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Nitrofuran and pyrazolopyrimidine-based compounds possess a broad antimicrobial spectrum including Gram-positive and Gram-negative bacteria. In the present work, a series of conjugates of these scaffolds was synthesized and evaluated for antimicrobial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Many compounds showed MIC values of ≤2 μg ml -1 , with compound 35 demonstrating excellent activity (MICs: 0.7 and 0.15 μg ml -1 against S. aureus and MRSA, respectively) and safety up to 50 μg ml -1 in HepG2 cells. Compound 35 also exhibited no hemolytic activity, biofilm eradication, and effectiveness against efflux-pump-overexpressing strains (NorA, TetK, MsrA) without resistance development. It showed synergistic effects with vancomycin ( S. aureus ) and rifampicin (MRSA). Mechanistic studies revealed that compound 35 exhibits good membrane-targeting abilities, as evidenced by DAPI/PI staining and scanning electron microscopy (SEM). In an intracellular model, it reduced bacterial load efficiently in both S. aureus and MRSA strains. With a strong in vitro profile, compound 35 demonstrated favorable oral pharmacokinetics at 30 mg kg -1 and potent in vivo anti-MRSA activity, highlighting its potential against antibiotic-resistant infections., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

Arecanut palm is a commercially important plantation crop valued for its nut. In this investigation, we report the discovery of a putative novel arepavirus, named areca palm necrotic ringspot virus 2 (ANRSV2), in necrotic ringspot diseased areca palms in Bantwal, Dakshina Kannada, Karnataka, India through RNA-sequencing and transmission electron microscopy. Further, the presence of ANRSV2 in the diseased samples was confirmed through reverse transcriptase-polymerase chain reaction assays. In addition, by mining public domain transcriptome data for arepaviral sequences, we identified a putative novel arepavirus in Psychotria rubra, a non-palm host. We recovered the genome sequences of the areca palm necrotic ringspot virus in honey bees, tomato, Onobrychis viciifolia, and Rhamnus heterophylla. These findings broaden our comprehension of arepaviral diversity and host range, and suggest an intriguing possibility of pollen-mediated arepaviral transmission that necessitates empirical validation. Further studies are needed to understand the biology of identified putative novel arepaviruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

HIV-1 protease (PR) enzyme is a viable antiretroviral drug target due to its crucial role in HIV maturation. Over many decades, the HIV-1 PR enzyme has exhibited mutations brought on by drug pressure and error-prone nature of HIV-1 reverse transcriptase. Non-active site mutations have played a pivotal role in drug resistance; however, their mechanism of action has not been fully elucidated. We investigated how non-active site mutations affect the conformational stability and drug binding ability of HIV-1 PR. In light of this, we studied a novel HIV-1 subtype C protease variant containing an insertion of valine (↑V) in the hinge region. We analysed the mutations in the presence and absence of ten background mutations. Molecular dynamics simulations revealed that both with and without the background mutations, the PR exhibited increased flexibility of hinge, flaps and fulcrum regions. This allowed the PR to adopt a wider flap conformation when in complex with several inhibitors. Additionally, the simulations revealed that the protease inhibitors (PIs) could not bring the mutated variant proteases into a stable, closed conformation, resulting in increased solvent exposure of the inhibitors. Together, these results suggest that the mutations decrease the favourability of binding by altering the dynamics of the flap regions. Notably, the insertion mutation increased PR hinge flexibility and the introduction of background mutations compensated for this by stabilising the cantilever and hinge regions. Together, these findings provide insight into how non-active site mutations affect PR conformational dynamics in critical areas of the PR thus impacting on drug binding capacity and potentially contributing to drug resistance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasien Sayed reports financial support was provided by University of the WitwatersrandJohannesburg School of Molecular and Cell Biology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The insecticide susceptibility of Helopeltis theivora Waterhouse (Hemiptera: Miridae) is being evaluated using shoot and glass-vial assay as described by IRAC. However, the reliability of the assay depends on feeding preference and contact toxicity. Hence, the cocoa pod was used as a substrate to test the susceptibility of H. theivora in comparison with existing methods. The experimental results revealed that the LC 50 value of all of the insecticides was relatively lower in the pod bioassay than the other two methods and exhibited maximum mortality within 6 hr of post-exposure. Among insecticides, fipronil was the most effective molecule followed by lambda-cyhalothrin. H. theivora , which prefers to feed on a pod due to more tissue turgidity, thus facilitated adequate sap ingestion; whereas, these were limited in shoot and glass-vial bioassays. Therefore, it could be used as a methodology to determine the susceptibility of H. theivora against a wide range of insecticide molecules., Competing Interests: Conflict of interestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Pesticide Science Society of Japan.)

The two transesterification reactions of pre-mRNA splicing require highly complex yet well-controlled rearrangements of small nuclear RNAs and proteins (snRNP) in the spliceosome. The efficiency and accuracy of these reactions are critical for gene expression, as almost all human genes pass through pre-mRNA splicing. Key parameters that determine the splicing outcome are the length of the intron, the strengths of its splicing signals and gaps between them, and the presence of splicing controlling elements. In particular, the gap between the branchpoint (BP) and the 3' splice site (ss) of introns is a major determinant of the splicing efficiency. This distance falls within a small range across the introns of an organism. The constraints exist possibly because BP and 3'ss are recognized by BP-binding proteins, U2 snRNP and U2 accessory factors (U2AF) in a coordinated manner. Furthermore, varying distances between the two signals may also affect the second transesterification reaction since the intervening RNA needs to be accurately positioned within the complex RNP machinery. Splicing such pre-mRNAs requires cis-acting elements in the RNA and many trans-acting splicing regulators. Regulated pre-mRNA splicing with BP-distant 3'ss adds another layer of control to gene expression and promotes alternative splicing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction Asthma is one of the serious health problems among children, accounting for a major proportion of lost school days due to absenteeism, decreased academic performances, and lesser social interactions. It can impair a child's activities like playing sports and also their sleeping pattern with frequent school absenteeism. In South India, only a few school-based studies to determine the prevalence of asthma have been carried out, and even fewer studies are done in community settings in rural areas of Tamil Nadu. Hence, this community-based study was done to find out the prevalence of asthma among children aged 5-10 years in rural areas of Coimbatore, Tamil Nadu. Aim & objective To estimate the prevalence of asthma among children aged 5-10 years in rural areas of Coimbatore, Tamil Nadu. Materials and methods A community-based cross-sectional study was conducted in rural areas of Coimbatore, Tamil Nadu. A sample of 726 children from the randomly selected seven villages were studied. The sample size was calculated for a finite population. The standardized International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and calibrated instruments were used as data collection tools. Ethical approval was obtained. Data entry was done in Microsoft Excel and analyzed using the SPSS 19.0 version. The "t" test was used to compare the mean difference between the quantitative variables and the chi-square test was used to test the association between categorical variables. P-value <0.05 was considered as statistically significant. Results The overall prevalence of self-reported asthma was 5.1%. Boys had 1.7 times higher prevalence compared to girls. The prevalence of possible or suspected cases of asthma using the ISAAC screening questionnaire was 20.9%. In univariate analysis, the risk of having asthma among children is significantly higher among those with a positive family history of asthma. Conclusion The study found that the prevalence of self-reported asthma in rural settings is low (5.1%). However, our study also identifies a large number of children (20.9%) with symptoms suggestive of asthma using the ISAAC questionnaire that need the attention of a specialist for early diagnosis and care for reducing morbidity and episode severity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Human Ethics Committee, PSG Institute of Medical Sciences & Research issued approval 13/390. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Balakrishnan et al.)

