Environmental impact of microplastics and potential health hazards.

Microscopic plastic (microplastic) pollutants threaten the earth's biodiversity and ecosystems. As a result of the progressive fragmentation of oversized plastic containers and products or manufacturing in small sizes, microplastics (particles of a diameter of 5 mm with no lower limit) are used in medicines, personal care products, and industry. The incidence of microplastics is found everywhere in the air, marine waters, land, and even food that humans and animals consume. One of the greatest concerns is the permanent damage that is created by plastic waste to our fragile ecosystem. The impossibility of the complete removal of all microplastic contamination from the oceans is one of the principal tasks of our governing body, research scientists, and individuals. Implementing the necessary measures to reduce the levels of plastic consumption is the only way to protect our environment. Cutting off the plastic flow is the key remedy to reducing waste and pollution, and such an approach could show immense significance. This review offers a comprehensive exploration of the various aspects of microplastics, encompassing their composition, types, properties, origins, health risks, and environmental impacts. Furthermore, it delves into strategies for comprehending the dynamics of microplastics within oceanic ecosystems, with a focus on averting their integration into every tier of the food chain.

Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management.

Melatonin, the 'hormone of darkness' is a neuronal hormone secreted by the pineal gland and other extra pineal sites. Responsible for the circadian rhythm and seasonal behaviour of vertebrates and mammals, melatonin is responsible for regulating various physiological conditions and the maintenance of sleep, body weight and the neuronal activities of the ocular sites. With its unique amphiphilic structure, melatonin can cross the cellular barriers and elucidate its activities in the subcellular components, including mitochondria. Melatonin is a potential scavenger of oxygen and nitrogen-reactive species and can directly obliterate the ROS and RNS by a receptor-independent mechanism. It can also regulate the pro- and anti-inflammatory cytokines in various pathological conditions and exhibit therapeutic activities against neurodegenerative, psychiatric disorders and cancer. Melatonin is also found to show its effects on major organs, particularly the brain, liver and heart, and also imparts a role in the modulation of the immune system. Thus, melatonin is a multifaceted candidate with immense therapeutic potential and is still considered an effective supplement on various therapies. This is primarily due to rectification of aberrant circadian rhythm by improvement of sleep quality associated with risk development of neurodegenerative, cognitive, cardiovascular and other metabolic disorders, thereby enhancing the quality of life.

Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.

The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.

Impact of COVID-19 on heart failure hospitalization and outcome in India - A cardiological society of India study (CSI-HF in COVID 19 times study - "The COVID C-HF study").

OBJECTIVES: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. METHODS: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. RESULTS: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. CONCLUSION: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

The Potential Role of Torsemide in Optimizing Loop Diuretic Therapy for Heart Failure Patients.

Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India, torsemide is one of the commonly used loop diuretics for decongestion in heart failure. However, this use of torsemide, including its dosing, and up/down titration, is based on practical experience. Loop diuretic therapy for heart failure patients poses several dilemmas due to the lack of robust evidence based on which treatment decisions can be made. To guide physicians on the optimal use of torsemide in heart failure patients with or without renal impairment, a panel of expert cardiologists and nephrologists from India convened to develop this expert opinion document for the use of torsemide. This expert opinion on torsemide will pave the way for optimal management with loop diuretic therapy in real-world heart failure patients.

A novel benzothiophene incorporated Schiff base acting as a "turn-on" sensor for the selective detection of Serine in organic medium.

