Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.

Assessing the knowledge of medical undergraduates on oral anticoagulation therapy.

Objective: Oral anticoagulant drugs, such as warfarin, are widely used for preventing and treating vascular and thromboembolic disease in patients with chronic atrial fibrillation, venous thrombosis, and coronary heart disease. As oral anticoagulant therapy has such a narrow therapeutic range, complications in administering these drugs can prove to have a detrimental effect on patients such as life-threatening bleeding might occur. It is therefore necessary to have an adequate knowledge about its actions and its interactions with other dietary factors or any other medication involved. This study was therefore formulated in order to evaluate the knowledge as well as to impart proper awareness to the medical undergraduate students about oral anticoagulation therapy such as to prevent any untoward situation that may arise from the process. Methods: A cross-sectional descriptive study was used to assess the knowledge on oral anticoagulant therapy among the medical undergraduates of a tertiary care hospital. A pre-validated structured questionnaire consisting of 28 questions was adopted, and a separate questionnaire was used for each student. Timing of answering the questionnaire was set at 30 minutes. Scores were evaluated such as a correct answer was given a score of one and wrong answer awarded as zero. Adequate knowledge sore was set above 70% and inadequate knowledge at less than 40%. Results: The response rate was found out to be 67.33% with gender distribution observed to be 71% females and 29% males. From the answers evaluated, overall average score of 67.3 ± 15.9 was obtained indicating that most of the respondents have adequate knowledge about the different mechanism, drug-drug interactions, drug-food interactions, and side effects of anticoagulant therapy, and 100% of the students are well aware about the complications and procedures involved to dissipate information about warfarin therapy. Conclusions: Adequate exposure of students to clinical cases will further help them to focus on the importance of anticoagulation and strengthening their knowledge regarding anticoagulant drug therapy. This will influence the process of physician-patient communication for improving anticoagulation outcome.

Role of endoplasmic reticulum stress-related unfolded protein response and its implications in dengue virus infection for biomarker development.

Dengue virus (DENV) causes debilitating disease in humans, which varies at different rates in host cells, such as monocytes, macrophages, dendritic cells, Langerhans cells, and other cell types. Such heterogeneity in DENV infection in cells could be attributed to a range of factors, including host cell immune response, anti-viral cellular proteins, and virus mediated cellular autophagy. This review delineates an important feature of every cell, the unfolded protein response (UPR) that is attributed to the accumulation of several viral and unfolded/misfolded proteins, such as in DENV infection. UPR is a normal process to counteract endoplasmic reticulum (ER) stress that leads to cell autophagy; though the phenomenon is markedly upregulated during DENV infection. This could be attributed to the uncontrolled activation of the key UPR signaling pathways: inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6), which promote cell autophagy under normal and diseased conditions through the downstream regulation of apoptosis promoting factors such as X-box binding protein (XBP1), GADD34, and ATF-6. Because DENV can modulate these signaling cascades, by promoting dysregulated cell autophagy, the ER stress mediated UPR pathways and the inherent agents could play an important role in delineating the severity of dengue infection with a potential for developing DENV targeted therapeutics.

Implications of biosensors and nanobiosensors for the eco-friendly detection of public health and agro-based insecticides: A comprehensive review.

Biosensors, in particular nanobiosensors, have brought a paradigm shift in the detection approaches involved in healthcare, agricultural, and industrial sectors. In accordance with the global expansion in the world population, there has been an increase in the application of specific insecticides for maintaining public health and enhancing agriculture, such as organophosphates, organochlorines, pyrethroids, and carbamates. This has led to the contamination of ground water, besides increasing the chances of biomagnification as most of these insecticides are non-biodegradable. Hence, conventional and more advanced approaches are being devised for the routine monitoring of such insecticides in the environment. This review walks through the implications of biosensors and nanobiosensors, which could offer a wide range of benefits for the detection of the insecticides, quantifying their toxicity status, and versatility in application. Unique eco-friendly nanobiosensors such as microcantilevers, carbon nanotubes, 3D printing organic materials and nylon nano-compounds are some advanced tools that are being employed for the detection of specific insecticides under different conditions. Furthermore, in order to implement a smart agriculture system, nanobiosensors could be integrated into mobile apps and GPS systems for controlling farming in remote areas, which would greatly assist the farmer remotely for crop improvement and maintenance. This review discusses about such tools along with more advanced and eco-friendly approaches that are on the verge of development and could offer a promising alternative for analyte detection in different domains.

Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has been facilitated by the employment of classified big data, in concert with strikingly reinforced computing prowess and cloud storage, across all fields. AI has energized computer-facilitated drug discovery. An unrestricted espousing of machine learning (ML), especially DL, in many scientific specialties, and the technological refinements in computing hardware and software, in concert with various aspects of the problem, sustain this progress. ML algorithms have been extensively engaged for computer-facilitated drug discovery. DL methods, such as artificial neural networks (ANNs) comprising multiple buried processing layers, have of late seen a resurgence due to their capability to power automatic attribute elicitations from the input data, coupled with their ability to obtain nonlinear input-output pertinencies. Such features of DL methods augment classical ML techniques which bank on human-contrived molecular descriptors. A major part of the early reluctance concerning utility of AI in pharmaceutical discovery has begun to melt, thereby advancing medicinal chemistry. AI, along with modern experimental technical knowledge, is anticipated to invigorate the quest for new and improved pharmaceuticals in an expeditious, economical, and increasingly compelling manner. DL-facilitated methods have just initiated kickstarting for some integral issues in drug discovery. Many technological advances, such as "message-passing paradigms", "spatial-symmetry-preserving networks", "hybrid de novo design", and other ingenious ML exemplars, will definitely come to be pervasively widespread and help dissect many of the biggest, and most intriguing inquiries. Open data allocation and model augmentation will exert a decisive hold during the progress of drug discovery employing AI. This review will address the impending utilizations of AI to refine and bolster the drug discovery operation.

Genetic analysis of a Fanconi anemia case revealed the presence of FANCF mutation (exon 1;469>C-T) with implications to develop acute myeloid leukemia.

BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder and one of the most common inherited forms of aplastic anemia. FA is an autosomal recessive or X-linked genetic disorder that is characterized by typical physical malformations and haematopoietic anomalies. In most cases of FA, patients harbor homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~ 10%), FANCD2 (3-6%) or FANCF (2%) genes in different ethnic populations, which leads to inherited bone marrow failure (IBMF). Hence, it is important to screen such mutations in correlation with clinical manifestations of FA in various ethnic populations. APPROACH: An 11 year old female pediatric patient of an East India family was presented with febrile illness, having thrombocytopenia with positive dengue IgM (Immunoglobulin M) and treated as a case of dengue hemorrhagic fever at the initial stage of diagnosis. Chromosomal breakage study was performed based on the abnormal physical examination, which showed 100% breaks, triradials, and quadrilaterals in mitomycin (MMC)-induced peripheral blood lymphocyte culture. Importantly, conventional cytogenetic assay in most of the bone marrow cells revealed an additional gain in chromosome 3q+ [46,XX,add(3)(q25)] and terminal loss in chr8p- [46,XX,del(8)(p23)], which might have a prognostic relevance in the outcomes of the FA patient. The bone marrow aspiration and biopsy were repeated and the results showed acute leukemia with 39% blast cells. Whole-genome sequencing analysis of the patient confirmed the presence of (exon 1; 496 > C-T) non-sense mutation leading to a truncated FANCF protein attributed to a stop codon at the amino acid position 166. CONCLUSION: The study reported the presence of a homozygous C-T exon 1 mutation in FANCF gene in the female pediatric patient from Odisha, India associated with FA. Furthermore, both parents were found to be carriers of FANCF gene mutation, as this allele was found to be in heterozygous state upon genome sequencing. The pathogenicity of the agent was robustly supported by the clinical phenotype and biochemical observations, wherein the patient eventually developed acute myeloid leukemia. The findings of the study infer the importance of early detection of FA and the associated mutations, which might lead to the development of acute myeloid leukemia.