Betaine-30 (B30) was reported by Karl Dimroth and Christian Reichardt et al. in 1963 as a solvatochromic probe that can be easily synthesized, shows good solubility, and remains stable in various organic solvents and solutions. Its strongly negatively solvatochromic behavior arises from differential solvation between its electronic ground and excited states, making it a valuable tool for assessing solvent polarity using the E T (30) polarity scale, also devised by Dimroth and Reichardt. In addition, advancements in femtosecond laser spectroscopy in the 1990s greatly improved the understanding of B30's relaxation dynamics following photoexcitation. In solvents capable of hydrogen bonding, such as alcohols, intermolecular hydrogen-bond rearrangement contributes to the multiple relaxation components observed. Since the 1990s, the applications of B30 have expanded beyond simple organic solvents to include complex solvent mixtures, such as electrolyte solutions for battery technologies and eutectic solvent mixtures. Given the growing importance of these complex solvent mixtures, B30 is becoming an increasingly valuable tool for studying previously unexplored solvation properties.

Recent advances in automated scoring technology have made it practical to replace multiple-choice questions (MCQs) with short-answer questions (SAQs) in large-scale, high-stakes assessments. However, most previous research comparing these formats has used small examinee samples testing under low-stakes conditions. Additionally, previous studies have not reported on the time required to respond to the two item types. This study compares the difficulty, discrimination, and time requirements for the two formats when examinees responded as part of a large-scale, high-stakes assessment. Seventy-one MCQs were converted to SAQs. These matched items were randomly assigned to examinees completing a high-stakes assessment of internal medicine. No examinee saw the same item in both formats. Items administered in the SAQ format were generally more difficult than items in the MCQ format. The discrimination index for SAQs was modestly higher than that for MCQs and response times were substantially higher for SAQs. These results support the interchangeability of MCQs and SAQs. When it is important that the examinee generate the response rather than selecting it, SAQs may be preferred. The results relating to difficulty and discrimination reported in this paper are consistent with those of previous studies. The results on the relative time requirements for the two formats suggest that with a fixed testing time fewer SAQs can be administered, this limitation more than makes up for the higher discrimination that has been reported for SAQs. We additionally examine the extent to which increased difficulty may directly impact the discrimination of SAQs., (© 2023. NBME.)

We demonstrate template-assisted growth of gallium-based nanoparticle clusters on silicon substrate using a focused ion beam (FIB) nanolithography technique. The nanolithography counterpart of the technique steers a focussed 30 kV accelerated gallium ion beam on the surface of Si to create template patterns of two-dimensional dot arrays. Growth of the nanoparticles is governed by two vital steps namely implantation of gallium into the substrate via gallium beam exposure and formation of the stable nanoparticles on the surface of the substrate by subsequent annealing at elevated temperature in ammonia atmosphere. The growth primarily depends on the dose of implanted gallium which is in the order of 10 7 atoms per spot and it is also critically influenced by the temperature and duration of the post-annealing treatment. By controlling the growth parameters, it is possible to obtain one particle per spot and particle densities as high as 10 9 particles per square centimetre could be achieved in this case. The demonstrated growth process, utilizing the advantages of FIB nanolithography, is categorized under the guided organization approach as it combines both the classical top-down and bottom-up approaches. Patterned growth of the particles could be utilized as templates or nucleation sites for the growth of an organized array of nanostructures or quantum dot structures., (© 2024 IOP Publishing Ltd.)

Background: Depression among people living with human immunodeficiency virus (PLHIV) is highly prevalent and it is associated with increased morbidity, poor adherence to antiretroviral therapy, and poor psychosocial outcomes. To address this, integrated counselling and testing centres (ICTC) counsellors provide psychosocial support to PLHIV., Materials and Methods: This descriptive study aims to assess the awareness and knowledge of ICTC counsellors about depression and its management. A total of 338 ( n = 452) ICTC counsellors participated in the study. A demographic data sheet and a semi-structured questionnaire were used to collect data., Results: More than half of the participants reported that biochemical imbalances cause depression. 71.60% and 79.59% of participants reported that depression was common among PLHIV and required immediate attention. 92.60% of counsellors reported that a combination of counselling and medication would be effective to treat depression. 86.98% and 81.95% of counsellors were confident and actively screened for depression among PLHIV, and 78.11% of counsellors had access to a psychiatrist. In contrast. One-third of participants had difficulties working with PLHIV, and 55.56% of participants expressed that addressing issues of PLHIVs' depression to be left to mental health professionals., Conclusion: ICTC counsellors had adequate knowledge about depression and its symptoms. However, lack of knowledge on intervention strategies, time constraints and work targets are significant barriers. These findings suggest that training on mental illness screening; brief intervention strategies may help counsellors to assist PLHIV in overcoming depression complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Industrial Psychiatry Journal.)

Deep eutectic solvents (DESs) are a class of versatile solvents with promise for a wide range of applications, from separation processes to electrochemical energy storage technologies. A fundamental understanding of the correlation among the structure, thermodynamics, and dynamics of these materials necessary for targeted rational design for specific applications is still nascent. Here, we employ differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS), and femtosecond transient absorption spectroscopy (fs-TAS) to investigate the correlation among thermodynamics, dynamics, and charge transport in mixtures comprising a wide range of compositions of choline chloride (ChCl) and ethylene glycol (EG). Detailed analyses reveal that (i) the eutectic composition of this prototypical DES occurs in the 15-20 mol % ChCl in the EG range rather than the previously assumed 33 mol %, and (ii) both rotational dynamics and charge transport at the eutectic composition are enhanced in this composition range. These findings highlight the fundamental interplay between thermodynamics and dynamics in determining the properties of DESs that are relevant to many applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of NAD + , which is crucial to the survival of bacterial pathogens. However, no information is available on the structure-function of Enterococcus faecium NNAT (EfNNAT). This study established the expression and purification protocol for obtaining a high-yield recombinant EfNNAT using the E. coli expression system and a single-step IMAC purification method. Approximately 101 mg of EfNNAT was obtained per 7.8 g of wet E. coli cells, estimated to be over 98 % pure. We further characterized the biophysical structure and determined the three-dimensional structure of the EfNNAT. Biophysical studies revealed a dimeric protein with a higher α-helical composition. The highly stable protein crystalizes in multiple conditions, yielding high-quality crystals diffracting between 1.78 and 2.80 Å. Two high-resolution crystal structures of EfNNAT in its native and adenine-bound forms were determined at 1.90 Å and 1.82 Å, respectively. The X-ray structures of the EfNNAT revealed the presence of phosphate and sulfate ions occupying and interacting with conserved amino acid residues within the putative substrate binding site, hence providing insight into the probable substrate preference of EfNNAT and, consequently, why EfNNAT may not prefer β-nicotinamide mononucleotide as a substrate. With the accessibility to high-resolution structures of EfNNAT, further structural evaluation and drug-based screening can be achieved. Hence, we anticipate that this study will provide the basis for the discovery of structure-based inhibitors against this enzyme., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ikechukwu Achilonu reports financial support was provided by National Research Foundation of South Africa. Ikechukwu Achilonu reports financial support was provided by South African Medical Research Council., (Copyright © 2023. Published by Elsevier B.V.)

Fungicidal application has been the common and prime option to combat fruit rot disease (FRD) of arecanut ( Areca catechu L.) under field conditions. However, the existence of virulent pathotypes, rapid spreading ability, and improper time of fungicide application has become a serious challenge. In the present investigation, we assessed the efficacy of oomycete-specific fungicides under two approaches: (i) three fixed timings of fungicidal applications, i.e., pre-, mid-, and post-monsoon periods (EXPT1), and (ii) predefined different fruit stages, i.e., button, marble, and premature stages (EXPT2). Fungicidal efficacy in managing FRD was determined from evaluations of FRD severity, FRD incidence, and cumulative fallen nut rate (CFNR) by employing generalized linear mixed models (GLMMs). In EXPT1, all the tested fungicides reduced FRD disease levels by >65% when applied at pre- or mid-monsoon compared with untreated control, with statistical differences among fungicides and timings of application relative to infection. In EXPT2, the efficacy of fungicides was comparatively reduced when applied at predefined fruit/nut stages, with statistically non-significant differences among tested fungicides and fruit stages. A comprehensive analysis of both experiments recommends that the fungicidal application can be performed before the onset of monsoon for effective management of arecanut FRD. In conclusion, the timing of fungicidal application based on the monsoon period provides better control of FRD of arecanut than an application based on the developmental stages of fruit under field conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Balanagouda, Shil, Sridhara, Pandian, Thube, Hegde, Sayed, Casini and Narayanaswamy.)

