Investigation of Levan-Derived Nanoparticles of Dolutegravir: A Promising Approach for the Delivery of Anti-HIV Drug as Milk Admixture.

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.

Fagopyrin F fraction from Fagopyrum tataricum demonstrates photodynamic inactivation of skin infecting bacterium and squamous cell carcinoma (A431) cells.

Photodynamic therapy (PDT) stands out as a noteworthy development as an alternative targeted treatment against skin ailments. While PDT has advanced significantly, research into photo-activatable "Green drugs" derived from plants which are less toxic than the synthetic drugs has not kept pace. This study investigates the potential of Fagopyrin F Containing Fraction (FCF) derived from Fagopyrum tataricum in mediating PDT against Staphylococcus aureus and skin cancer cells (A431). FCF was isolated from the plant extract using thin-layer chromatography, followed by identification of the compound through high-performance liquid chromatography and high-resolution liquid chromatography-mass spectrometry. FCF was tested to determine its antibacterial and anticancer efficacy. Results revealed that FCF-mediated PDT exhibited potent action against S. aureus, significantly reducing bacterial viability (MIC 19.5 µg/100 µL). Moreover, FCF-mediated PDT showed good efficacy against A431 cells, resulting in a notable reduction in cell viability (IC50 29.08 µg/mL). Given the known association between S. aureus and squamous cell carcinoma (SCC), FCF shows the potential to effectively target and eradicate both SCC and the related S. aureus present within the lesions. In silico study reveals that Fagopyrin F effectively binds with the epidermal growth factor (EGFR), one among the highly expressed proteins in the A431 cells, with a binding energy of - 9.6 kcal/mol. The affinity of Fagopyrin F for EGFR on A431 cancer cells along with its cytotoxicity against skin cancer cells while safeguarding the normal cells (L929) plays a major part in the way it targets cancer cells. However, its safety, efficacy, and long-term advantages in treating skin conditions require more investigation, including in vivo investigations and clinical trials.

Phytonano silver for cosmetic formulation- synthesis, characterization, and assessment of antimicrobial and antityrosinase potential.

Novel formulations of silver nanoparticles remain exciting if it is applicable for cosmetic purposes. This study proposes a value-added brand-new nanomaterial for improving skin complexion by inhibiting melanin development. This work aims to develop cost effective, efficient, natural silver nanoparticles phytomediated by aqueous extract of leaf sheath scales of Cocos nucifera (Cn-AgNPs) having potential as tyrosinase inhibitors hindering melanin synthesis. The formation of Cn-AgNPs was assessed spectrophotometrically and confirmed by the sharp SPR spectrum at 425 nm. The chemical composition profiling was characterized by X-ray diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopy. The morphology was confirmed by Field Emission Scanning Electron Microscopy (FESEM) and the thermal stability was assessed by Thermogravimetric analysis (TGA). Pharmacological application studies supported the materialization of Cn-AgNPs with significant antityrosinase potential and considerably improved antibacterial and antioxidant properties. Cn-AgNPs showed potential antibacterial effects against gram-positive and negative strains, including prominent infectious agents of the skin. Antioxidant capacity was confirmed with an IC50 of 57.8 µg/mL by DPPH radical scavenging assay. Furthermore, in vitro melanin content determination was performed using SK-MEL cells. Cell line studies proved that Cn-AgNPs decrease the melanin content of cells. The IC50 value obtained was 84.82 µg/mL. Hence Cn-AgNPs is proposed to be acting as a whitening agent through lessening cellular melanin content and as a significant inhibitor of tyrosinase activity. The antioxidant properties and antibacterial effects can contribute to skin rejuvenation and can prevent skin infections as well. This evidence proposes the development of a new nanostructured pharmaceutical and cosmetic formulation from Cocos nucifera leaf sheath scales.

Bi2WO6 nanoparticles anchored on membrane by grafting via in-situ polymerization for the treatment of antibiotic and pesticides wastewater.