Effects of selenium nanoparticle on the growth performance and nutritional quality in Nile Tilapia, Oreochromis niloticus.

Selenium is an important micronutrient that has antioxidant, growth potential, and reproduction enhancement abilities in various organisms. The aquaculture industry is a significant contributor towards meeting the dietary requirements of a majority of the global population, which further warrants developing novel approaches for enhancing the production of dietary fish. This study was performed to assess the growth performance of Nile tilapia (Oreochromis niloticus) fingerlings (1 gm in average weight and 2.75 cm in average length) upon nano-selenium (Se-Nps) supplementation. Nanoselenium was synthesized using high-energy ball milling (HEBM) using a 10-hour dry milling technique at 10:1 ball-to-powder ratio (BPR), size characterized by XRD and TEM, followed by mixing with basal feed in desired concentrations (0.5 mg/kg, 1 mg/kg, and 2 mg/kg) and administration to Nile tilapia fingerlings for 30 days, followed by the evaluation of growth performance parameters, fatty acid profile analysis using GC-MS, and nutritional quality index (NQI): [Thrombogenicity Index (IT), Atherogenicity Index (IA), n-3/n-6, n-6/n-3)]. Nile tilapia supplemented with 1 mg/kg Se-Nps showed improved growth performance (RGR: 1576.04%, SGR: 4.70%, and FCR: 1.91), demonstrated by higher survivability (> 95%), isometric growth (coefficient of allometry, b = 2.81), and higher weight gain compared to control (RGR: 680.41%, SGR: 3.42%, and FCR: 1.31), 0.5 mg/kg Se-Nps (RGR: 770.83%, SGR: 3.61%, and FCR: 1.18) and 2 mg/kg Se-Nps (RGR: 383.67%, SGR: 2.63%, and FCR: 1.22). The average length-weight relationship assessed as the condition factor (K) was highest in the 1 mg/kg Se-Nps group compared to others (p < 0.05). GC-MS analysis revealed that Nile tilapia supplemented with 1 mg/kg Se-Nps showed better meat quality, higher amount of n-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, high PUFA/SAFA ratios (1.35) and n-3/n-6 (0.33) ratios, with low atherogenicity index (0.36) and thrombogenic index (0.44), and relatively low n-6/n-3 fatty acid ratio (3.00) compared to other groups. Overall, Se-Nps supplementation at 1 mg/kg enhanced the growth performance and meat quality in Nile tilapia, and therefore could be a potential growth-promoting micronutrient for aquaculture enhancement.

Identification of a novel homozygous intron 3 splice site (A>T) mutation in the ARG1 gene in cerebral palsy pediatric cases from Odisha, India.

BACKGROUND: Arginase enzyme is essential for the catalysis of the last step of the urea cycle, resulting in the conversion of L-arginine to L-ornithine and urea. Arginase deficiency could lead to hyperarginemia, an autosomal recessive disorder of the urea cycle that could result in developmental manifestations after the first year of life, followed by gradually progressive atonic cerebral palsy, spastic quadriplegia, and mental decline. ARG1 mutations have been reported in hyperarginemia patients of Western countries because they exhibited reduced arginase activity. Hence, it is important to assess ARG1 mutations in cerebral palsy cases with hyperarginemia in different populations. METHODS AND RESULTS: This study involved two unrelated pediatric patients from two non-consanguineous East Indian families, exhibiting a range of manifestations, including hypotonia of all limbs, mental retardation, and multiple episodes of seizure. The onset of the disease ranged from 1 to 3 years of age. Hyperammonemia (> 250 micromoles) and serum hyperarginemia (> 350 micromoles) were observed in both the patients. Whole-genome sequencing, followed by Sanger sequencing of both the patients confirmed the presence of a homozygous 3' splice site variation in intron 3 of the ARG1 gene (chr6: g.131902357A>T) that affects the invariant AG acceptor splice site of exon 4 (c.330-2A>T; ENST00000356962.2). CONCLUSION: The study reported the identification of a novel ARG1 mutation in two different unrelated pediatric cases from Odisha, India associated with hyperarginemia. The pathogenicity of the mutation was robustly supported by the clinical phenotype, complete co-segregation with the disease, and biochemical observations.

