Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

A phosphonium ionic liquid conjugated magnetic graphitic carbon nitride nanocomposite: an effective sample pretreatment tool for selenium separation and determination.

We established an innovative and easy-to-use methodology for selenium (Se) extraction and determination from real water samples utilizing a magnetic nanocomposite adsorbent (MNC-SPE) aided by an inductively coupled plasma mass spectrometry (ICP-MS) approach. The MNC-SPE adsorbent was fabricated by hybridizing Fe3O4 nanoparticles on the surface of carbon nitride nanosheets (GCN NSs) that were coated with 1-hexyl-3-methylimidazolium hexafluorophosphate ionic liquid (P-IL). A variety of techniques were used to thoroughly analyze the structural and chemical characteristics of MNC-SPE, and appear to have a great number of diverse active surface functional units (imidazole ring and -NH3+). In order to optimize the key factors affecting the Se extraction, parameters including the adsorbent dosage, contact time, eluent type, eluent volume, eluent time, and reusability of adsorbent were extensively studied. The proposed approach was validated under the optimal reaction conditions, and it showed good linearity between 0.15 and 100 pg µL-1 with a significant R2 value (R2 = 0.9994) toward Se metal. Besides, the Se limit of detection (LOD) and limit of quantification (LOQ) are 0.063 pg µL-1 and 0.147 pg µL-1, respectively. Further, by utilizing tap and river water samples, the applicability of the validated method was tested; the approach showed high Se recovery values in the range of 87.6-115.5% for the spiked real-world samples and the interday and intraday precision (RSD%) values of the approach were 4.8% (n = 6). The MNC-SPE can be regenerated and reused for four consecutive extraction-desorption cycles by employing 0.5 M NaOH eluent.

Molecular Targeting and Novel Therapeutic Approaches against Fungal Infections.

BACKGROUND: Fungal infections have become a worldwide problem due to their involvement in numerous diseases. The risk factors for fungal infections are multiple surgeries, transplant therapies, frequent administration of antibiotics, cancer treatments, and prosthetic devices. The problem of resistance in fungi against drug therapies is widespread, becoming a severe health-related problem. OBJECTIVE: The study's objective was to identify molecular targets that may open new paths for fungal treatment. METHODS: Several research and review articles were studied to gather information regarding the novel mechanism of antifungal drugs. However, identifying novel targets is challenging due to the similarities between host and fungal cells. Although, the plasma membrane and cell wall of fungus offer various drug targets that may target to fight against microbial infections. Unfortunately, biofilm formation and over-expression of protein are a few mechanisms through which fungi develop resistance. RESULTS: Despite these problems, several approaches have been working to prevent and treat fungal infections. Modifying the chemical structure of antifungal drugs may also improve their activity and pharmacokinetics. In this review article, we have discussed the molecular targets and novel techniques to be used for the development of antifungal drugs. In addition, different strategies to overcome resistance in fungi have also been described. CONCLUSION: This article may be helpful for the researchers working on the discovery and development of new antifungal works for resistance to fungal diseases.

Effects of an 18-Week Integrated Yoga Program on Cardiac Autonomic Function in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Cardiotoxicity is a commonly observed adverse effect seen in breast cancer (BC) patients undergoing chemotherapy with attributes toward cardiac autonomic dysfunction (CAD). Yoga, a mind-body system of medicine that has been shown to improve cardiac autonomic nervous system (ANS) activity in various health conditions, could be an effective adjuvant approach in addressing CAD. OBJECTIVE: This study aims to investigate the protective effects of Integrated Yoga Therapy (IYT) on ANS functioning, assessed using Heart rate variability (HRV) in breast cancer patients undergoing chemotherapy. METHODS: A total of 68 (stage I-III) BC patients were randomly assigned into 2 groups: Treatment as Usual group (TAU) and TAU with Yoga Therapy group (TAUYT). All patients underwent anthracycline-based adjuvant chemotherapy for a total of 6 cycles with 21 days/cycle. During chemotherapy, the TAUYT group received IYT 5 days a week for 18 weeks, compared with usual care alone in the TAU group. Resting heart rate (RHR) and HRV, measured in both the time and frequency domains, were used to assess the cardiac ANS function of each patient before and after 6 cycles of chemotherapy. RESULTS: A total of 30 subjects in the TAU group and 29 subjects in the TAUYT group were included in the analysis. At baseline (before chemotherapy), there were no significant differences between the TAU and TAUYT groups in terms of RHR and HRV indices. However, after chemotherapy, patients in the TAU group had a significantly higher average RHR (P < .02) and lower HRV indices with reduced parasympathetic indices: RMSSD (P < .01), pNN50% (P < .04), high-frequency power (P < .001) and increased sympathetic indices: low-frequency power (P < .001) with sympathovagal imbalance: LF/HF (P < .001) compared with patients in the TAUYT group. CONCLUSION: The study showed the protective effects of yoga therapy on CAD in patients receiving anthracycline-based chemotherapy for BC, proposing yoga as a potential adjuvant intervention in improving cardiac health and preventing cardiovascular-related morbidities. TRIAL REGISTRATION: This trial is registered with the Clinical Trials Registry-India (CTRI) database (CTRI/2020/10/028446; October 16, 2020).