A tractor mounted air blast sprayer was designed and developed to reduce the drudgery involved in the manual spraying of pesticide by climbing coconut tree. The sprayer mounted on a small tractor, prime mover, is operated by the power taken from its power take off (PTO). In this study, the influence of two important parameters viz., blower speed (2250 and 3000 rpm) and tractor speed (1.5 and 2.5 km h -1 ) at different heights on the spray characteristics such as volume mean diameter (VMD), droplet density, and spray deposition were collected and analysed. The tractor speed of 1.5 kmh -1 and blower speed of 3000 rpm was observed at recommended VMD between 100-200 µm at a height above 21 m. Hence, the tractor speed of 1.5 kmh -1 and blower speed of 3000 rpm was selected for field evaluation. The mean height of the coconut tree in the tested field was 24 m. The mean droplet size and deposition were observed at 124 µm and 7.2 µl cm -2 , respectively at 24 m height. The effective field capacity, field efficiency, and fuel consumption were 0.524 ha.h -1 , 73.72%, and 4.67 l h -1 , respectively.

The use of adjuvant therapy is an attractive approach to manage sickle cell disease (SCD) symptomatically. The present study aimed to investigate the potential of ellagic acid as an adjuvant therapy with hydroxyurea (HU), a key drug for SCD with myelosuppressive toxic effects. A panel of experiments was performed using SCD patient's blood (ex vivo) and transgenic mice model of SCD (in vivo). Ellagic acid exhibited the following beneficial pharmacological actions: (a) potent anti-sickling, polymerization inhibitory, and inherent non-hemolytic activity; (b) pronounced action to abrogate HU-induced neutropenia and to improve key hematological parameters during SCD (RBC, Hb, platelet levels); (c) considerable action to foster vascular tone (L-proline); (d) marked attenuating effect against oxidative stress (nitrotyrosine, hypoxanthine, MDA, GSH); (e) substantial inhibitory role against inflammation (analgesic activity and regulation of hemin, TNF-α, IL-1β, NF-κB/IκBα); (f) remarkable outcome of declining vaso-occlusive crisis (P-selectin, ERK1/2); (g) notable shielding deed against elevated biochemical marker for organ toxicity (creatinine); (h) noticeably prevented histopathological alterations of the spleen. Additionally, the pharmacokinetic study results of HU in the presence and absence of ellagic acid using a mouse model demonstrate that ellagic acid could be safely co-administered with HU. Overall findings suggest that ellagic acid is a promising candidate for adjuvant therapy in SCD based on its own significant ability against SCD and potentiating capability of HU action via targeting improvement at the various stages of pathophysiological complications during SCD and minimizing HU-induced toxicological manifestations., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Acquired immunodeficiency syndrome (AIDS) is one of the most challenging infectious diseases to treat on a global scale. Understanding the mechanisms underlying the development of drug resistance is necessary for novel therapeutics. HIV subtype C is known to harbor mutations at critical positions of HIV aspartic protease compared to HIV subtype B, which affects the binding affinity. Recently, a novel double-insertion mutation at codon 38 (L38HL) was characterized in HIV subtype C protease, whose effects on the interaction with protease inhibitors are hitherto unknown. In this study, the potential of L38HL double-insertion in HIV subtype C protease to induce a drug resistance phenotype towards the protease inhibitor, Saquinavir (SQV), was probed using various computational techniques, such as molecular dynamics simulations, binding free energy calculations, local conformational changes and principal component analysis. The results indicate that the L38HL mutation exhibits an increase in flexibility at the hinge and flap regions with a decrease in the binding affinity of SQV in comparison with wild-type HIV protease C. Further, we observed a wide opening at the binding site in the L38HL variant due to an alteration in flap dynamics, leading to a decrease in interactions with the binding site of the mutant protease. It is supported by an altered direction of motion of flap residues in the L38HL variant compared with the wild-type. These results provide deep insights into understanding the potential drug resistance phenotype in infected individuals., Competing Interests: The authors declare no conflicts of interest.

The ultra-thin heterostructure of Pr 0.6 Sr 0.4 MnO 3 (15 nm)/Pr 0.5 Ca 0.5 MnO 3 (15 nm)/SrTiO 3 fabricated using pulsed laser deposition technique exhibits the phase-segregated nature wherein the ferromagnetism of Pr 0.6 Sr 0.4 MnO 3 , and the antiferromagnetic state of Pr 0.5 Ca 0.5 MnO 3 coexist in proximity. The observation of two exciting phenomena in the grown ultra-thin heterostructure, namely, the kinetic arrest and training effect, confirms its phase-segregated nature. The melting of the antiferromagnetic state in Pr 0.5 Ca 0.5 MnO 3 into a ferromagnetic state due to the interfacial interaction arising from the magnetic proximity of the ferromagnetic clusters of Pr 0.6 Sr 0.4 MnO 3 have been observed. A metal-insulator transition (T MIT ) found at 215 K, close to its Curie temperature (T Curie ) observed at 230 K, reveals a strong correlation between the electrical transport and the magnetization of the ultra-thin heterostructure. The electrical conduction in the high-temperature regime is explained in terms of the adiabatic small polaron hopping model. While the resistance in the metallic regime for temperatures above 100 K is contributed by the inelastic scattering due to the two-magnons, in the metallic regime below 100 K, the one-magnon inelastic scattering contribution is prevalent. An enhanced colossal magnetoresistance property near room temperature is obtained in the ultra-thin heterostructure arising from the proximity-driven interfacial interaction, making it a suitable candidate for technological applications near room temperature., (© 2023. The Author(s).)

In this paper, we reported the controlled synthesis of tungsten disulfide/reduced tungsten oxide (WS 2 /W 18 O 49 ) heterojunctions for highly efficient room temperature NO x and ammonia (NH 3 ) sensors. X-ray diffraction analysis revealed the formation of the oxygen-deficient W 18 O 49 phase along with WS 2 . Field-emission scanning electron microscopy and transmission electron microscopy displayed the formation of WS 2 flakes over W 18 O 49 nanorods. X-ray photoelectron spectroscopy showed the presence of tungsten in W 4+ , W 5+ , and W 6+ oxidation states corresponding to WS 2 and W 18 O 49 , respectively. The WS 2 /W 18 O 49 heterojunction sensor exhibited sub-ppm level sensitivity to NO x and NH 3 at room temperature. The heterojunction sensor detected 0.6 ppm NO x and 0.5 ppm NH 3 , with a corresponding response of 7.1 and 3.8%, respectively. The limit of detection of the sensor was calculated to be 0.05 and 0.17 ppm for NH 3 and NO x , respectively. The cyclic stability test showed that the sensor exhibited high stability even after 24 cycles for the detection of NH 3 and 14 cycles for NO x . Compared to pristine WO 3 and WS 2 , the WS 2 /W 18 O 49 heterojunction showed high selectivity toward NO x and NH 3 . The results could be useful for the development of room temperature NO x and NH 3 sensors.