Hydoxylated ß- and δ-Hexacholorocyclohexane metabolites infer influential intrinsic atomic pathways interaction to elicit oxidative stress-induced apoptosis for bio-toxicity.

Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to ß-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment.

Prediction of dengue fever outbreaks using climate variability and Markov chain Monte Carlo techniques in a stochastic susceptible-infected-removed model.

The recent increase in the global incidence of dengue fever resulted in over 2.7 million cases in Latin America and many cases in Southeast Asia and has warranted the development and application of early warning systems (EWS) for futuristic outbreak prediction. EWS pertaining to dengue outbreaks is imperative; given the fact that dengue is linked to environmental factors owing to its dominance in the tropics. Prediction is an integral part of EWS, which is dependent on several factors, in particular, climate, geography, and environmental factors. In this study, we explore the role of increased susceptibility to a DENV serotype and climate variability in developing novel predictive models by analyzing RT-PCR and DENV-IgM confirmed cases in Singapore and Honduras, which reported high dengue incidence in 2019 and 2020, respectively. A random-sampling-based susceptible-infected-removed (SIR) model was used to obtain estimates of the susceptible fraction for modeling the dengue epidemic, in addition to the Bayesian Markov Chain Monte Carlo (MCMC) technique that was used to fit the model to Singapore and Honduras case report data from 2012 to 2020. Regression techniques were used to implement climate variability in two methods: a climate-based model, based on individual climate variables, and a seasonal model, based on trigonometrically varying transmission rates. The seasonal model accounted for 98.5% and 92.8% of the variance in case count in the 2020 Singapore and 2019 Honduras outbreaks, respectively. The climate model accounted for 75.3% and 68.3% of the variance in Singapore and Honduras outbreaks respectively, besides accounting for 75.4% of the variance in the major 2013 Singapore outbreak, 71.5% of the variance in the 2019 Singapore outbreak, and over 70% of the variance in 2015 and 2016 Honduras outbreaks. The seasonal model accounted for 14.2% and 83.1% of the variance in the 2013 and 2019 Singapore outbreaks, respectively, in addition to 91% and 59.5% of the variance in the 2015 and 2016 Honduras outbreaks, respectively. Autocorrelation lag tests showed that the climate model exhibited better prediction dynamics for Singapore outbreaks during the dry season from May to August and in the rainy season from June to October in Honduras. After incorporation of susceptible fractions, the seasonal model exhibited higher accuracy in predicting outbreaks of higher case magnitude, including those of the 2019-2020 dengue epidemic, in comparison to the climate model, which was more accurate in outbreaks of smaller magnitude. Such modeling studies could be further performed in various outbreaks, such as the ongoing COVID-19 pandemic to understand the outbreak dynamics and predict the occurrence of future outbreaks.

Targeting SARS-CoV-2 with Chaga mushroom: An in silico study toward developing a natural antiviral compound.

