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BACKGROUND Ventriculomegaly is common in aneurysmal subarachnoid haemorrhage (aSAH). An imaging measure to predict the need for cerebrospinal fluid (CSF) diversion may be useful. The bicaudate index (BCI) has been previously applied to aSAH. Our aim was to derive and test a threshold BCI above which CSF diversion may be required. METHODS Review of prospective registry. The derivation group (2009-2015) included WFNS grade 1-2 aSAH patients who deteriorated clinically, had a repeat CT brain and underwent CSF diversion. BCI was measured on post-deterioration CTs and the lower limit of the 95% confidence interval (95%CI) was the hydrocephalus threshold. In a separate test group (2016), in WFNS ≥ 2 patients, we compared BCI on diagnostic CTs with CSF diversion within 24 hours. RESULTS The derivation group (n = 62) received an external ventricular (n = 57, 92%) or lumbar drain (n = 5, 8%). Mean post-deterioration BCI was 0.19 (95%CI 0.17-0.22) for age ≤49 years, 0.22 (95%CI 0.20-0.23) for age 50-64 years and 0.24 (95%CI 0.22-0.27) for age ≥65 years. Hydrocephalus thresholds were therefore 0.17, 0.20 and 0.22, respectively. In the test group (n = 105), there was no significant difference in BCI on the diagnostic CT between good and poor grade patients aged ≤49 years (p = 0.31) and ≥65 years (p = 0.96). 30/66 WFNS ≥ 2 patients underwent CSF diversion, although only 15/30 (50%) exceeded BCI thresholds for hydrocephalus. CONCLUSION A significant proportion of aSAH patients may undergo CSF diversion without objective evidence of hydrocephalus. Our threshold values require further testing but may provide an objective measure to aid clinical decision making in aSAH.

To achieve carbon-neutral energy vectors, researchers have investigated various sulfur-based thermochemical cycles. The sulfur–iodine cycle has emerged as a cost-effective global process with massi...

The emergence of COVID-19 took the world by shock in December 2019, starting from Wuhan, China and swiftly spreading across the globe. The number of COVID-19 cases continues to rise which is a global burden on the health care system worldwide. Efforts are continuing to come up with a solution either to develop a small molecular inhibitor or vaccine, but still no success. In the fight against SARS-CoV-2, targeting a different protein of the SARS-CoV-2 is the need of the hour to impede and relinquish the current pandemic. Therefore, in this study, computational modelling and simulation approaches are used to target the N-terminal domain of the phosphor-nucleoprotein (RNA binding protein), which is primarily responsible for binding and packing the viral genome to get ribonucleoprotein complex (RNP). Our multi-step drug screening approach shortlisted potential drugs. These top hits were confirmed by re-docking which revealed that the interacting molecules block the key residues i.e. Thr57, His59, Ser105, Arg107, and Arg177 and thus ultimately block the NTD from RNA recognition. Furthermore, the activity of the top four hits was also confirmed by using molecular dynamics simulation and free energy calculation. Our analysis suggests that these top hits possess strong inhibitory properties and should be tested experimentally. In conclusion, we hope these top hits would abrogate the binding of RNA and the NTD of the SARS-CoV-2, which might be helpful to combat COVID-19.Communicated by Ramaswamy H. Sarma.

This study uses the conservation of resource theory to examine the effects of psychopathic leadership on employee career satisfaction and turnover intention via self-efficacy. This study also exami...

The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities. Communicated by Ramaswamy H. Sarma

Pyrazinamidase (PZase) is a member of Fe-dependent amidohydrolases that activates pyrazinamide (PZA) into active pyrazinoic acid (POA). PZA, a nicotinamide analogue, is an essential first-line drug...

Helicobacter pylori (H. pylori) is one of the most extensively studied Gram-negative bacteria due to its implication in gastric cancer. The oncogenicity of H. pylori is associated with cytotoxin-associated gene A (CagA), which is injected into epithelial cells lining the stomach. Both the C- and N-termini of CagA are involved in the interaction with several host proteins, thereby disrupting vital cellular functions, such as cell adhesion, cell cycle, intracellular signal transduction, and cytoskeletal structure. The N-terminus of CagA interacts with the tumor-suppressing protein, apoptosis-stimulating protein of p53 (ASPP2), subsequently disrupting the apoptotic function of tumor suppressor gene p53. Here, we present the in-depth molecular dynamic mechanism of the CagA–ASPP2 interaction and highlight hot-spot residues through in silico mutagenesis. Our findings are in agreement with previous studies and further suggest other residues that are crucial for the CagA–ASPP2 interaction. Furthermore, the ASPP2-binding pocket possesses potential druggability and could be engaged by decoy peptides, identified through a machine-learning system and suggested in this study. The binding affinities of these peptides with CagA were monitored through extensive computational procedures and reported herein. While CagA is crucial for the oncogenicity of H. pylori, our designed peptides possess the potential to inhibit CagA and restore the tumor suppressor function of ASPP2.