Prevention of aspirin-mediated secondary toxicity by combined treatment of carotenoids in macrophages.

Upon understanding the boosting role of carotenoids on the endogenous anti-inflammatory system, it is vital to explore their role in reducing the use of high doses of non-steroidal anti-inflammatory drug (NSAIDs), and their mediated secondary toxicity during the treatment of chronic diseases. The current study investigates the carotenoids potential on inhibition of secondary complications induced by NSAIDs, aspirin (ASA) against lipopolysaccharide (LPS) stimulated inflammation. Initially, this study evaluated a minimal cytotoxic dose of ASA and carotenoids (ß-carotene, BC/lutein, LUT/astaxanthin, AST/fucoxanthin FUCO) in Raw 264.7, U937, and peripheral blood mononuclear cells (PBMCs). In all three cells, carotenoids + ASA treatment reduced the LDH release, NO, and PGE2 efficiently than an equivalent dose of carotenoid or ASA treated alone. Based on cytotoxicity and sensitivity results, RAW 264.7 cells were selected for further cell-based assay. Among carotenoids, FUCO + ASA exhibited an efficient reduction of LDH release, NO, and PGE2 than the other carotenoids (BC + ASA, LUT + ASA, and AST + ASA) treatment. FUCO + ASA combination decreased LPS/ASA induced oxidative stress, pro-inflammatory mediators (iNOS, COX-2, and NF-κB), and cytokines (IL-6, TNF-α, and IL-1ß) efficiently. Further, apoptosis was inhibited by 69.2% in FUCO + ASA, and 46.7% in ASA than LPS treated cells. A drastic decrease in intracellular ROS generation with the increase in GSH was observed in FUCO + ASA compared to LPS/ASA groups. The results documented on the low dose of ASA with a relative physiological concentration of FUCO suggested greater importance for alleviating secondary complications and optimize prolonged chronic disease treatments with NSAID's associated side effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03632-w.

Iron-engineered mesoporous biocarbon composite and its adsorption, activation, and regeneration approach for removal of paracetamol in water.

Three-dimensional multi-porous Iron Oxide/carbon (Fe2O3/C) composites derived from tamarind shell biomass were synthesized by a single-step co-pyrolysis technique and utilized for Paracetamol (PAC) dismissal in the combined adsorption, and advanced oxidation such as electrochemical regeneration techniques. The Fe2O3/C composites were prepared by different pyrolysis temperatures, and named as TS750 (without Fe2O3at 750 °C), MTS450 BCs (Low-450 °C), MTS600 BCs (Moderate-600 °C) and MTS750 BCs (high-750 °C), respectively. As-prepared Fe2O3/C composite was characterized by FE-SEM, XRD, BET, and XPS analysis. The specific surface area and the spatial interaction between the interlayers of Fe2O3 and C were significantly improved by increasing the pyrolysis temperatures from 450 to 750 °C, which improved the adsorption capacity of Fe2O3/C composites in terms of higher rate constants and chemisorption kinetics. The Pseudo-second-order kinetics model fitted in the adsorption test results of Fe2O3/C composites with the highest correlation co-efficiency. The Langmuir-isotherms model fitted in the adsorption test of the TS750 and MTS450 BCs. The Freundlich isotherms model is more fit with MTS600 and MTS750 BCs. Based on the isotherm results, the MTS750 BCs achieved 46.9 mg/g of maximum PAC adsorption capacity. The optimized MTS750 composites could be completely recovered by using an advanced electrochemical oxidation regeneration approach within 180 min. Also, with the adsorption and recovery process, the TOC removal rate improved to ∼79.4%. After the 6th cycle electrochemical oxidation process, the obtained results of the re-adsorption test showed the stabile adsorption activity of the sorbent material. The data outcomes herein propose that this type of combined adsorption and electrochemical approach will be useful in commercial water treatment plants.