The novel coronavirus (SARS-CoV-2) has caused large-scale global outbreaks and mainly mediates host cell entry through the interaction of its spike (S) protein with the human angiotensin-converting enzyme-2 (ACE-2) receptor. As there is no effective treatment for SARS-CoV-2 to date, it is imperative to explore the efficacy of new compounds that possess potential antiviral activity. In this study, we assessed the potential binding interaction of the beneficial components of Chaga mushroom, a natural anti-inflammatory and immune booster with that of the SARS-CoV-2 receptor-binding domain (RBD) using molecular docking, MD simulation, and phylogenetic analysis. Beta glycan, betulinic acid, and galactomannan constituents of Chaga mushroom exhibited strong binding interaction (-7.4 to -8.6 kcal/mol) forming multivalent hydrogen and non-polar bonds with the viral S1-carboxy-terminal domain of the RBD. Specifically, the best interacting sites for beta glycan comprised ASN-440, SER 373, TRP-436, ASN-343, and ARG 509 with average binding energy of -8.4 kcal/mol. The best interacting sites of galactomannan included ASN-437, SER 373, TRP-436, ASN-343, and ALA 344 with a mean binding energy of -7.4 kcal/mol; and the best interacting sites of betulinic acid were ASN-437, SER 373, TRP-436, PHE 342, ARG 509, and ALA 344 that strongly interacted with the S-protein (ΔG = -8.1 kcal/mol). The docking results were also compared with an S-protein binding analog, NAG and depicted similar binding affinities compared with that of the ligands (-8.67 kcal/mol). In addition, phylogenetic analysis using global isolates depicted that the current SARS-CoV-2 isolates possessed a furin cleavage site (NSPRRA) in the RBD, which was absent in the previous isolates that indicated increased efficacy of the present virus for enhanced infection through increased interaction with ACE-2. The results showed that Chaga could be an effective natural antiviral that can supplement the current anti-SARS-CoV-2 drugs.

Leading 20 drug-drug interactions, polypharmacy, and analysis of the nature of risk factors due to QT interval prolonging drug use and potentially inappropriate psychotropic use in elderly psychiatry outpatients.

BACKGROUND: Psychotropic medications extend corrected QT (QTc) period in the electrocardiogram (ECG). Psychiatric patients exposed to ⩾1 psychotropic medication(s) represent a group with marked probability of drug-activated QTc-prolongation. Prolonged QTc interval in elderly patients (age > 60 years) is connected to greater risk of all-cause and coronary heart disease deaths. This study aimed at investigating pattern of utilization of QTc-interval protracting medications, QT-extending drug interactions, and prevalence of QTc-interval extending hazard factors in elderly patients. METHODS: This was a cross-sectional, prospective study at the Psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from 1 October 2017 to 30 August 2019 employing the pertinent prescriptions. RESULTS: A total of 832 elderly patients (age 60 years or more) visiting the Psychiatry OPD during the aforementioned study duration were investigated. About 420 (50.5%) patients were males while 412 (49.5%) were females. Of the 832 patients, 588 (70.7%) were using interacting agents with capacity to produce TdP. Almost 1152 interacting torsadogenic medication pairs were unraveled. As per AzCERT/CredibleMeds Classification, 1016 (48.8%), 724 (34.8%), and 248 (12%) agents with potential to interact were identified with 'known', 'possible', and 'conditional risk of TdP', respectively. The common interacting medications belonged to antidepressant (288), proton pump inhibitor (364), antipsychotic (340), antinausea (184), antimicrobial (156), and H2 receptor antagonist (60) therapeutic categories. The all-inclusive frequency of potentially inappropriate psychotropic (PIP) agents administered was 62% (1343/2166) with Beers Criteria 2019, and 46% (997/2166) with STOPP Criteria 2015. CONCLUSION: Many geriatric patients were administered drugs and drug combinations with heightened proclivity toward QT-interval prolongation. Furthermore, reliable evidence-based online drug knowledge resources, such as AzCERT/CredibleMeds Drug Lists, Medscape Drug Interactions Checker, Epocrates Online Interaction Check, and Drugs.com Drug Interactions Checker, can facilitate clinical professionals in selecting drugs for psychiatric patients. A wise choice of medications is imperative to preclude serious adverse sequelae. Therefore, we need to exigently embrace precautionary safety means, be vigilant, and forestall QT-extension and TdP in clinical environments.

Selenium and Zinc Oxide Multinutrient Supplementation Enhanced Growth Performance in Zebra Fish by Modulating Oxidative Stress and Growth-Related Gene Expression.

