serious risks and is expected to have a direct effect on the diagnostic techniques, therapeutics, and vaccines that are currently under development. This article highlights the current evidence of SARS-CoV-2 infection in farmed minks, and provides an understanding of the pathogenesis of COVID-19 in minks and the associated zoonotic concerns of SARS-CoV-2 transmission from minks to humans with an emphasis on appropriate mitigation measures and on the necessity of adopting the One Health approach during the COVID-19 pandemic.

SARS-CoV-2 existence in sewage and wastewater: A global public health concern?

The SARS-CoV-2/COVID-19 pandemic has spread across the globe and affected millions of individuals as of the efficient virus transmission potential mediated via multiple virus shedding routes. The presence of SARS-CoV-2 in the stool samples and its prolonged shedding in environmental compartments like sewage and wastewater signifies a potential threat adding to the transmission cycle of this novel virus. The potential role played by the asymptomatic COVID-19 patients in transmitting the disease via the fecal-oral route is now under investigation. Hence, in the present scenario, wastewater-based epidemiology, and sewage surveillance may provide valuable insights into the prevalence of SARS-CoV-2 among the human population and could serve as a sensitive surveillance system and a crucial early warning tool. Further studies are required to determine the survival of SARS-CoV-2 in the environment, transmissibility through wastewater, and the potential to infect humans via the fecal-oral route. Appropriate frameworks with regards to evaluation and analysis of SARS-CoV-2 will help implement appropriate intervention strategies and necessary sanitation practices to ensure virus free clean water supply to have a check on the further spread of this pandemic virus.

Plant-based vaccines and antibodies to combat COVID-19: current status and prospects.

Globally, researchers are undertaking significant efforts to design and develop effective vaccines, therapeutics, and antiviral drugs to curb the spread of coronavirus disease 2019 (COVID-19). Plants have been used for the production of vaccines, monoclonal antibodies, immunomodulatory proteins, drugs, and pharmaceuticals via molecular farming/transient expression system and are considered as bioreactors or factories for their bulk production. These biological products are stable, safe, effective, easily available, and affordable. Plant molecular farming could facilitate rapid production of biologics on an industrial scale, and has the potential to fulfill emergency demands, such as in the present situation of the COVID-19 pandemic. This article aims to describe the methodology and basics of plant biopharming, in addition to its prospective applications for developing effective vaccines and antibodies to counter COVID-19.

COVID-19 in the elderly people and advances in vaccination approaches.

The rapid worldwide spread of the COVID-19 pandemic, caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in tens of millions of infections and over one million deaths. SARS-CoV-2 infection affects all age groups; however, those over 60 years old are affected more severely. Moreover, pre-existing co-morbidities result in higher COVID-19-associated mortality in the geriatric population. This article highlights the associated risk factors of SARS-CoV-2 infection in older people and progress in developing COVID-19 vaccines, especially for efficient vaccination of the older population. There is also a summary of immunomodulatory and immunotherapeutic approaches to ameliorate the outcome of COVID-19 in older individuals.

CRISPR-Cas System: An Approach With Potentials for COVID-19 Diagnosis and Therapeutics.

COVID-19, the human coronavirus disease caused by SARS-CoV-2, was reported for the first time in Wuhan, China in late 2019. COVID-19 has no preventive vaccine or proven standard pharmacological treatment, and consequently, the outbreak swiftly became a pandemic affecting more than 215 countries around the world. For the diagnosis of COVID-19, the only reliable diagnostics is a qPCR assay. Among other diagnostic tools, the CRISPR-Cas system is being investigated for rapid and specific diagnosis of COVID-19. The CRISPR-Cas-based methods diagnose the SARS-CoV-2 infections within an hour. Apart from its diagnostic ability, CRISPR-Cas system is also being assessed for antiviral therapy development; however, till date, no CRISPR-based therapy has been approved for human use. The Prophylactic Antiviral CRISPR in huMAN cells (PAC-MAN), which is Cas 13 based strategy, has been developed against coronavirus. Although this strategy has the potential to be developed as a therapeutic modality, it may face significant challenges for approval in human clinical trials. This review is focused on describing potential use and challenges of CRISPR-Cas based approaches for the development of rapid and accurate diagnostic technique and/or a possible therapeutic alternative for combating COVID-19. The assessment of potential risks associated with use of CRISPR will be important for future clinical advancements.

Impact of COVID-19 on women and children and the need for a gendered approach in vaccine development.

The COVID-19 pandemic has imposed unprecedented health and socioeconomic challenges on public health, disrupting it on a global scale. Given that women and children are widely considered the most vulnerable in the times of emergency, whether in war or during a pandemic, the current pandemic has also severely disrupted access to reproductive and child health services. Despite this, data on the effect of the pandemic on pregnant women and newborns remain scarce, and gender-disaggregated indicators of mortality and morbidity are not available. In this context, we suggest the implementation of a gendered approach to ensure the specific needs of women and their newborns are considered during the development of COVID-19 vaccines. Taking into account gender-based biological differences, the inclusion of pregnant and lactating mothers in clinical trials for the development of COVID-19 vaccines is of vital importance.

Geriatric Population During the COVID-19 Pandemic: Problems, Considerations, Exigencies, and Beyond.

The coronavirus disease 2019 (COVID-19) pandemic wreaked havoc worldwide, with more than 20 million confirmed cases and nearly 0. 75 million deaths as of 10th August 2020. Various factors determine the severity and symptoms of this infection. Older age and underlying diseases are the challenges being faced in controlling and treating COVID-19. In 2019, 703 million of the global population was older than 65 years of age. The estimated mortality due to COVID-19 in people older than 76 years of age is reportedly 18%. Frequent infections in older people, higher disease severity, and increased mortality are major challenges in the implementation of appropriate preventive measures and future strategies to protect against this disease in geriatric population. Poor health status, weak immune function, lowered organ function, increased probability of multiple underlying diseases, and poor attention to personal health can increase the susceptibility to various diseases in the geriatric population. Concerning inadequate immunity, the decrease expression of receptors and exaggerated pathophysiologic responses can be debilitating. However, future studies will reveal the hidden facets in these aspects in this COVID-19 catastrophe. In this article, we reviewed the main concerns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the geriatric population, including the risk of acquiring severe COVID-19 resulting in mortality, variation in clinical manifestations, and other pandemic-related concerns. We also discussed the need for increasing attention toward the elderly, taking appropriate prevention and control measures, and considering geriatric-related adjustments in vaccine design and development.