Leishmaniasis, a tropically neglected disease, is responsible for the high mortality and morbidity ratio in poverty-stricken areas. Currently, no vaccine is available for the complete cure of the disease. Current chemotherapeutic regimens face the limitations of drug resistance and toxicity concerns indicating a great need to develop better chemotherapeutic leads that are orally administrable, potent, non-toxic, and cost-effective. The anti-leishmanial drug discovery process accelerated the desire for large-scale drug screening assays and high-throughput screening (HTS) technology to identify new chemo-types that can be used as potential drug molecules to control infection. Using the HTS approach, about one million compounds can be screened daily within the shortest possible time for biological activity using automation tools, miniaturized assay formats, and large-scale data analysis. Classical and modern in vitro screening assays have led to the progression of active compounds further to ex vivo and in vivo studies. In the present review, we emphasized on the HTS approaches employed in the leishmanial drug discovery program. Recent in vitro screening assays are widely explored to discover new chemical scaffolds. Developing appropriate experimental animal models and their related techniques is necessary to understand the pathophysiological processes and disease host responses, paving the way for unraveling novel therapies against leishmaniasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The global HIV/AIDS epidemic still currently affects approximately 38 million individuals globally. The protease enzyme of the human immunodeficiency virus is a major drug target in antiviral therapy, however, under the influence of reverse transcriptase and in the context of drug pressure, the rapid PR mutation rate contributes significantly to clinical failure. The set of cooperative non-active site mutations, I13V/I62V/V77I, have been associated with reduced inhibitor susceptibility and are the focus of the current study. When compared to the wild-type protease the mutant protease exhibited decreased binding affinities towards ATV and DRV by 64- and 12-fold, respectively, and decreased the overall favourable Gibbs free energy for ATV, DRV, RTV and SQV. Moreover, these mutations decreased the thermal stability of the protease when in complex with ATV and DRV by approximately 6.4 and 4.2 °C, respectively. The crystal structure of the mutant protease revealed that the location of these mutations and their effect on the hydrophobic sliding mechanism may be crucial in their role in resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intron diversity facilitates regulated gene expression and alternative splicing. Spliceosomes excise introns after recognizing their splicing signals: the 5'-splice site (5'ss), branchpoint (BP) and 3'-splice site (3'ss). The latter two signals are recognized by U2 small nuclear ribonucleoprotein (snRNP) and its accessory factors (U2AFs), but longer spacings between them result in weaker splicing. Here, we show that excision of introns with a BP-distant 3'ss (e.g. rap1 intron 2) requires the ubiquitin-fold-activated splicing regulator Sde2 in Schizosaccharomyces pombe. By monitoring splicing-specific ura4 reporters in a collection of S. pombe mutants, Cay1 and Tls1 were identified as additional regulators of this process. The role of Sde2, Cay1 and Tls1 was further confirmed by increasing BP-3'ss spacings in a canonical tho5 intron. We also examined BP-distant exons spliced independently of these factors and observed that RNA secondary structures possibly bridged the gap between the two signals. These proteins may guide the 3'ss towards the spliceosome's catalytic centre by folding the RNA between the BP and 3'ss. Orthologues of Sde2, Cay1 and Tls1, although missing in the intron-poor Saccharomyces cerevisiae, are present in intron-rich eukaryotes, including humans. This type of intron-specific pre-mRNA splicing appears to have evolved for regulated gene expression and alternative splicing of key heterochromatin factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Exudation of mucilage from pinhead-sized boreholes in cocoa pods was recorded in Karnataka, India, during 2021. Further investigations showed the association of scolytine beetles with infested pods. The identity of the pest, Xylosandrus crassiusculus , was confirmed through morphological characterization and sequencing of the mitochondrial COI gene. We studied the predisposing factors for its infestation, visible and concealed damaging symptoms, and fungal symbionts. In addition to its well-known symbiotic fungus, Ambrosiella roeperi , a new association of yeast, Ambrosiozyma monospora, was discovered. We also traced the possible role of the mirid bug, Helopeltis theivora, in host selection by X. crassiusculus . Overall results indicated that a 'mirid bug-ambrosia beetle-pathogen complex' is responsible for the severe damage to cocoa pods in South India., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

An oomycetous fungus Phytophthora causing fruit rot is the most devastating disease of arecanut in different agro-climatic zones of Karnataka with varied climatic profiles. The main aim of this investigation was to characterize the geo-distant Phytophthora populations infecting arecanut using robust morphological, multi-gene phylogeny and haplotype analysis. A total of 48 geo-distant fruit rot infected samples were collected during the South-West monsoon of 2017-19. Pure culture of the suspected pathogen was isolated from the infected nuts and pathogenic ability was confirmed and characterized. Colony morphology revealed typical whitish mycelium with stellate or petalloid pattern and appearance with torulose hyphae. Sporangia were caducous, semipapillate or papillate, globose, ellipsoid or ovoid-obpyriform in shape and sporangiophores were irregularly branched or simple sympodial in nature. Subsequent multi-gene phylogeny (ITS, β-tub, TEF-1α and Cox-II) and sequence analysis confirmed the identity of oomycete as Phytophthora meadii which is predominant across the regions studied. We identified 49 haplotypes representing the higher haplotype diversity with varying relative haplotype frequency. Comprehensive study confirmed the existence of substantial variability among geo-distant populations (n = 48) of P. meadii . The knowledge on population dynamics of the pathogen causing fruit rot of arecanut generated from this investigation would aid in developing appropriate disease management strategies to curtail its further occurrence and spread in arecanut ecosystem., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: Health of individuals and community. Occupation, being a significant determinant of health, plays a vital role in the outcome of health. Mining being an occupation has it's own characteristics and occupational hazards. One such factor, being tobacco consumption has been sparsely reported among thermal power station workers., Aims and Objectives: To assess the prevalence of tobacco consumption among thermal power station workers in south India., Materials and Methods: Simple random sampling was used to collect data from the study in the subjects working in thermal power station. Pretested questionnaire was used to collect demographic and prevalence data pertaining to tobacco consumption. Descriptive statistical analysis was done for the data to express the same in frequencies., Results: Among the 401 study subjects, 121 of them consumed tobacco. Among them 59%(n=72) of them used smoking form of tobacco and about 23%(n=28) of them used smokeless form of tobacco. Vast majority73%(n=52) of the smokers used cigarette and 14%(n=19) used bidi., Conclusion: A significant number of workers in thermal power station were found to use tobacco. Further studies are required to be conducted on a larger scale followed by analytical studies to establish the strength of association between the occupation related variables and tobacco consumption., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Objectives: To evaluate the long-term oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) and the impact of diagnostic ureteroscopy (URS) on survival outcomes., Materials and Methods: A retrospective analysis of all consecutive patients undergoing RNU for suspected UTUC at a UK tertiary referral centre from a prospectively maintained database was conducted. The primary outcome measures were 5- and 10-year cancer-specific survival (CSS). The secondary outcomes were: overall survival (OS), recurrence-free survival (RFS), impact of prior diagnostic URS on OS, CSS and intravesical RFS (intravesical-RFS), and predictors of intravesical recurrence. Statistical analysis was performed in R using the 'survminer' and 'survival' packages. The Kaplan-Meier method was used to calculate survival functions and these were expressed in graphical form. Uni-/multivariate survival analyses were performed using the Cox proportional hazard regression model. Statistical significance in this study was set at P < 0.05., Results: A total of 422 patients underwent RNU with confirmed UTUC. The median (interquartile range) follow-up of patients with confirmed UTUC was 9.2 (5.6-12.7) years. The 5- and 10-year CSS rates were 70.5% (95% confidence interval [CI] 65.9-74.9) and 67.1% (95% CI 62.4-71.6), respectively. OS (HR 1.04 [95% CI 0.78-1.38]; P = 0.46) and CSS (HR 0.96 [95% CI 0.68-1.34]; P = 0.81) were similar in the diagnostic URS and the direct RNU cohorts. intravesical RFS was superior for the direct RNU cohort (HR 1.94 [95% CI 1.19-3.17]; P = 0.008). In multivariate analysis, prior URS, T2 stage, proximal ureter tumour and bladder cancer history were predictors of metachronous bladder recurrence., Conclusion: This single-centre retrospective cohort study reports the long-term oncological outcomes of RNU with a median follow-up of 9.2 years, serving as a reference standard in counselling patients undergoing RNU. Stage and grade of the RNU specimen were the only two studied factors that appeared to adversely impact long-term CSS and OS. Our results suggest that the risk of intravesical recurrence is increased nearly twofold in patients who have undergone diagnostic URS prior to RNU. Prior URS, however, does not appear to adversely impact long-term CSS and OS. The authors suggest that a risk-stratified approach be adopted, wherein diagnostic URS is offered only in equivocal cases., (© 2021 The Authors BJU International © 2021 BJU International.)