Selenium and zinc are important dietary micronutrients having antimicrobial and antioxidant roles, thereby assisting in normal development, and an enhanced immune system. Supplementation of selenium and zinc for enhancing the growth performance and reproductive capacity in fish was explored in this study. Selenium nanoparticles (SeNPs) and zinc oxide nanoparticles (ZnONPs) were synthesized by high-energy ball milling (HEBM) using a 10-h dry milling technique at a 10:1 ball-to-powder ratio (BPR) and were premixed with basal feed followed by the administration to adult zebra fish (D. rerio) (2 months old) for 30 days. Growth analysis revealed that zebra fish fed with SeNPs + ZnONPs (2 mg/ kg, equimolar mixture) had significantly higher length and weight than only SeNP (2 mg/ kg) or ZnONP (2 mg/ kg) groups and control zebra fish (p < 0.05). The average length-weight relationships were assessed by estimating the condition factor (C), which was highest in the SeNP + ZnONP group (1.96), followed by a downward trend in SeNP (C = 1.15) and ZnONP (1.11) (p < 0.05). Relative gene expression of growth hormone and insulin-like growth factor-1 was significantly high in the SeNP + ZnONP group compared to other groups (p < 0.05), which indicated that combined administration of both the nanoparticles in basal feed enhanced the growth performance of zebra fish. Intracellular ROS generation was low in the combined group, followed by control, SeNP, and ZnONP groups, indicating higher concentrations of both nanoparticles, in particular, ZnONPs induced oxidative stress. Fecundity and the development of fertilized embryos were significantly high in the SeNP + ZnONP-treated zebra fish compared to only the SeNP- or ZnONP-treated group or control (p < 0.05). These findings indicated that supplementation of SeNP + ZnONP in basal feed could considerably improve the growth performance and development of zebra fish which could be exploited for enhancing aquaculture production.

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models.

Nucleotide-binding oligomerization domain NOD-like receptors (NLRs) are conserved cytosolic pattern recognition receptors (PRRs) that track the intracellular milieu for the existence of infection, disease-causing microbes, as well as metabolic distresses. The NLRP3 inflammasome agglomerates are consequent to sensing a wide spectrum of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Certain members of the NLR family have been documented to lump into multimolecular conglomerates called inflammasomes, which are inherently linked to stimulation of the cysteine protease caspase-1. Following activation, caspase-1 severs the proinflammatory cytokines interleukin (IL)-1ß and IL-18 to their biologically active forms, with consequent commencement of caspase-1-associated pyroptosis. This type of cell death by pyroptosis epitomizes a leading pathway of inflammation. Accumulating scientific documentation has recorded overstimulation of NLRP3 (NOD-like receptor protein 3) inflammasome involvement in a wide array of inflammatory conditions. IL-1ß is an archetypic inflammatory cytokine implicated in multiple types of inflammatory maladies. Approaches to impede IL-1ß's actions are possible, and their therapeutic effects have been clinically demonstrated; nevertheless, such strategies are associated with certain constraints. For instance, treatments that focus on systemically negating IL-1ß (i.e., anakinra, rilonacept, and canakinumab) have been reported to result in an escalated peril of infections. Therefore, given the therapeutic promise of an NLRP3 inhibitor, the concerted escalated venture of the scientific sorority in the advancement of small molecules focusing on direct NLRP3 inflammasome inhibition is quite predictable.

Corrigendum to "Chaga mushroom (Inonotus obliquus) polysaccharides exhibit genoprotective effects in UVB-exposed embryonic zebrafish (Danio rerio) through coordinated expression of DNA repair genes" [Heliyon 7 (2) (February 2021) Article e06003].

[This corrects the article DOI: 10.1016/j.heliyon.2021.e06003.].

Molecular toxicity of Benzo(a)pyrene mediated by elicited oxidative stress infer skeletal deformities and apoptosis in embryonic zebrafish.