Antibiotics, natural organic matter, and pesticides are detected in the ecosystem's domestic water, surface water, and groundwater and are largely applied in pharmaceuticals and agriculture. Polymeric membranes are effectively remove the various pollutants in the water bodies, but fouling is one of the major limitations of commercial membranes. Herein, we modified the polymeric membrane surface with inorganic photocatalytic nanoparticles. In this work, the hydrothermal method is used for the synthesis of Bi2WO6 nanoparticles and as-synthesized nanoparticles grafted onto the various polymeric membranes, including polyetherimide (PEI), cellulose acetate (CA), polyvinylidene fluoride (PVDF), and polysulfone (PSF). The functional group studies confirmed the existence of nanoparticles and hydroxyl groups on the hybrid membrane. Further, finger-like voids, top-surface morphology, and roughness on the membrane surface were validated via Field Emission Scanning Electron Microscopy (FESEM) and Atomic force microscopy (AFM), respectively. The significant rejection of tetracycline, humic acid, and fulvic acid + atrazine was noted with the synthesized membranes in the following order: PVDF (81.1%, 78.8%, 80.6%) > CA (70.1%, 69.3%, 71.7%) > PSF (72.5%, 73.6%, 67.1%) > PEI (75.9%, 65.5%, 63.7%). The photodegradation efficiency of hybrid membranes against tetracycline, humic acid, and fulvic acid + atrazine was observed in the order: PEI (28.5%, 25.8%, 30.2%) < CA (46.5%, 42.4%, 40.5%) < PSF (46.9%, 37.7%, 44.7%) < PVDF (67.7%, 62.1%, 64.3%). These membranes exhibit an outstanding permeate flux recovery ratio to the neat membrane. Therefore, the grafting of Bi2WO6 nanoparticles creates a potential bonding with PVDF membranes than other polymeric membranes, thus exhibiting an outstanding rejection than hybrid and neat membranes.

Factors related to parental COVID-19 vaccine hesitancy for children: An exploratory factor analysis model.

Introduction: This pandemic has been accompanied by an overabundance of information and misinformation, an 'infodemic' on a global scale which have made acceptability of COVID-19 vaccine a major challenge. The objective of the study was to find out the Beliefs of mothers towards COVID-19 vaccine for children and its impact on vaccine hesitancy. Materials and Methods: After obtaining Institutional ethical clearance and informed consent, a total of 360 mothers who were having at least one child from 5 to 18 years were recruited based on simple random sampling. Face-to-face interview was conducted. The questionnaire was based on the WHO-SAGE working group on vaccine hesitancy. Based on Bartlett's test of sphericity, the model was found to be fit (there is adequate number of correlations for factor analysis) and KMO test results imply the samples are adequate for factor analysis. K means cluster analysis was used to divide the samples into three clusters and individual respondent's cluster membership was also identified. Results: It was found 49.4% of mothers were hesitant to vaccine their children against COVID-19. The seven items (reasons for vaccine hesitancy) were grouped into three dimensions (believes in vaccine effectiveness but concerned about side effects, believes in the importance of taking COVID vaccine, trusts information about COVID vaccine), based on how each item loads on to each of three factors. Cluster 1 was that they believe in effectiveness of vaccine but are concerned about side effects (.92094). Conclusion: Mothers' concerns were mainly about the safety and adverse effects of vaccine.

Regulating Enzyme Catalysis by Tailored Silver Nanocrystals Fabricated with Holigarna arnottiana-Synthesis, Characterization, and Performance Optimization.

Modification of catalytic expression of enzymes and regulating their in vivo activity are the goals of novel treatment strategies. A green synthetic nanostructured silver with potent trypsin inhibitory properties has not yet been developed, despite the fact that silver nanoparticles possess unique properties that allow them to efficiently block enzymes. The present study demonstrates for the first time a facile, safe, economic, and eco-friendly synthetic route for silver nanoparticles using an aqueous extract of Holigarna arnottiana bark engineered to interact with trypsin and hinder its activity effectively. The studies carried out to examine the interaction between these biofabricated AgNPs (HaAgNPs) and trypsin by UV-visible spectrophotometry and FTIR spectroscopy suggest that the formation of trypsin-HaAgNP complex is responsible for diminishing the catalytic efficiency of trypsin. In vivo studies on Aedes aegypti larval serum support these instrumental results of HaAgNP-induced trypsin inhibition and proves its application as a biopesticide. It is noteworthy that the bioengineered HaAgNPs were also found to have good inhibition potential against pepsin and urease as well. A variety of methods have been employed to characterize the synthesized biocompatible HaAgNPs and it possesses a characteristic absorption maximum of 420 nm. Their shelf life of above 7 years is noticeable, since none of the reported green synthesized AgNPs possess a shelf life of more than 1 year. Altogether, this work demonstrates that biofabricated HaAgNPs are multifunctional and cost-resilient biological tools that can be used as enzyme regulators possessing antioxidant, antimicrobial, and insecticidal features.

Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride.

For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by 1H NMR translation self-diffusometry and is further corroborated by 13C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (pb) and equivalent partition coefficient (K) of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates (R1SEL and R1NS, respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.

Magnetic and Magnetostrictive Properties of Sol-Gel-Synthesized Chromium-Substituted Cobalt Ferrite.

Chromium (Cr)-doped cobalt ferrite nanoparticles were synthesized using a sol-gel autocombustion method, with the chemical formula CoCrxFe2xO4. The value of x ranged from 0.00 to 0.5 in 0.1 increments. X-ray diffraction analysis confirmed the development of highly crystalline cubic spinel structures for all samples, with an average crystallite size of approximately 40 to 45 nm determined using the Scherrer equation. Pellets were prepared using a traditional ceramic method. The magnetic and magnetostrictive properties of the samples were tested using strain gauge and VSM (vibrating sample magnetometer) techniques. The results of the magnetic and magnetostrictive tests showed that the chromium-substituted cobalt ferrites exhibited higher strain derivative magnitudes than pure cobalt ferrite. These findings indicated that the introduction of chromium into the cobalt ferrite structure led to changes in the material's magnetic properties. These changes were attributed to anisotropic contributions, resulting from an increased presence of Co2+ ions at B-sites due to the chromium substitutions. In summary, this study concluded that introducing chromium into the cobalt ferrite structure caused alterations in the material's magnetic properties, which were explained by changes in the cationic arrangement within the crystal lattice. This study successfully explained these alterations using magnetization and coercivity data and the probable cationic dispersion.

Sedimentary seagrass carbon stock and sources of organic carbon across contrasting seagrass meadows in Indonesia.

Seagrass meadows are an important component of coastal ecosystems globally, and they capture and store organic carbon in living biomass and sediments. Geographical estimates of blue carbon in seagrass habitats are regionally biased, with limited information from the Indo-Pacific region, including Indonesia. Seagrass extent in Indonesia is declining rapidly, and it has been suggested that marine protected areas (MPAs) are an important instrument to support protection of seagrass ecosystems and their services. Thus, this study is aimed at quantifying and comparing sedimentary carbon stocks and sources of organic carbon from seagrass meadows located in undisturbed areas outside MPA, disturbed areas outside MPA, and within MPA in three small islands in Indonesia. The sediment carbon stocks from this study ranged from 19.81 to 117.49 Mg C ha-1, with the highest stock measured inside MPA (77.15 ± 1.38 Mg C ha-1), followed by undisturbed outside MPA (36.08 Mg C ha-1), and the lowest stock at disturbed outside MPA (21.86 ± 0.31 Mg C ha-1). The predominant source of organic carbon in disturbed meadows was from coastal POM (particulate organic matter, ~ 36%), while in MPA and undisturbed sites, the main source was from seagrass, with ~ 38% and ~ 60% contributions, respectively. The results of this study add more data and information on seagrass blue carbon potential from three different islands with different degrees of disturbance in Indonesia.

Evaluation of Immunohistochemistry Technique for Diagnosis of Extrapulmonary Tuberculosis in Biopsy Tissue Specimen as Compared to Composite Diagnostic Criteria.

Introduction: Diagnosis of extrapulmonary tuberculosis (EPTB) has been challenging owing to its paucibacillary nature and diverse clinical manifestations. Immunohistochemistry (IHC) on biopsy specimens has presented a new perspective toward improving tuberculosis diagnosis. MPT64 is a unique antigen that has shown high sensitivity and specificity compared to other conventional techniques in its ability to diagnose tuberculosis as well as differentiate it from nontubercular mycobacteria. In this study, we aimed to analyze the utility of anti-MPT64 in the diagnosis of EPTB. Methods: In this cross-sectional study, conducted over a period of 1 year, 52 nonrepetitive samples from 52 participants with a presumptive diagnosis of EPTB were collected and processed. The specimens were subjected to Ziehl-Neelsen staining, GeneXpert, tissue culture by mycobacterium growth indicator tube, H and E staining, and IHC with anti-MPT64. The sensitivity and specificity of anti-MPT64 was computed against a composite diagnostic criterion. Results: Fifty-two consecutive participants satisfying the study criteria were recruited. The mean age of the study population was 37.35 ± 18.71 years. Lymph node specimen accounted for majority of the specimen processed (n = 20, 38.5%). The sensitivity of anti-MPT64 in the diagnosis of EPTB was 68.29%, specificity was 90.90%, positive predictive value was 96.55%, and negative predictive value was 43.47%, when composite criteria were considered standard for diagnosis. Conclusion: Immunohistochemical staining by anti-MPT64 is useful in establishing microbiological diagnosis of EPTB on biopsy specimens.