Background: Obsessive-compulsive disorder (OCD) is known to cause significant burden to patients and their caregivers. However, there is limited data on its impact on family functioning, especially from families with an adult member having OCD., Methods: Four hundred subjects, which included treatment-seeking adult OCD patients (n = 200) and their caregivers (n = 200) were recruited. Patients were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Caregivers were evaluated using the MINI, the Caregiver Strain Index (CSI), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Socio-Occupational Functioning Assessment Scale (SOFAS), the Family Accommodation Scale (FAS) and the Connor-David Resilience scale (CD-RISC) in a cross-sectional interview. Family functioning was measured using the OCD Family Functioning (OFF) Scale. Structural equation modeling (SEM) was carried out to evaluate the relationships between the patient and caregiver variables to predict family functioning., Results: From the best-fitting path model, we ascertained that OCD symptoms did not have a direct relationship with family dysfunction. Their effects were in turn was mediated by family accommodation, anxiety, caregiver stress/burden and depression. "Contamination & washing" was the only significant symptom dimension within the model. Caregiver resilience was found to predict only their individual functioning, and not family functioning., Limitations: Study sample included patients from a tertiary care OCD service, only one caregiver from each patient's family was interviewed., Conclusions: Evaluating family functioning, addressing it as part of interventional modules for patients and caregivers may help improving treatment outcomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Arecanut ( Areca catechu L.) is an important plantation crop cultivated predominantly in the Indian states of Karnataka, Kerala, Assam, West Bengal, and Maharashtra in an area of 5.19 lakh ha, with Karnataka State alone accounting for about 68.41% of the area and 79.97% of production. Arecanut production has recently been hampered due to environmental and disease pressures, especially the escalating incidence of Yellow Leaf Disease (YLD). The involvement of phytoplasma as the etiological agent of YLD has been reported. Symptoms include yellowing at the tip of leaflets of two or three fronds of the outer most whorl which gradually spreads to the inner whorl of leaves. As the disease progresses, the entire crown becomes yellow leaving only the spear leaf green. In severe cases, the affected leaves often show necrosis from their tips. In advanced stages, the leaves are reduced in size and become stiff and pointed and the crown ultimately falls off. Degeneration of cortex is commonly observed in the diseased roots. The kernel of affected nuts shows discolouration and later turns blackish. The reduction in yield over a period of three years, immediately after the incidence of the disease, has been estimated to be around 50%. Harnessing the arecanut-microbiome interactions to address the biotic and abiotic stresses of the host plant offers immense opportunity to increase arecanut production sustainably. Here, we report a comprehensive analysis of the structural composition of the arecanut rhizosphere bacterial diversity utilizing next-generation sequencing (NGS) technology. We have used amplicon sequencing (V3-V4 regions of the 16S rRNA gene) of bulk soil and rhizosphere samples collected from YLD endemic regions of Aranthodu, Sullia Taluk, Dakshina Kannada District, Karnataka State, India, to assess the microbial diversity. The results revealed that while there is a great diversity of bacterial communities, relatively few bacterial phyla predominate with higher relative abundance. The phyla viz ., Proteobacteria, Bacteroidetes, Firmicutes, Acidobacteria, Planctomycetes, Patescibacteria, Chloroflexi, Actinobacteria, Fusobacteria, and Verrucomicrobia were found to be dominant in the rhizosphere of the arecanut., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Inc.)

The past two decades witnessed the development of a new type of solvent system, named deep eutectic solvents, which have become increasingly investigated because they offer new and potentially favorable properties, such as wide tunability in electrochemical, mechanical, and transport properties. Deep eutectic solvent (DES) systems are composed of at least one main solvent and an additional component that is meant to interrupt the original solvent/solvent interactions, thereby introducing lower melting points relative to each individual component. Ethaline (a 1:2 mol % mixture of choline chloride and ethylene glycol) is one of the most promising DES systems. However, it is also known to be very hygroscopic, which is a constant concern because water absorption during the use of ethaline alters its properties. Within this work, we demonstrate that modest amounts of water addition (1-10%) to ethaline are of little concern for practical use and can even lead to performance improvements, such as accelerated relaxation and solvation. In contrast, very small amounts of <1% of water lead to additional slowing of the solvent response. Thus, we suggest that the attempt to dry ethaline below 1% moisture is rather counterproductive if one attempts to achieve effective solvation and charge transport properties from DESs. This study investigates the effect of water content on the diffusional relaxation dynamics of ethaline. A set of independent spectroscopic experiments and computational simulations are aimed to provide insight into the solvent response of the DES system using femtosecond time-resolved absorption spectroscopy (fs-TA), broadband dielectric spectroscopy (BDS), nuclear magnetic resonance (NMR) diffusometry and broadband relaxometry, and molecular dynamics simulations (MDS) on ethaline with 0, 0.1, 1, 10, and 28.5 wt % added water. For dry ethaline, we identify choline chloride as the rate-limiting solvation component in ethaline. However, the role of the solvent components changes gradually as water is added. We provide quantitative solvent relaxation rates using the different presented time-resolved spectroscopic techniques and find remarkable agreement between them. Based on the solvent relaxation rates and combined with MDS, we develop a molecular understanding of the individual solvent components and their interactions in dry and wet ethaline with varying amounts of water content.

Studies show an increase in circulating levels of 25-hydroxyvitamin D [25(OH)D] in women using combined oral contraceptives (COCs). 25(OH)D is a quantitatively important metabolite and widely used clinical marker of vitamin D status and is regulated by vitamin D binding protein (VDBP). However, studies have not identified the type of formulations used by the women, and there are no data on the effect of progestins on 25(OH)D levels. Our study objective was to compare the effects of two COC formulations [ethinyl estradiol (EE)/norethindrone acetate (NETA) vs. EE/levonorgestrel (LNG)] as well as LNG alone on total and bioavailable (free plus albumin-bound) 25(OH)D levels in serum samples collected at baseline, mid treatment, and end of treatment. Total 25(OH)D and VDBP were measured by immunoassay, and bioavailable 25(OH)D was calculated. The results show that with the EE/NETA formulation, total and bioavailable 25(OH)D and VDBP levels increased non-significantly by 7.4 %, 14.9 %, and 10 %, respectively, from baseline to end of treatment. In contrast, the corresponding changes with EE/LNG showed an increase of 4.4 % in total 25(OH)D but a significant decrease of 18.2 % in bioavailable 25(OH)D and increase of 19.1 % in VDBP. When LNG was administered alone, no significant changes were observed in total and bioavailable 25(OH)D or VDBP levels during the course of treatment. Our findings show considerably different effects on total and bioavailable 25(OH)D levels, as well as VDBP levels, with different oral contraceptive formulations. LNG may have a suppressive effect on VDBP, similar to its well-known androgenic effect on SHBG. Further studies are needed to determine the effect of hormonal contraceptive formulations on vitamin D status and its potential impact on women's health., (Copyright © 2021. Published by Elsevier Ltd.)

Thin films of Bi-based superconductors, highly c-axis oriented, were deposited on single crystalline substrates of SrTiO3, LaAlO3, and MgO using a pulsed laser deposition technique with a Bi-2223 target of nominal composition Bi1.75Pb0.25Sr2Ca2Cu3O10±δ prepared by the solid state reaction method. The effect of different deposition parameters on the evolution of the requisite properties in the thin films has been studied. These films have been characterized by X-ray diffraction to investigate their structural properties, scanning electron microscopy to understand the effect of ex situ annealing on the grain growth, and DC resistivity measurements to quantify their superconducting critical temperature. Furthermore, the chemical states of the constituent elements Bi, Pb, Sr, Ca, Cu and O were confirmed using X-ray photoelectron spectroscopy. This information has helped in deciphering the empirical stoichiometry of the films on each of the chosen substrates. We have also been able to comment on the influence made by the choice of the substrates on the mechanism of evolution of superconductivity based on the interplay of the cation chemistry between the substituent and the constituent elements. Thin films with superior superconducting properties were obtained on SrTiO3 substrates with 58% of Bi-2223 phase fraction yielding a superconducting transition temperature (TC,offset) of 107 K. Magnetotransport studies were performed on these films to quantify their superconducting upper critical field and to comprehend the pinning mechanism.

Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as g roup-specific c omponent or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene deletion in a patient with apparent severe vitamin D deficiency, fragility fractures, and ankylosing spondylitis. Here, we report an unrelated patient free of fractures or rheumatologic disease, but with very low 25-hydroxyvitamin D and 1,25-hydroxyvitamin D, as well as undetectable DBP measured by liquid chromatography-tandem mass spectrometry. A whole gene deletion was excluded by microarray, and Sanger sequencing of GC revealed a homozygous pathogenic variant affecting a canonical splice site (c0.702-1G > A). These findings indicate that loss of function variants in GC that eliminate DBP, and severely reduced total circulating vitamin D levels, do not necessarily result in significant metabolic bone disease. Together with our previous report, these cases support the free-hormone hypothesis, and suggest free vitamin D metabolites may serve as preferable indicators of bone and mineral metabolism, particularly when clinical suspicion of DBP deficiency is high., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Proximal migration of double J stents after pediatric pyeloplasty is rare. Although retrograde removal of migrated stents is more common, the small calibre of the pediatric ureter may necessitate antegrade retrieval. Many techniques are described for the same in adults however, pediatric literature is sparse. We aim to describe the management of proximally displaced stents after pediatric pyeloplasty., Materials and Methods: This retrospective study included all children (<17 years age) who underwent retrieval of proximally displaced DJ stents after pyeloplasty between 2007 and 2019 at a single institution. The retrograde technique employed ureteroscopic retrieval with a grasper while in the antegrade technique, an access sheath was placed percutaneously into a calyx and Nephroscopic retrieval was performed., Results: There were 8 children (6 boys and 2 girls) of which 4 were infants. Median age was 3.5 (0.5-12) years and median follow-up was 7.5 (4-47) months. Two children had been referred with displaced stents after pyeloplasty from other centres. The incidence of proximal stent migration was 6/1644 (0.4%). Open pyeloplasty had been performed in seven while one child had undergone laparoscopic pyeloplasty. The lower coil of the migrated stent was in the renal pelvis in 6 (complete) and ureter in 2 (partial migration). Those with partial migration underwent successful ureteroscopic retrieval. Three infants required Antegrade stent removal while ureteroscopic retrieval was successful in an older child with complete stent migration. Nephrectomy for loss of function and redo pyeloplasty for pelvi-ureteric stricture was performed in one each. One child had self-limiting fever (Clavien 1) after stent removal. All had normal drainage on renogram after 6 months. The cause of proximal stent migration was likely to be an inadequate lower coil (<180°) in 5 children and a capacious pelvis with narrow ureter in one infant. The cause could not be ascertained in two children who were referred from other centres. The management algorithm for retrieval of proximally migrated DJ stents, is depicted in Fig. 3., Conclusions: Proximal migration of DJ stent after pyeloplasty is a rare complication which may be safely managed with a stepwise approach using both Antegrade and retrograde techniques. Accurate stent length, adequate distal coil and appropriate placement are essential to avoid stent migration., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Conventional platelet transfusion may not be adequate to deal with platelet transfusion refractoriness (PTR), and therefore human leukocyte antigen (HLA) or human platelet antigen (HPA) matched and platelet crossmatch compatible units are recommended. However, in developing countries, finding a unit that is HLA or HPA matched or platelet crossmatch poses a challenge. Hence, easier and cost-effective alternatives such as massive platelet transfusion and continuous platelet transfusion were attempted to manage bleeding in PTR. A 31-year-old male presented with acute myeloid leukemia relapse and chloroma in bladder underwent FLAG salvage chemotherapy. Despite almost daily platelet transfusion with single donor platelets (SDPs), patient presented with hematuria and low corrected count increment at 1 h and 24 h suggesting both immune and nonimmune refractoriness to platelet transfusion. The patient received SDP transfusion twice daily from day 19 to day 21 to maintain hemostasis. The patient had persistent hematuria, so massive platelet transfusion in the form of double adult doses of SDP given every 12 th hourly for three events. Despite these measures, there was persistent hematuria and refractoriness to platelet transfusion. As HLA or HPA matched or crossmatch compatible platelets were unavailable, continuous platelet transfusion was started for this patient from day 23 to day 28. After 4 days of continuous platelet transfusion, hematuria subsided. In resource-constrained clinical settings, continuous platelet transfusion can be an effective alternative to HLA/HPA-matched platelets in the management of PTR., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Transfusion Science.)

Objective: To examine the association of vitamin D insufficiency and risk of pregnancy-induced hypertension (PIH) among human immunodeficiency virus (HIV)-infected pregnant women., Study Design: This is a retrospective cohort study evaluating the impact of low maternal vitamin D levels on PIH and perinatal outcomes among HIV-infected pregnant women receiving care at an urban HIV center from 1991 to 2014., Results: A total of 366 pregnant women were included, of which 11% developed PIH. Lower levels of 25-hydroxyvitamin D (25(OH)D) and bioactive 1,25-dihydroxyvitamin D (1,25(OH) 2 D) were associated with increased HIV disease activity. 25(OH)D levels were not significantly associated with the incidence of PIH. Higher 1,25(OH) 2 D levels were associated with reduced incidence of PIH in univariate (odds ratio, OR: 0.87 [95% confidence interval, CI: 0.79-0.95], p  = 0.004) and multivariate (OR: 0.88 [95% CI: 0.80-0.97], p  = 0.010) analyses. No association was found between 25(OH)D levels and other obstetric outcomes. Lower 1,25(OH) 2 D levels were associated with group B Streptococcus colonization (OR: 0.92 [95% CI: 0.86-0.99]) and low birth weight (LBW) (OR: 0.90 [95% CI: 0.83-0.98]) on multivariate analysis. Mean 1,25(OH) 2 D levels were significantly lower in women with preterm delivery and LBW infants., Conclusion: Lower bioactive vitamin D levels are related to PIH in HIV-infected women. This association may be related to the coexistence of abnormal placental vitamin D metabolism and abnormal placental implantation., Competing Interests: None declared., (Thieme. All rights reserved.)