Benzo(a)pyrene (BaP) has become an integral component of disposed of plastic waste, organic pollutants, and remnants of combustible materials in the aquatic environment due to their persistent nature. The accumulation and integration of these polycyclic aromatic hydrocarbons (PAHs) have raised concern to human health and ecological safety. This study assessed the BaP-induced in vivo molecular toxicity with embryonic zebrafish inferred by oxidative stress and apoptosis. BaP was found to induce morphological and physiological abnormalities like delayed hatching (p < 0.05). Computational analysis demonstrated the high-affinity interaction of BaP with the zebrafish hatching enzyme (ZHE1) with Arg, Cys, Ala, Tyr, and Phe located at the active site revealing the influence of BaP on delayed hatching due to alteration of the enzyme structure. RT-PCR analysis revealed significant down-regulation of the skeletal genes Sox9a, SPP1/OPN, and Col1a1 (p < 0.05) genes. The cellular investigations unraveled that the toxicity of BaP extends to the skeletal regions of zebrafish (head, backbone, and tail) because of the elicited oxidative stress leading to apoptosis. The study extended the horizon of understanding of BaP toxicity at the molecular level which will enhance the indulgent and designing of techniques for better ecological sustainability.

Parkinson's Disease and Impairment in Mitochondrial Metabolism: A Pathognomic Signature.

Mitochondrial bioenergetics is vital for the proper functioning of cellular compartments. Impairments in mitochondrial DNA encoding the respiratory chain complexes and other assisting proteins, accumulation of intracellular reactive oxygen species, an imbalance in cellular calcium transport, or the presence of organic pollutants, high fat-ketogenic diets or toxins, and advancing age can result in complex disorders, including cancer, metabolic disease, and neurodegenerative disorders. Such manifestations are distinctly exhibited in several age-related neurodegenerative diseases, such as in Parkinson's disease (PD). Defects in complex I along with perturbed signaling pathways is a common manifestation of PD. Impaired oxidative phosphorylation could increase the susceptibility to PD. Therefore, unraveling the mechanisms of mitochondrial complexes in clinical scenarios will assist in developing potential early biomarkers and standard tests for energy failure diagnosis and assist to pave a new path for targeted therapeutics against PD.

Chaga mushroom (Inonotus obliquus) polysaccharides exhibit genoprotective effects in UVB-exposed embryonic zebrafish (Danio rerio) through coordinated expression of DNA repair genes.

Chaga mushroom is one of the promising beneficial mushrooms thriving in the colder parts of Northern hemisphere. Chaga polysaccharides (IOP) have been reported to enhance immune response and alleviate oxidative stress during development. However, the effects of IOP on the genotoxicity in model organisms are yet to be clarified. In this study, IOP was extracted using hot water extraction method, followed by GC analysis. Zebrafish embryos (12 h post fertilization, hpf) were exposed to transient UVB (12 J/m2/s, 305-310nm) for 10 s using a UV hybridisation chamber, followed by IOP treatment (2.5 mg/mL) at 24 hpf for up to 7 days post fertilization (dpf). The genotoxic effects were assessed using acridine orange staining, alkaline comet assay, and qRT-PCR for screening DNA repair genes. Significant reduction in DNA damage and amelioration of the deformed structures in the IOP-treated zebrafish exposed to UVB (p < 0.05) was observed at 5 dpf and thereafter. The relative mRNA expressions of XRCC-5, XRCC-6, RAD51, and GADD45 were significantly upregulated, whereas p53 and BAX were downregulated in IOP-treated UVB-exposed zebrafish compared to UVB-exposed zebrafish. ELISA analysis revealed significantly decreased expression of XRCC5 and RAD51 in UVB-exposed compared to IOP-treated UVB-exposed and control zebrafish (7 dpf). However, p53 and BAX levels were high in UVB-exposed zebrafish, indicating higher apoptosis. Pathway analysis demonstrated coordinated regulation of DNA repair genes; p53 playing a pivotal role in regulating the expression of BAX, thereby promoting apoptosis in UVB-exposed zebrafish. Overall, IOP treatment ameliorated the genotoxic effects in UVB-exposed zebrafish by enhanced expression of DNA repair genes, which assisted in normal development. The study delineated the efficacy of IOP in mitigating UV-induced DNA damage in zebrafish.