A novel fluorogenic sensor N-benzo[b]thiophen-2-yl-methylene-4,5-dimethyl-benzene-1,2-diamine (BTMPD) was synthesized and characterized by using spectroscopic methods including UV-visible, FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The designed fluorescent probe, owing to its remarkable properties, behaves as an efficient turn-on sensor for the sensing of amino acid Serine (Ser). Also, the strength of the probe enhances upon the addition of Ser via charge transfer, and the renowned properties of the fluorophore were duly found. The sensor BTMPD shows incredible execution potential with respect to key performance indicators such as high selectivity, sensitivity, and low detection limit. The concentration change was linear ranging from 5 × 10-8 M to 3 × 10-7 M, which is an indication of the low detection limit of 1.74 ± 0.02 nM under optimal reaction conditions. Interestingly, the Ser addition leads to an increased intensity of the probe at λ = 393 nm which other co-existing species did not. The information about the arrangement and the features of the system and the HOMO-LUMO energy levels was found out theoretically using DFT calculations which is fairly in good agreement with the experimental cyclic voltammetry results. The fluorescence sensing using the synthesized compound BTMPD reveals the practical applicability and its application in real sample analysis.

Pharmacological safety of dimethoxy curcumin-human serum albumin conjugate for potential therapeutic purpose.

Medicinal properties of curcumin are widely published. Previously, researchers used curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its therapeutic value. However, selective conjugation of DMC with human serum albumin (HSA) enhances drug stability and solubility by several folds. Studies using animal models demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo testing, important preclinical data required are toxicological safety and bioavailability of soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution. The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute and sub-acute toxicity, complying with regulatory toxicology. Overall, the study demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a novel study establishing the safety of highly soluble and stable formulation of DMCHSA, qualifying it for intravenous administration and further efficacy evaluation in suitable disease models.

Testing theory of change assumptions of health behavior change interventions: A blended approach exploring local contexts.

This paper used a blended approach that involves multiple techniques to, first, test a set of assumptions around a health behavior change communication intervention theory of change (ToC) and, second, surface some unidentified assumptions involving the local context. The intervention was integrated with women's self-help groups (SHGs) in Uttar Pradesh, India. The key assumption tested in this paper was the linkage between SHG membership, program exposure, and maternal, newborn, and child health practices. Learnings were substantiated through empirical investigations, including structural equation modeling and mediation analysis, as well as 'co-learning' workshops within the community. The workshops aimed to capture and interpret the heterogeneity of local contexts through deep dialogs with the community and program implementers at various levels. Statistical analyses indicated a significant association between the amount of women's program exposure and their health practices. SHG membership was shown to affect maternal health practices; however, it did not have a direct effect on neonatal or child health practices. The 'co-learning' workshops revealed crucial aspects, such as prevailing socio-cultural norms, which prevented pregnant or recently delivered women from participating in SHG meetings. This paper encourages evaluators to work with the community to interpret and co-construct meaning in unpacking the contextual forces that seldom appear in the program ToC.

Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review.

Microfluidics is a revolutionary technology that has promising applications in the biomedical field.Integrating microfluidic technology with the traditional assays unravels the innumerable possibilities for translational biomedical research. Microfluidics has the potential to build up a novel platform for diagnosis and therapy through precise manipulation of fluids and enhanced throughput functions. The developments in microfluidics-based devices for diagnostics have evolved in the last decade and have been established for their rapid, effective, accurate and economic advantages. The efficiency and sensitivity of such devices to detect disease-specific macromolecules like proteins and nucleic acids have made crucial impacts in disease diagnosis. The disease modelling using microfluidic systems provides a more prominent replication of the in vivo microenvironment and can be a better alternative for the existing disease models. These models can replicate critical microphysiology like the dynamic microenvironment, cellular interactions, and biophysical and biochemical cues. Microfluidics also provides a promising system for high throughput drug screening and delivery applications. However, microfluidics-based diagnostics still encounter related challenges in the reliability, real-time monitoring and reproducibility that circumvents this technology from being impacted in the healthcare industry. This review highlights the recent microfluidics developments for modelling and diagnosing common diseases, including cancer, neurological, cardiovascular, respiratory and autoimmune disorders, and its applications in drug development.

HOW did GLP-1RAs bring about a paradigm shift in the guidelines of managing T2DM: A path to gluco-cardio Centricity.