Schistosoma japonicum glutathione transferase (Sj26GST), an enzyme central to detoxification of electrophilic compounds in the parasite, is upregulated in response to drug treatment. Therefore, Sj26GST may serve as a potential therapeutic target for the treatment of schistosomiasis. Herewith, we describe the structural basis of inhibition of Sj26GST by ellagic acid (EA). Using 1-chloro-2,4-dinitrobenzene and reduced glutathione (GSH) as Sj26GST substrates, EA was shown to inhibit Sj26GST activity by 66 % with an IC 50 of 2.4 μM. Fluorescence spectroscopy showed that EA altered the polarity of the environment of intrinsic tryptophan and that EA decreased (in a dose-dependent manner) the interaction between Sj26GST and 8-Anilino-1-naphthalenesulfonate (ANS), which is a known GST H-site ligand. Thermodynamic studies indicated that the interaction between Sj26GST and EA is spontaneous (ΔG = -29.88 ± 0.07 kJ/mol), enthalpically-driven (ΔH = -9.48 ± 0.42 kJ/mol) with a favourable entropic change (ΔS = 20.40 ± 0.08 kJ/mol/K), and with a stoichiometry of four EA molecules bound per Sj26GST dimer. The 1.53 Å-resolution Sj26GST crystal structure (P 21 21 21 space group) complexed with GSH and EA shows that EA binds primarily at the dimer interface, stabilised largely by Van der Waal forces and H-bonding. Besides, EA bound near the H-site and less than 3.5 Å from the ε-NH 2 of the γ-glutamyl moiety of GSH, in each subunit., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Moyamoya disease (MMD) is a rare neurovascular disorder that is characterized by chronic progressive stenosis at the apices and bilateral occlusion of the intracranial internal carotid arteries. The occlusion is gradual in manner; multiple anastomoses are formed between the internal and external carotid arteries. The incidence of MMD has increased in Asian countries with a decline in Europe and United States., Case Description: The case report describes the specific clinical features and dental treatment in a 12-year-old male presenting with MMD with right-side hemiplegia. The patient presented with broken tooth in the upper front tooth region due to trauma. The dental treatment plan focused on providing restorative as well as preventive care to the patient., Clinical Significance: The patients with MMD have an increased risk of stroke development, which may be aggravated by pain or anxiety. It is necessary to avoid cerebral ischemic attacks caused by fluctuating BP and respiration. It becomes imperative to maintain normocapnia, normotension, and pain control during the procedure in order to prevent postoperative ischemic complications. Dental professionals must attain a complete knowledge of this disease and perform the dental treatment in pain and stress-free manner., How to Cite This Article: Goswami M, Pandian R, Sharma S. Moyamoya Disease-"A Puff of Smoke": A Rare Pediatric Case Report. Int J Clin Pediatr Dent 2020;13(5):566-568., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Electrospun nanofibrous Guar gum/PVA based scaffold matrix incorporated with standardized extracts of four traditional medicinal plants of wound healing repute namely - Acalypha indica (A.i), Aristolochia bracteolata (A.b), Lawsonia inermis (L.i) and Thespesia populnea (T.p) was developed. Combinatorial ratio optimization of the extracts subject to their impact on nanofibre morphology, thermal and swelling stability resulted in a 4:4:1:1 blend of A.i, A.b, T.p and L.i at 20% of the total weight of the polymer mix. Dermal toxicity studies on female wistar rats established the nontoxicity of the generated Scaffold/Dressing. Cutaneous wound healing ability of Mesenchymal Stem Cells (MSC's) is well characterized to amplify their delivery and efficacy at the wound site. Apart from ease of accessibility, increased immune modulation of Gingival MSC's is their clear merit relative to those conventionally sourced from adipose tissues and bone marrow. A population of cells were isolated from discarded sample of human gingiva, following standard procedures and characterized as per minimal criteria as described by International Society for Cellular Therapy's (ISCT). The Cytocompatibility and proliferation of GMSC's were evaluated by MTT and Calcein AM assay demonstrating the viability of the seeded GMSC's up to 6 days. In vivo efficacy of the scaffold with and without GMSC's showed complete restoration of the tissue with minimal scarring. This investigation thus generated an herb drug enriched nanofibrous mat as a dressing and also a skin like scaffold with GMSC's, integrating the biological and technological benefits of herbal medicine and stem cell therapy respectively for skin regenerative applications., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: CMV infection of the fetus or neonate can lead to devastating disease, and there are no effective prevention strategies to date. Vitamin D is a potent immunomodulator, supports antiviral immune responses, and plays an important role in placental immunity., Methods: Retrospective cohort study to evaluate the impact of low maternal vitamin D on congenital and early postnatal transmission of CMV among HIV-infected, non-breastfeeding women and their HIV exposed but negative infants from an urban HIV clinic. Vitamin D panel was performed on stored maternal plasma obtained near time of delivery. Infant CMV testing at 0-6 months included urine and oral cultures, and/or serum polymerase chain reaction testing., Results: Cohort included 340 mother-infant pairs (births 1991-2014). Among 38 infants (11%) with a CMV+ test between 0-6 months, 4.7% (14/300) had congenital CMV transmission (CMV+ test 0-3 weeks), and 7.6% (24/315) had peri/postnatal CMV (CMV+ test >3 weeks-6 months). Women with lower calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D, were more likely to have an infant with congenital (OR 12.2 [95% CI 1.61-92.2] P = 0.02) and peri/postnatal (OR 9.84 [95% CI 2.63-36.8] P = 0.0007) infections in multivariate analyses, independent of maternal HIV viral load and CD4 count., Conclusion: This study demonstrates an association between inadequate maternal calcitriol during pregnancy and increased congenital and early postnatal acquisition of CMV among non-breastfeeding women with HIV and their HIV negative infants., Competing Interests: RP is the salaried Director of Pan Laboratories, Irvine, CA. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Biofilm formation on antifouling coatings is a serious concern in seawater cooling systems and the maritime industry. A prolific biofilm forming strain ( Staphylococcus lentus ), possessing high tolerance (>1,000 µg ml -1 ) to dissolved copper ions (Cu ++ ) was isolated from titanium coupons exposed in the coastal waters of Kalpakkam, east coast of India. S. lentus formed increased biofilm ( p <  0.05) at 100 µg ml -1 of Cu ++ ions, when compared with the untreated control. To combat biofilm formation of this strain, the efficacy of copper oxide nanoparticles synthesized from copper nitrate by varying the concentrations of hexamine and cetyl trimethyl ammonium bromide (CTAB), was investigated. Complete (100%) inhibition of biofilm formation was observed with plain CuO NP (0.5 M hexamine, uncapped) at 1,000 µg ml -1 . Capping with CTAB, influenced the morphology and the purity of the synthesized CuO NPs but did not alter their surface charge. Capping reduced metal ion release from CuO NPs and their antibacterial and anti-biofilm property against S. lentus. Overall, uncapped CuO NPs were effective in controlling biofilm formation of S. lentus . Concurrent release of copper ions and contact mediated physical damage by CuO NPs offer a promising approach to tackle metal tolerant biofilm bacteria.

Research Question: Circulating soluble LH-HCG receptor (sLHCGR) is a first-trimester marker for screening pregnancy pathologies and predicts premature or multiple births before fertility treatment. Oestradiol per oocyte at ovulation induction predicts IVF treatment outcomes. We asked whether sLHCGR levels are stable during fertility treatment and whether, alone or with oestradiol, they could improve prediction of fertility treatment outcomes., Design: Serum sLHCGR, anti-Müllerian hormone [AMH] and oestradiol were measured in patients undergoing IVF. Antral follicle count before ovarian stimulation and oocyte yield were used to establish sLHCGR- oocyte ratio (SOR), sLHCGR- antral follicle ratio (SAR), oestradiol at trigger per oocyte (oestradiol-oocyte ratio [EOR]) and oestradiol at trigger per antral follicle (oestradiol-antral follicle ratio [EAR])., Results: The relatively stable sLHCGR was negatively related to AMH when oocyte yield was high. The sLHCGR levels were proportional (r = 0.49) to oestradiol at early cycle (day-3). Pregnancy and live birth were highest at low sLHCGR (≤1.0 pmol/ml) and SOR (≤ 0.1 pmol/ml/oocyte). A total of 86-89% of live births in IVF treatment were within the cut-off parameters of SAR and SOR (0.5 pmol/ml) and EAR and EOR (380 pg/ml). For failed pregnancy, age, SOR and EOR together had positive and negative predictive values of 0.841 and 0.703, respectively., Conclusions: sLHCGR levels are negatively related to AMH when oocyte yield is high. High early cycle sLHCGR is associated with elevated day-3 oestradiol. Low sLHCGR and SOR are indicators of increased clinical pregnancy and live birth rates. Patient age and SOR, combined with EOR, might improve prediction of IVF treatment outcomes., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Cognitive behaviour therapy (CBT) for Obsessive Compulsive Disorder (OCD) is therapist-intensive and prolonged making it less accessible to patients, particularly in resource-constrained situations. We examined the efficacy of a brief psychotherapeutic intervention as an adjunct to serotonin reuptake inhibitors (SRIs) in OCD., Method: We randomized 64 adult OCD patients stabilized on SRIs to either the 6-session brief family-based intervention (BFBI; n = 30) that included psychoeducation, exposure and response prevention and family intervention or to a control arm of relaxation exercises (RE). Assessments were conducted at baseline and at 1- and 3- months post-intervention. Primary outcome measure was response to treatment defined as ≥ 35% reduction in the Yale-Brown Obsessive Compulsive Scale total score relative to baseline score plus a Clinical Global Impression- Improvement rating of very much improved or much improved. Family accommodation and expressed emotions were also assessed., Results: At 3- month follow-up, the BFBI group responded better than the RE group (53% vs. 12%, p < 0.001). Illness severity, family accommodation and expressed emotion declined significantly over time in the BFBI group compared to the RE group. The BFBI (OR = 13.17, p < 0.001) and baseline illness severity (OR = 0.746, p < 0.011) predicted treatment response., Limitations: Sample size was small and follow-up duration was short. Control group had less time with the therapist although number of sessions was identical in both the groups., Conclusion: Briefer intervention is effective in treating OCD. Briefer and inclusive format of intervention has important implications for clinical practice in resource-constrained circumstances., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Implementation of Au nanoparticles (NPs) is a subject for frontier plasmonic research due to its fascinating optical properties. Herein, the present study deals with plasmonic assisted emission properties of Au NPs-vertical graphene (VG) hybrid nanostructures. The influence of effective polarizability of Au NPs on the surface enhanced Raman scattering and luminescence properties is investigated. In addition, a remarkable infra-red emission in the hybrid nanostructures is observed and interpreted on the basis of intra-band transitions in Au NPs. The flake-like nanoporous VG structure is invoked for the generation of additional confined photons to impart additional momentum and a gradient of confined excitation energy towards initiating the intra-band transitions of Au NPs. Integrating Au plasmonic materials in three-dimensional VG nanostructures enhances the light-matter interactions. The present study provides a new adaptable plasmonic assisted pathway for optoelectronic and sensing applications.