Arginine Depletion in Human Cancers.

Arginine is encoded by six different codons. Base pair changes in any of these codons can have a broad spectrum of effects including substitutions to twelve different amino acids, eighteen synonymous changes, and two stop codons. Four amino acids (histidine, cysteine, glutamine, and tryptophan) account for over 75% of amino acid substitutions of arginine. This suggests that a mutational bias, or "purifying selection", mechanism is at work. This bias appears to be driven by C > T and G > A transitions in four of the six arginine codons, a signature that is universal and independent of cancer tissue of origin or histology. Here, we provide a review of the available literature and reanalyze publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC). Our analysis identifies several genes with an arginine substitution bias. These include known factors such as IDH1, as well as previously unreported genes, including four cancer driver genes (FGFR3, PPP6C, MAX, GNAQ). We propose that base pair substitution bias and amino acid physiology both play a role in purifying selection. This model may explain the documented arginine substitution bias in cancers.

pH-sensitive chitosan nanoparticles loaded with dolutegravir as milk and food admixture for paediatric anti-HIV therapy.

The present study aims to develop Chitosan-based polymeric nanoparticles of anti-HIV drug Dolutegravir, to aid appropriate dose adjustment and ease of oral administration as milk and food admixture for children. The isolated Chitosan from the crab shell species Portunus Sanguinolentus has been characterized for their physicochemical properties. Nanoparticles were developed with varying ratio of drug: Chitosan and assessed for particle size (140-548 nm), zeta potential (+26.1 mV) with a maximum of 75 % drug content. Nanoparticles exhibited improved stability and drug release in the 0.1 N HCl medium compared to pure drug. The MTT assay and the Syncytia inhibition assay in C8166 (T-lymphatic cell line) infected with HIVIIIB viral strain, which showed better therapeutic efficiency and lesser cytotoxicity compared to the pure drug. In consonance with the data obtained, the use of chitosan from a novel source for drug delivery carrier has opened exceptional prospects for delivering drugs efficiently to paediatrics.

Medication errors in neonatal intensive care unit of a tertiary care hospital in South India: A prospective observational study.

INTRODUCTION: Medication errors (MEs) can prolong hospital stay and are a cause of morbidity and mortality. Studies evaluating MEs and its determinants in Indian neonatal intensive care units (NICUs) are limited. Therefore, this study was done to assess the prevalence, characteristics, determinants, and outcomes of MEs in an Indian NICU setting. METHODOLOGY: A prospective observational study was conducted over a 1-year period (January-December 2016) among neonates receiving medications in NICU. Systematic random sampling was done, and data were collected using a semi-structured questionnaire after obtaining informed consent from the mother. An ME self-reporting system was also established. Data were analyzed using Chi-squared test and Student's t-test. Binary logistic regression was used to analyze the determinants of MEs. RESULTS: Among 269 babies included in the study, 57% (n = 154) were male babies with mean (standard deviation [SD]) birth weight of 2.59 kg (0.701). About 79% (n = 213/269) of the neonates were appropriate for gestational age. The mean (SD) duration of stay in NICU was 7.58 (5.07) days, and 67% of the babies had polypharmacy (use of ≥5 medications). The prevalence of MEs was 22% (95% confidence interval [CI]: 16.96%, 26.84%, n = 108) of all babies, of which only 2% (n = 2) were life threatening. Seventy-seven percent (n = 83) of these errors occurred during administration/preparation and 18% (n = 19) while prescribing. The significant determinants of MEs (adjusted odds ratio [95% CI]) include polypharmacy (4.126 [1.917-8.880]), duration of stay >7 days (1.335 [1.198-1.488]), and babies referred from outside (2.592 [1.217-5.521]). CONCLUSIONS: MEs were common in NICU setting. The occurrence of life-threatening MEs was minimal. Longer duration of hospital stay, polypharmacy, and babies born outside were significantly associated with occurrence of MEs.

Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer.

MENIN is a scaffold protein encoded by the MEN1 gene that functions in multiple biological processes, including cell proliferation, migration, gene expression, and DNA damage repair. MEN1 is a tumor suppressor gene, and mutations that disrupts MEN1 function are common to many tumor types. Mutations within MEN1 may also be inherited (germline). Many of these inherited mutations are associated with a number of pathogenic syndromes of the parathyroid and pancreas, and some also predispose patients to hyperplasia. In this study, we cataloged the reported germline mutations from the ClinVar database and compared them with the somatic mutations detected in cancers from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We then used statistical software to determine the probability of mutations being pathogenic or driver. Our data show that many confirmed germline mutations do not appear in tumor samples. Thus, most mutations that disable MEN1 function in tumors are somatic in nature. Furthermore, of the germline mutations that do appear in tumors, only a fraction has the potential to be pathogenic or driver mutations.

Applying Artificial Intelligence to Mitigate Effects of Patient Motion or Other Complicating Factors on Image Quality.

Artificial intelligence, particularly deep learning, offers several possibilities to improve the quality or speed of image acquisition in magnetic resonance imaging (MRI). In this article, we briefly review basic machine learning concepts and discuss commonly used neural network architectures for image-to-image translation. Recent examples in the literature describing application of machine learning techniques to clinical MR image acquisition or postprocessing are discussed. Machine learning can contribute to better image quality by improving spatial resolution, reducing image noise, and removing undesired motion or other artifacts. As patients occasionally are unable to tolerate lengthy acquisition times or gadolinium agents, machine learning can potentially assist MRI workflow and patient comfort by facilitating faster acquisitions or reducing exogenous contrast dosage. Although artificial intelligence approaches often have limitations, such as problems with generalizability or explainability, there is potential for these techniques to improve diagnostic utility, throughput, and patient experience in clinical MRI practice.

Fusarium oxysporum f. sp. lycopersici causal agent of vascular wilt disease of tomato: Biology to diversity- A review.

Tomato (Lycopersicon esculentum) is one of the widely grown vegetables worldwide. Fusarium oxysporum f. sp. lycopersici (FOL) is the significant contributory pathogen of tomato vascular wilt. The initial symptoms of the disease appear in the lower leaves gradually, trail by wilting of the plants. It has been reported that FOL penetrates the tomato plant, colonizing and leaving the vascular tissue dark brown, and this discoloration extends to the apex, leading to the plants wilting, collapsing and dying. Therefore, it has been widely accepted that wilting caused by this fungus is the result of a combination of various physiological activities, including the accumulation of fungal mycelia in and around xylem, mycotoxin production, inactivation of host defense, and the production of tyloses; however, wilting symptoms are variable. Therefore, the selection of molecular markers may be a more effective means of screening tomato races. Several studies on the detection of FOL have been carried out and have suggested the potency of the technique for diagnosing FOL. This review focuses on biology and variability of FOL, understanding and presenting a holistic picture of the vascular wilt disease of tomato in relation to disease model, biology, virulence. We conclude that genomic and proteomic approachesare greater tools for identification of informative candidates involved in pathogenicity, which can be considered as one of the approaches in managing the disease.

Evidence of nanoemulsion as an effective control measure for fruit flies Drosophila melanogaster.

Pesticide resistance is a common concern. It exerts close association with economic and health associated problems in various plants and other organisms. Several approaches have been trialled for attracting and trapping the insects and flies that are acting as vectors for transmission of communicable diseases. Although Drosophila melanogaster (fruit flies) is not an agricultural pest, its presence in consumer dwelling areas is an objection to human, as it indicates signs of an unhealthy environment or products. The current study focuses on the development of nanoemulsion with synthetic attractants and entrapping in sticky glue formulation that could provide prolonged effect for attracting and trapping the fruit flies. The results of our study showed the efficient attractive ability of exposed nanoemulsion (A3E1T) containing amyl acetate, ammonia, ethanol and Tween 80 compared to that of control. While the sex-based effect was not very prominent, the nanoemulsion showed a higher relative response index to the flies and increased activity even during their siesta time. Therefore, the nanoemulsion-based approach could be identified as one of the promising lines of attack and a suitable alternative for the existing fruit fly control measures. The present study is the first of its kind in reporting the ability of nanoemulsion formulation to attract and influence the activity of fruit flies D. melanogaster, up to our best of knowledge.