Visible fluorescent sensing of Cu2+ ions in urine by reusable chitosan/l-histidine-stabilized silicon nanoparticles integrated thin layer chromatography sheet.

This study reports a facile approach for the fabrication of chitosan (CS, biopolymer)- and l-histidine (L-His, biomolecule)-stabilized self-assembled silicon nanoparticles (SiNPs) for sensing Cu2+ ions. Approached method yielded 3.8 ± 0.04 nm size CS/L-His-SiNPs particles, with high stability against harsh pH and temperature conditions. Besides, CS/L-His-SiNPs highly selective to Copper amongst different metal ions tested (Fe3+, Mg2+, Al3+, Cr3+, Cr6+, Cu2+, Mn2+, Cd2+, Pb2+, Zn2+, Hg2+, Ca2+, Li2+, Po42-, As3+, As5+). As compared to the blank-SiNPs (LOD = 96.49 ± 0.223 µM) and CS-SiNPs (LOD = 33.35 ± 1.004 µM); L-His ligand, enhanced the sensitivity of the CS/L-His-SiNPs toward Cu2+ with remarkable LOD value of 55.02 ± 0.42 nM. Applicability of CS/L-His-SiNPs was evaluated by coating CS/L-His-SiNPs on thin layer chromatography (TLC) sheets, CS/L-His-SiNPs-TLC sheets exhibited significant sensing capacity toward Cu2+ ions, with a detection range of 4.0-900 µM, making them suitable for on-site analysis of Cu2+ ions from both environmental and clinical samples. Finally, Cu2+ sensing practicality of CS/L-His-SiNPs-TLC sheets were challenged against real human urine samples. Expressively, CS/L-His-SiNPs-TLC sheets could be regenerated using ethylenediaminetetraacetic acid (EDTA), without losing their photostability, and can be reused further.

Impact of integrated yoga therapy on cognitive impairment and cardiac dysfunction in relation to quality of life in breast cancer patients undergoing chemotherapy: Study protocol for a two-arm randomized controlled trial.

Background: Chemotherapy-related cognitive impairment (CRCI) and cardiac dysfunction (CRCD) are common adverse effects seen in breast cancer patients undergoing chemotherapy. Even though these effects significantly influence daily functioning and overall quality of life, effective strategies to avoid and/or mitigate these adverse effects remain elusive. Yoga as a Mind-body intervention has been used increasingly by cancer patients and has undergone empirical investigations as a potential intervention for patients with cancer. Furthermore, yoga is associated with improved cognition and cardiac functioning in healthy older adults and subjects with cognitive and cardiac impairments. Accordingly, in the current study, yoga holds promise as an intervention to prevent/manage CRCI and CRCD with improved overall QOL in women receiving chemotherapy for breast cancer. Methods: The study is a two-arm, randomized controlled trial. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy will be recruited from a tertiary care center in Bangalore, India. Following recruitment, subjects are randomized to the intervention group (integrated yoga therapy intervention during chemotherapy) or the control group (standard care during chemotherapy). The study's primary outcome is to measure the quality of life (cognitive domain) using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The other primary objectives will include cognitive functioning using neuropsychological test battery and cardiac autonomic function testing using heart rate variability. Secondary outcomes are Brain-derived neurotrophic factor (BDNF), brain function (functional MRI), Echocardiography, serum cortisol, Functional assessment of cancer therapy-cognition (FACT-Cog V3), perceived stress scale and Ryff Scales of Psychological Well-Being. Assessments take place before, during and after chemotherapy; 16-weeks post chemotherapy and 1-year post-baseline. Discussion: Yoga is a promising intervention for preventing and/or managing chemotherapy-related adverse effects (CRAE) and enhancing the quality of life among breast cancer patients. The findings from this study may also help understand the inner mechanisms involved in the protective and restorative effects of yoga on CRAE and support the use of yoga prophylactically for breast cancer patients. In addition, the results of this study could help chemotherapy-exposed individuals with other solid cancer types who have cognitive and cardiac issues. Ethics and Dissemination: The study is approved by the ethics committee of the HealthCare Global Enterprises Ltd. Hospital (EC/434/19/01) and National Institute of Mental Health and Neurosciences (NIMH/DO/ETHICS SUB-COMMITTEE (BS&NS) 9th MEETING/2018). Clinical Trial Registration: http://ctri.nic.in/Clinicaltrials/advancesearchmain.php, identifier CTRI/2020/10/028446.