We demonstrate controlled fabrication of porous Si (PS) and vertically aligned silicon nanowires array starting from bulk silicon wafer by simple chemical etching method, and the underlying mechanism of nanostructure formation is presented. Silicon-oxidation rate and the electron-scavenging rate from metal catalysis play a vital role in determining the morphology of Si nanostructures. The size of Ag catalyst is found to influence the Si oxidation rate. Tunable morphologies from irregular porous to regular nanowire structure could be tailored by controlling the size of Ag nanoparticles and H 2 O 2 concentration. Ag nanoparticles of size around 30 nm resulted in irregular porous structures, whereas discontinuous Ag film yielded nanowire structures. The depth of the porous Si structures and the aspect ratio of Si nanowires depend on H 2 O 2 concentration. For a fixed etching time, the depth of the porous structures increases on increasing the H 2 O 2 concentration. By varying the H 2 O 2 concentration, the surface porosity and aspect ratio of the nanowires were controlled. Controlling the Ag catalyst size critically affects the morphology of the etched Si nanostructures. H 2 O 2 concentration decides the degree of porosity of porous silicon, dimensions and surface porosity of silicon nanowires, and etch depth. The mechanisms of the size- and H 2 O 2 -concentration-dependent dissociation of Ag and the formation of porous silicon and silicon nanowire are described in detail., Competing Interests: The authors declare no competing financial interest.

Tailoring the surface properties by varying the chemistry and roughness could be of interest for self-cleaning applications. We demonstrate the transformation of hydrophobic ZnO Nano rod (NR) array into superhydrophobic nature by changing the local chemical state and without altering the surface roughness by swift heavy ion (SHI) irradiation. The aligned ZnO NR arrays were irradiated using 150 MeV Ag ions with different fluences from 5E10 to 3E12 ions/cm 2 . The observed static water contact angles of ZnO NRs samples were 103° ± 3°, 152° ± 4°,161° ± 3°, 164° ± 2°, 167° ± 2°,154 ± 3° and 151° ± 2° for the pristine, ion fluencies of 1E11, 3E11, 5E11, 7E11, 1E12 and 3E12 ions cm -2 , respectively. The change in local surface chemistry via formation of surface oxygen related defects due to electronic excitations induced by ion irradiation determine the water dewetting properties. It is found that surface oxygen related defects could be tuned by varying the fluence of the SHIs. Durability tests show that the SHI induced surface oxygen-deficient ZnO NRs have the stable superhydrophobic behavior for more than a year.

Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44 high /CD147 high cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.

Aims: One of the most common fungal infections infecting humans is Candidiasis. Belonging to the group of opportunistic infections, it often affects individuals with various debilitating diseases. Fluconazole and clotrimazole are two of the commonly used anti-fungal agents for the treatment of oral candidiasis. Hence, we planned this study to evaluate the effectiveness of fluconazole and clotrimazole in the treatment of patients suffering from candidiasis., Materials and Methods: A total of 180 participants were enrolled in the present study. All the patients of candidiasis were divided broadly into two study groups. Group I included patients who were treated with fluconazole mouthrinse whereas group II included patients who were treated with clotrimazole mouth paint. Grading of patient discomfort was done as noted from readings given by the patients. Specimen was collection by a swab from the lesional area of the oral cavity from the patients and were incubated in Sabouraud's dextrose agar medium and assessed. All the patients were treated with medication as give to their respective groups. Patients were recalled as assessed. All the readings were recorded and analyzed., Results: For group I patients, the fungal eradication was 89.5%, whereas for group II patients, the fungal eradication was 86.7%. No significant results were obtained while comparing the mycological eradiation in patients of the two study groups., Conclusion: Approximately similar effectiveness in terms of treatment was noted with fluconazole and clotrimazole in treating patients with candidiasis., Competing Interests: There are no conflicts of interest.

Alkaptonuria is a rare autosomal recessive disorder of tyrosine metabolism. Deficiency of homogentisate 1,2 dioxygenase results in accumulation of oxidized homogentisic acid in the connective tissues of the skin, eyes and ears, musculoskeletal system, and cardiac valves, and in urolithiasis. Excretion of excessive homogentisic acid in urine causes dark-colored urine on exposure to air. We present a case of alkaptonuria with multiple system involvement, who presented with lower urinary tract symptoms secondary to vesical and prostatic calculi., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Chemoresistance leading to disease relapse is one of the major challenges to improve outcome in head and neck cancers. Cancer Stem Cells (CSCs) are increasingly being implicated in chemotherapy resistance, this study investigates the correlation between CSC behavior and acquired drug resistance in in vitro cell line models. Cell lines resistant to Cisplatin (Cal-27 CisR, Hep-2 CisR) and 5FU (Cal-27 5FUR) with high Resistance Indices (RI) were generated (RI ≥ 3) by short-term treatment of head and neck squamous cell carcinoma (HNSCC) cell lines with chemotherapeutic drugs (Cisplatin, Docetaxel, 5FU), using a dose-incremental strategy. The cell lines (Cal-27 DoxR, Hep-2 DoxR, Hep-2 5FUR) that showed low RI, nevertheless had a high cross resistance to Cisplatin/5FU (P < 0.05). Cal-27 CisR and DoxR showed 12-14% enrichment of CD44+ cells, while CisR/5FUR showed 4-6% increase in ALDH1A1+ cells as compared to parental cells (P < 0.05). Increased expression of stem cell markers (CD44, CD133, NOTCH1, ALDH1A1, OCT4, SOX2) in these cell lines, correlated with enhanced spheroid/colony formation, migratory potential, and increased in vivo tumor burden (P < 0.05). Inhibition of ALDH1A1 in Cal-27 CisR led to down regulation of the CSC markers, reduction in migratory, self-renewal and tumorigenic potential (P < 0.05) accompanied by an induction of sensitivity to Cisplatin (P < 0.05). Further, ex vivo treatment of explants (n = 4) from HNSCC patients with the inhibitor (NCT-501) in combination with Cisplatin showed a significant decrease in proliferating cells as compared to individual treatment (P = 0.001). This study hence suggests an ALDH1A1-driven, CSC-mediated mechanism in acquired drug resistance of HNSCC, which may have therapeutic implications. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)