Prevalence, severity, and nature of risk factors associated with drug-drug interactions in geriatric patients receiving cancer chemotherapy: A prospective study in a tertiary care teaching hospital.

INTRODUCTION: Polypharmacy increases hazard of drug-drug interactions(DDIs), hospitalization, treatment toxicity, and mortality in elderly individuals with cancer. The present study explores and analyzes prevalence and severity of DDIs in geriatric cancer patients subjected to anticancer chemotherapy, their mechanisms, stratification of severity, and correlation between DDI risk and number of medications taken. METHODS: This was a cross-sectional study conducted between January-July 2019 at the Medical Oncology/Hematology and Radiation-Oncology Departments, All India Institute of Medical Sciences(AIIMS) Rishikesh. The study included a convenience sampling of 126 geriatric cancer patients. RESULTS: 126 patients were enrolled in present study. DDIs were identified in 97.6% of elderly cancer patients, and 88.9% had at least one DDI with antineoplastic medications. Highest number of DDIs involving antineoplastic medications in any given patient was 12. DDIs involving medications used for treatment of non-cancerous diseases were observed in 83.3% of patients; highest number of interactions identified in any given patient was 15. Out of 473 interactions, 237(50.1%) DDIs were attributable to pharmacodynamic mechanisms of action. 126(27%) of DDIs involved pharmacokinetic mechanisms and 110(23.6%) involved unknown mechanisms. In this present study, total number of DDIs could be positively correlated with total number of medications and number of health problems. CONCLUSIONS: Geriatric cancer patients are at high risk of DDIs ascribable to polypharmacy. Physicians may utilize online DDI checking softwares to alert themselves, characterize potential DDIs, and modify medications judiciously. An integrative and algorithmic approach with inclusion of geriatricians, oncologists, cardiologists, general practitioners, and clinical pharmacologists/ pharmacists is imperative to optimize drug therapy.

Quality of life and factors affecting it in adult cancer patients undergoing cancer chemotherapy in a tertiary care hospital.

BACKGROUND: Cancer is the second most common cause of deaths worldwide. Likewise, in India, it is a major health problem, and disease burden is escalating every year. Cancer chemotherapy produces unfavorable effects on the well-being of an individual. Since the past few years, quality of life (QoL) is considered as the main goal of cancer treatment in the survival of a patient. AIM: This current study aimed to assess the QoL and factors affecting it in adult cancer patients undergoing chemotherapy treatment. METHODS AND RESULTS: An analytical, cross-sectional study was conducted to achieve the objectives, employing the consecutive sampling method. A total of 120 adult (>19 years) patients were recruited from daycare chemotherapy unit of a tertiary care hospital. The data were collected using patient record form and Functional Assessment of Cancer Therapy-General (FACT-G), a quality of life (QoL) questionnaire. The overall mean score of quality of life (QoL) was 61.933 ± 5.85502. The domains of functional well-being and emotional well-being were most negatively affected after cancer chemotherapy. Education (illiteracy) and occupation (unemployment) were negatively associated with overall quality of life (QoL) of cancer patients on chemotherapy. Adverse drug reactions due to cancer chemotherapy negatively affect the quality of life (QoL) of cancer patients. Education (illiteracy) affects social well-being domain of cancer patients. Working in the government/private sector has a positive impact on functional well-being domain of quality of life (QoL). CONCLUSION: The study findings suggest an overall low quality of life (QoL) among adult cancer patients undergoing chemotherapy at our setup. It has been identified as a stressful therapy, also affecting both psychological and physical well-being. Poor infrastructure, illiteracy, poverty, and lack of proper treatment facilities at most centres often lead to poor survival outcomes and hence focus has always been on achieving quantity of life rather than quality of life (QoL). This is further complicated due to nonavailability of validated tools in local vernacular, apathy of the treating physicians in the context of QoL aspects and social and cultural factors that are unique to this society. Psycho-oncology needs to become an integral entity of comprehensive cancer care.