A rapid assessment of the impact of coronavirus disease (COVID- 19) pandemic on health care & service delivery for noncommunicable diseases in India.

BACKGROUND AND AIM: The coronavirus disease (COVID-19) pandemic had disrupted the availability, access and utilisation of routine health care services. The present study aimed to assess the impact of COVID-19 pandemic restrictions on India's Non communicable Disease (NCD) health care service delivery. METHODS: The study included existing hospitals in disease registry network of the Indian Council of Medical Research-National Centre for Disease Informatics and Research (ICMR-NCDIR), Bengaluru. The study participants comprised site investigators who were clinicians from many specialities, including general medicine, surgery, cancer, neurology, cardiology, and endocrinology. A standardised questionnaire was prepared to collect data on NCD health care services at the respective hospitals over three months from March to May 2020. RESULTS: Out of 153 hospitals approached for the study, 106 (70%) agreed to participate. Of these, 16 hospitals fully converted for COVID-19 care were excluded from the study. Thus, data from 90 hospitals were included in the final analysis. There had been a total disruption of NCD-related healthcare services during the three months in 44% of the hospitals. In April 2020, the outpatient attendance for over one-third of the hospitals was reduced by more than 75%. Admissions for planned surgeries for cancer treatment were reduced by more than 75% for about 40% of the hospitals. Preventive activities and population-based screening for diabetes, hypertension and cancer appear to have been adversely affected, with about one-third of the hospitals reporting total disruption in April and May 2020. As many as 60% of the institutions reported adequate availability of doctors. Over 91% of the institutions had preparedness/action plans to ensure the continuity of NCD services. CONCLUSION: The study shows that despite adequate human and material resources, NCD outpatient services, elective surgeries and population-based screening were severely affected. Most institutions were prepared to overcome the pandemic-imposed disruption and ensure a continuum of care for NCDs'.

Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium.

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.

Mathematical foundations based statistical modeling of software source code for software system evolution.

Source code is the heart of the software systems; it holds a wealth of knowledge that can be tapped for intelligent software systems and leverage the possibilities of reuse of the software. In this work, exploration revolves around making use of the pattern hidden in various software development processes and artifacts. This module is part of the smart requirements management system that is intended to be built. This system will have multiple modules to make the software requirements management phase more secure from vulnerabilities. Some of the critical challenges bothering the software development community are discussed. The background of Machine Learning approaches and their application in software development practices are explored. Some of the work done around modeling the source code and approaches used for vulnerabilities understanding in software systems are reviewed. Program representation is explored to understand some of the principles that would help in understanding the subject well. Further deeper dive into source code modeling possibilities are explored. Machine learning best practices are explored inline with the software source code modeling.

Treatment of heavy metals containing wastewater using biodegradable adsorbents: A review of mechanism and future trends.