Diabetes is a common condition with a dismal prognosis. According to the International Diabetes Federation, 537 million people worldwide have diabetes. Cardiovascular disorders (CVD) are the major cause of death globally. Diabetes mellitus type 2 (T2DM) increases the risk of CVD. Since 2008, the FDA has required all new antihyperglycemic treatments to show no increased CV risk. Years of glucocentric diabetic therapy have left many patients on medicines with no known CV benefit. GLP-1 receptor agonists (GLP-1RAs) are excellent glucose-lowering medicines with little risk of hypoglycaemia, CVD and weight loss. GLP-1RAs may also delay renal disease development. As an adjunct to metformin or ongoing therapy, GLP1RAs or sodium-glucose cotransporter-2 inhibitors are recommended by the American Diabetes Association and the European Association for the Study of Diabetes (EASD). Thus, this review summarises GLP-1RA and their significance in the paradigm shift in diabetes care recommendations from glucocentric to gluco-cardiocentric.

Crystal structure, DFT studies, Hirshfeld surface and energy framework analysis of 4-(5-nitro-thiophen-2-yl)-pyrrolo [1, 2-a] quinoxaline: A potential SARS-CoV-2 main protease inhibitor.

The title compound 4-(5-nitro-thiophen-2-yl)-pyrrolo[1,2-a] quinoxaline (5NO2TAAPP) was obtained by a straightforward catalyst-free reaction of 5-nitro-2- thiophene carboxaldehyde and 1-(2-aminophenyl) pyrrole in methanol and was structurally characterized by FT IR, UV-Vis, NMR spectroscopic techniques and elemental analysis. The structure of the compound has been confirmed by the single-crystal X-ray diffraction technique. The compound crystallizes in a monoclinic crystal system with space group P21/c. Unit cell dimensions: a = 12.2009(17) A0, b = 8.3544(9) A0, c = 13.9179(17) A0 and ß = 104.980(5) A0. Hirshfeld surface analysis was carried out to understand the different intermolecular interactions. The two-dimensional fingerprint plot revealed the most prominent interactions in the compound. Theoretical calculations were executed using Density functional theory (DFT) by Gaussian09 software to develop optimized geometry and frontier molecular orbital analysis. Molecular docking studies revealed that the title compound is a potent inhibitor of Main protease 3CLpro with PDB ID: 6LU7, the viral protease which is responsible for the new Corona Virus Disease (COVID-19).

Heart Failure with Preserved Ejection Fraction: Management Guidelines (From Heart Failure Association of India, Endorsed by Association of Physicians of India).

Heart failure with preserved ejection fraction (HFpEF) accounts for 15-20% of patients with heart failure (HF) in India. Diagnosis is by clinical features supported by biomarkers and echocardiography. Lifestyle modifications, control of risk factors to optimum levels, and treatment of comorbidities are essential in the management of HFpEF. Spironolactone and sacubitril-valsartan [angiotensin receptor neprilysin inhibitor (ARNI)] are beneficial in subsets of HFpEF, especially with lower range of ejection fraction (EF). Sodium-glucose co-transporter-2 inhibitors (SGLT2i)-empagliflozin and dapagliflozin and probably sotagliflozin are the only currently available drugs which have shown benefits in HFpEF, mostly by reducing hospitalizations. The benefit of SGLT2i is evident in both diabetic and nondiabetic subsets.

Pharmacogenetic variants influence vitamin K anticoagulant dosing in patients with mechanical prosthetic heart valves.

Background: Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of VKORC1, CYP2C9 and CYP4F2 genotypes in predicting VKA dosing. Materials & methods: A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. Results: The VKORC1 rs9923231, CYP2C9*3 and CYP4F2*3 mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. Conclusion: These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.

Clinical characteristics and 30-day outcomes in patients with acute decompensated heart failure: Results from Indian College of Cardiology National Heart Failure Registry (ICCNHFR).