The direct disposal of industrial effluents into the aquatic system is considered as a significant environmental hazard in many countries. Because of poisonous chemicals, substantial volumes of effluent release, as well as the lack of adequate of conventional treatment methodologies, industrial effluent treatment is extremely difficult. Numerous researchers have been interested in adsorption technology for its high efficiency of pollutant removal, low cost, and abundantly available adsorbent. Various adsorbent materials, both natural and modified form, have been widely used for the removal of toxic contaminants from industrial effluent. This paper highlights recent advancements in multiple modification types to functionalize the adsorbent material, resulting in higher adsorption capacity on various toxic pollutants. This review provides an overview of the adsorption mechanism and parameters (pH, adsorbent dosage, initial concentration, temperature and interaction time), which influencing the removal efficiency of adsorbents. Furthermore, this review compiles the desorption study to recover the adsorbent and improve the cycle's financial viability. This review provides a concise overview of the future directions and outlook in the framework of adsorbent application for industrial wastewater treatment.

Green sample pre-treatment technique coupled with UHPLC-MS/MS for the rapid biomonitoring of dietary poly-unsaturated (omega) fatty acids to predict health risks.

Polyunsaturated fatty acids (PUFAs) consumption indicates beneficial effects on cardiovascular disease (CVD) and physiological processes in humans. However, the inappropriate ratio of omega-(ω)-PUFA levels in human blood is considered as raising the risk of CVD. Therefore, monitoring dietary ω-FAs in human serum is vital for early diagnosis for individuals to predict CVD risk. This work reports a fast green sample pre-treatment protocol for sensitive and simultaneous monitoring of ω-3-FAs and ω-6-FAs in serum by novel in-syringe-based ultrasonication-assisted alkaline hydrolysis coupled with vortex-induced liquid-liquid microextraction (IS-USAH-VI-LLME) technique connected with UHPLC-MS/MS analysis. Factors affecting extraction recoveries of ten ω-PUFAs by the presented method were well-studied. ω-3 and ω-6 PUFAs demonstrated excellent linearities between the concentrations between 0.1-10,000 ng mL-1 with good regression coefficients between 0.9910-0.9997. The detection and quantification limits were between 0.05-0.35 and 0.16-1.07 ng mL-1, demonstrating that the presented method is highly sensitive and versatile. The precision of the technique was <8.2% that deemed acceptable in clinical analysis. Further, the proposed method was applied for ω-PUFAs analysis in human blood samples, and spiked recoveries showed between 80.32-119.34% with <9.82% precision. Results proved that the developed method is green, sensitive, and reliable to simultaneously determine ten ω-PUFAs in human blood samples for clinical diagnosis applications for predicting health hazards.

Rapid determination of remdesivir (SARS-CoV-2 drug) in human plasma for therapeutic drug monitoring in COVID-19-Patients.

To tackle the harmful consequences of the widespread COVID-19 pandemic, a broad-spectrum anti-viral drug remdesivir (RDV) has gained the utmost attention recently due to its promising application in treating COVID-19 patients. However, a fast and sensitive analytical methodology is important to monitor RDV drug profile in human plasma for pharmacokinetics (PK) and therapeutic drug monitoring (TDM). In this study, we demonstrate an improved vortex-assisted salt-induced liquid-liquid microextraction (VA-SI-LLME) technique coupled with UHPLC-PDA and UHPLC-MS/MS for rapid determination of RDV in human plasma. This technique involves simple one-step protein precipitation with hydrochloric acid and subsequent extraction with acetonitrile for analysis. Under the optimal VA-SI-LLME conditions (500 µL of acetonitrile with 2.5 g ammonium sulfate under 2 min vortex extraction), method validation results indicated an excellent correlation coefficient of 0.9969 for UHPLC-PDA (monitored at 254 nm) and 0.9990 for UHPLC-MS/MS (monitored at electrospray ionization with + ion mode transitions of m/z 603.1→m/z 402.20 and m/z 603.1→ m/z 199.90). The detection and quantification limits were 1.5 and 5 ng/mL for UHPLC/PDA, and 0.3 and 1 ng/mL for UHPLC-MS/MS, respectively. The developed method showed excellent extraction recoveries between 90.79-116.74 % and 85.68-101.34 % with intraday and interday precision ≤ 9.59 for both methods. These results proved that the developed method is a simple, fast, and sensitive analytical method that can be applied as a standard analytical tool for PK and TDM studies of RDV in clinical trials during the current worldwide outbreak.