BACKGROUND: Acute decompensated heart failure (ADHF) is a challenging medical emergency with high mortality and its prevalence is increasing in India. There is paucity of data on ADHF in the country. METHODS: Indian College of Cardiology National Heart Failure Registry (ICCNHFR) is an on-going observational registry on ADHF contributed by 22 hospitals across India; and we present the in-hospital and 30-day outcomes of ADHF patients enrolled from August 2018 to July 2019. Major objective included capturing demographics, comorbid conditions, aetiology, prescription patterns and assessing clinical outcomes. RESULTS: Of 5269 patients (mean age: 61.90 ± 13.85 years) enrolled in this study, males were predominant (67.09%). Mean duration of hospitalization was 5.74 ± 4.74 days. Ischemic heart disease was the most common (75.44%) aetiology. Abnormal electrocardiogram readings were found in most patients (89.86%). LVEF of ˂40% was found in 68.29% of patients. In-hospital mortality rates were 6.98%. The 30-day cumulative mortality was 12.35% and 30-day rehospitalization rate was 7.98%. At discharge, all guideline-based medical therapy (GDMT) were prescribed only to 24.99% of patients and 23.72% adhered to the prescription until 30 days. Older age, high serum creatinine levels and poor LVEF contributed to high mortality and rehospitalization. CONCLUSION: Patients with ADHF were younger and predominantly males. Usage of GDMT in ADHF patients was low (24.99%) and the in-hospital mortality was high. Older age, high serum creatinine levels, poor LVEF contributed for 30-day mortality and rehospitalization. This data on ADHF, could help in developing strategies to improve outcomes for HF patients in India.

Microfluidic synthesis of gelatin nanoparticles conjugated with nitrogen-doped carbon dots and associated cellular response on A549 cells.

Gelatin nanoparticles are a versatile class of nanoparticles with wide applications, especially in drug delivery and gene delivery. The inherent biocompatible nature of gelatin and various functional groups can improve the cellular interactions and enhance the efficacy of different drug formulations. Microfluidic hydrodynamic flow-focusing techniques can be used for the synthesis of gelatin nanoparticles. The present work syntheses nitrogen-doped carbon dots conjugated with gelatin nanoparticles (NQD-GNPs) using a microfluidic approach and associated cellular response through various assays. MTT, neutral red uptake, and Calcein AM/Propidium iodide (PI) assays independently proved the biocompatible nature of NQD-GNPs. The NQD-GNPs treatment demonstrated a slight increase in reactive nitrogen species generation and lactate dehydrogenase release. However, it does not alter the mitochondrial membrane potential or lysosomal stability. The cellular uptake of NQD-GNP depends on the concentration and does not affect the apoptotic pathway of the cells. Most of the cells remained viable even after treatment with high concentrations of NQD-GNPs.

Comprehensive Development in Organ-On-A-Chip Technology.

The expeditious advancement in the organ on chip technology provided a phase change to the conventional in vitro tests used to evaluate absorption, distribution, metabolism, excretion (ADME) studies and toxicity assessments. The demand for an accurate predictive model for assessing toxicity and reducing the potential risk factors became the prime area of any drug delivery process. Researchers around the globe are welcoming the incorporation of organ-on-a-chips for ADME and toxicity evaluation. Organ-on-a-chip (OOC) is an interdisciplinary technology that evolved as a contemporary in vitro model for the pharmacokinetics and pharmacodynamics (PK-PD) studies of a proposed drug candidate in the pre-clinical phases of drug development. The OOC provides a platform that mimics the physiological functions occurring in the human body. The precise flow control systems and the rapid sample processing makes OOC more advanced than the conventional two-dimensional (2D) culture systems. The integration of various organs as in the multi organs-on-a-chip provides more significant ideas about the time and dose dependant effects occurring in the body when a new drug molecule is administered as part of the pre-clinical times. This review outlines the comprehensive development in the organ-on-a-chip technology, various OOC models and its drug development applications, toxicity evaluation and efficacy studies.

Intracellular inflammatory signalling cascades in human monocytic cells on challenge with phytohemagglutinin and 2,4,6-trinitrophenol.

Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.