Software Systems Security Vulnerabilities Management by Exploring the Capabilities of Language Models Using NLP.

Security of the software system is a prime focus area for software development teams. This paper explores some data science methods to build a knowledge management system that can assist the software development team to ensure a secure software system is being developed. Various approaches in this context are explored using data of insurance domain-based software development. These approaches will facilitate an easy understanding of the practical challenges associated with actual-world implementation. This paper also discusses the capabilities of language modeling and its role in the knowledge system. The source code is modeled to build a deep software security analysis model. The proposed model can help software engineers build secure software by assessing the software security during software development time. Extensive experiments show that the proposed models can efficiently explore the software language modeling capabilities to classify software systems' security vulnerabilities.

Low-cost disposable Poly(ethyleneimine)-Functionalized Carbon Nanofibers Coated Cellulose Paper as efficient solid phase extraction sorbent material for the extraction of Parahydroxybenzoates from environmental waters.

Parahydroxybenzoates (parabens) are considered as emerging environmental contaminants because of their extensive usage in our daily life products, causing parabens contamination into environmental water systems and lead to toxic effects on environmental health. This study describes a greener extraction method using a new cationic polymer poly (ethyleneimine) functionalized acid-treated carbon nanofibers (PEI-CNFs) coated cellulose paper (CP) as solid-phase extraction (SPE) sorbent material for the extraction of parabens from environmental water samples. The fabrication of PEI-CNFs modified CP was confirmed using field-emission scanning electron microscope, transmission electron microscopy, and fourier-transformer infrared spectroscopy techniques. Various factors affecting the adsorption and desorption of parabens on PEI-CNFs@CP and its extraction efficiencies were studied using HPLC-UV analysis. Under the optimal experimental conditions, maximum extraction efficiencies were achieved for four target parabens, and PEI-CNFs@CP/HPLC-UV method exhibited excellent linearities ranged from 0.5-50 ng mL-1 with regression coefficient values were between 0.9952-0.9970. The presented method showed good sensitivity with quantification limits between 0.5-0.75 ng mL-1 and detection limits between 0.1-0.25 ng mL-1. The developed technique was applied for the real sample analysis (river, lake, domestic sewage water, and drinking tap water). The spiked recovery revealed good recoveries between 86.8-116.0% with RSD less than 8.8% for all the water samples. These results proved that it a simple, fast, efficient, low-cost, and eco-friendly method for the extraction and determination of parabens in environmental water samples and can be applied as a routine analytical tool in environmental monitoring and quality control laboratories.

Effectiveness of yoga on arterial stiffness: A systematic review.

OBJECTIVES: Arterial stiffness is a major cardiovascular (CV) risk and an independent strong predictor of CV morbidity and mortality. The aim of this systematic review is to evaluate the clinical or interventional studies that assessed the effectiveness of yoga on arterial stiffness in participants of any age or sex, healthy or with any conditions. DESIGN: Systematic review of clinical trials or interventional studies. DATA SOURCES: Cochrane Library, Medline/PubMed, Scopus, and Google Scholar databases. REVIEW METHODS: Databases were searched till July 2019 for clinical trials or interventional studies whether controlled or uncontrolled, randomized or non-randomized studies assessing the effects of yoga on arterial stiffness. Quality of the studies was assessed by using Physiotherapy Evidence Database (PEDro) Scale. RESULTS: Seven full-text articles (total number of participants = 362) that evaluated the effect of yoga on arterial stiffness were included in this review. There were three randomized controlled studies and four were non-controlled studies (single group studies). Four studies have shown significant reduction in arterial stiffness, while three studies did not find any significant change in arterial stiffness. The beneficial effects of yoga intervention on arterial stiffness in young adults and elderly hypertensive patients are encouraging. Methodological quality was good for one study, moderate for two studies and poor for four studies. CONCLUSIONS: This review shows that yoga practice is effective in preventing or reducing the arterial stiffness in young healthy and obese, and elderly hypertensive patients. As the methodology of many studies is of low quality and safety measures were not reported, there is a need of quality randomized controlled trials of yoga effects on arterial stiffness among high risk individuals.