The present research was conducted to explore the impact of alternative organic amendments on physicochemical properties of soil and their critical value for kiwi seedlings growth. The experiment was laid out in completely randomized design with 3 replications and 20 seedlings per replication. The highest pH (8.0) was recorded in T3 (compost + silt) and the highest electrical conductivity (EC) of 5.91 dS/m, organic matter (24.11%), organic carbon (13.99%), organic nitrogen (1.51%) were recorded in T8 (compost + peat moss (PM) + leaf manure) and the highest soil porosity (SP) (45.95%) and lowest bulk density (0.67) were recorded in T4 (PM + garden soil (GS)). EC higher than 1.99 and SP (45.95%) were found critical and adversely affected seedling survival. The highest plant height (103 and 93 cm), number of leaves (23 and 20), number of first-order lateral roots (NFLRM) (9 and 8.5), whole seedling fresh mass (75 and 72 g), fresh root mass (FRM) (35 and 35 g), shoot fresh mass (46 and 40 g), root collar diameter (RCD) (13 and 12 mm), and shoot diameter (10 and 9 mm) were recorded in T5 (compost + GS) and T7 (compost + PM + GS). Strong and positive correlations were observed among NFLRP, RFM, and RCD (R² = 0.89 and 0.96) and all the above-ground seedling traits (R² = 0.86–0.98). It is concluded that compost is a good soil amendment for producing good quality graftable kiwi seedlings and evaluation of seedling root system architecture could be used to predict the potential and success of seedlings in the field.

TiO2 has received tremendous attention owing to its potential applications in the field of photocatalysis for solar fuel production and environmental remediation. This review mainly describes various modification strategies and potential applications of TiO2 in efficient photocatalysis. In past few years, various strategies have been developed to improve the photocatalytic performance of TiO2, including noble metal deposition, elemental doping, inorganic acids modification, heterojunctions with other semiconductors, dye sensitization and metal ion implantation. The enhanced photocatalytic activities of TiO2-based material for CO2 conversion, water splitting and pollutants degradation are highlighted in this review.

The inhibitory efficiency of anionic copolymers and the effect of the biocides sodium hypochlorite, glutaraldehyde, and tris(hydroxymethyl)nitromethane on the precipitation behavior of calcium fluoride (CaF2) were studied. The efficiency of polymeric inhibitors was traced from conductivity measurements by using half-life (t1/2) method. X-ray diffraction parameters have been measured for calcium fluoride scale minerals. An anionic copolymer (K-798) acts as one of the best inhibitors for the precipitation process of the calcium fluoride in water as compared to K-775. It is assigned to the fact that the copolymer (K-798) contains both sulfonic acid and sulfonated styrene groups while the polymer (K-775) having only the sulfonic acid group. It was further observed that the biocides have no appreciable effect on the performance of the anionic polymeric inhibitors.

The physicochemical investigations on the associative, micellar, and thermodynamic properties of a diblock (PEO)62-b-(PBO)33 copolymer in aqueous medium and its interaction with ionic surfactants were carried out by using surface tensiometry, laser light scattering, and steady-state fluorescence spectroscopy. Surface tension and fluorescence measurements were used to find out the critical micelle concentration (CMC) and related thermodynamic parameters of micellization copolymer at various temperatures. The data from dynamic light scattering (DLS) were helpful to obtain the values of hydrodynamic radii (Rh), volume (υh), and hydrodynamic expansion parameter (δh) of the copolymer micelle. Likewise, the measurements from static light scattering (SLS) were employed to determine weight-average molar (Mw), association number (Nw), thermodynamic radius (Rt), thermodynamic volume (υt), anhydrous volume (υa), and thermodynamic expansion parameter (δt) of the copolymer micelles in the temperature range of 20–50°C....

Recent development in dispersion science and technology demands block copolymers with a variable block length and composition. To highlight that purpose, the surface active, associative, colloidal, and thermodynamic behavior of three diblock copolymers having different hydrophilic to hydrophobic ratio is reported here. Using surface tension and light scattering measurements, the micellization and adsorption behavior of polyoxyethylene and polyoxybutylene diblock copolymers of the type EmBn have been analyzed. Critical micelle concentration (CMC) and related thermodynamic parameters like free energy (ΔGmic), enthalpy (ΔHmic), and entropy (ΔSmic) of micellization were calculated from CMC value using the closed association model. Likewise, the surface active parameters, like surface excess concentration (Γ2), area per molecule (A2), and thermodynamic parameters such as free energy (ΔGads), enthalpy (ΔHads), and entropy (ΔSads) of adsorption of polymer at the air/water interface, were also calculated at vario...

A novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the determination of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) in human plasma using atorvastatin as internal standard. The method was validated according to international guidelines. The analytical column used was HiChrom® C18 (150 × 3.0 mm, 3 µm; Reading, UK) and the mobile phase comprised of 0.1% formic acid in acetonitrile and 0.1% formic acid in water (70:30 v/v), pumped at 300 µL/min. The precipitation of plasma proteins and extraction of analytes were carried out by a simple one-step procedure using acetonitrile. The calibration curves were linear (r2 = 0.999) over the concentration range of 0.2–20 ng/mL for rosuva and 0.1–10 ng/mL for NDM-rosuva. The lower limits of detection and quantification for rosuva were 0.1 and 0.2 ng/mL, whereas for NDM-rosuva, these were 0.03 and 0.1 ng/mL, respectively. The intra- and inter-day precisions expressed as relative standard deviation...

A method was developed for the determination of omeprazole, 5-hydroxy-omeprazole, and omeprazole-sulphone in human plasma. The mobile phase with 0.1% formic acid in acetonitrile and 0.1% formic acid in water (40/60 v/v) was used successfully for the first time for the analysis of these analytes. Analysis was carried out using Hichrom RP18 (150 × 3.0 mm, 3 µm. UK) column interfaced with a LTQ Orbitrap mass spectrometer. The calibration range for omeprazole and omeprazole sulphone was 0.002–1 µg/mL, whereas, for 5-hydroxy omeprazole was 0.005–1 µg/mL. The extracted ion ranges ([M + H]+) were; m/z 346.12–346.13 for omeprazole, 362.11–362.12 for 5-hydroxy-omeprazole, and omeprazole-sulphone and 384.07–384.09 for pantoprazole. The regression equation for omeprazole was 0.071x + 0.445, for 5-hydroxy omeprazole was y = 0.08x + 0.017 and for omeprazole sulphone y = 0.007x + 0.05. This method was successfully applied for the determination of pharmacokinetic parameters of omeprazole and its metabolites in human vol...

Multiresponsive poly(N-isopropylacrylamide-co-methacrylic acid) microgels were synthesized by precipitation polymerization in aqueous medium. Then silver-poly(N-isopropylacrylamide-co-methacrylic acid) hybrid microgels were prepared by in-situ reduction of silver ions. Formation of microgels was confirmed by Fourier transform infrared spectroscopic analysis. pH and temperature sensitivity of microgel was studied by dynamic light scattering. Hydrodynamic radius of microgels decreases with increase in temperature at pH 8.20 and show volume phase transition temperature around 45°C. At pH 2.65, hydrodynamic radius decreases with increase in temperatures upto 35°C but further increase in temperature causes aggregation and microgel becomes unstable due to increase of hydrophobicity. With increase in pH of medium, the hydrodynamic radius of microgels increases sigmoidally. Formation of silver nanoparticles inside microgel and pH dependence of surface plasmon resonance wavelength of the hybrid microgels were inve...

The interaction between diblock copolymer with ionic surfactants in aqueous solution were studied employing surface tensiometery, electrical conductivity, steady-state fluorescence spectroscopy and dynamic laser light scattering at 303 K. Surface tension measurements were used to determine critical micelle concentration (CMC) and, thereby, its free energy of micellization (ΔGm), free energy of adsorption (ΔGads), surface excess concentration (Γ), and minimum area per molecule (A). The negative values of (ΔGm) both in case of SDS and CTAB confirmed the spontaneity of the processes. Conductivity measurements were used to determine critical micelle concentration (CMC), critical aggregation concentration (CAC), polymer saturation point (PSP), degree of ionization (α), and counterion binding (β). Addition of polymers could effectively reduce the CMC value of surfactants and, thus increase the detergency. Dynamic light scattering experiments were performed to check the changes in physiochemical properties of th...

The aqueous solutions of three triblock copolymers based on polyoxyethylene and polyoxybutylene of the type EmB10Em have been analyzed by surface tension measurements. Surface activity of these triblock copolymers was studied by measuring surface parameters, like surface excess concentration, Γ2, area per molecule of polymer and standard Gibb's free energy of adsorption, ΔoGads, at various temperatures in the range of 20 to 50°C. The Effect of block length of hydrophilic portion of triblock copolymers on surface activity was investigated in this work. Miceller behavior of these triblock copolymers was also investigated using above technique. Critical micelle concentration (CMC) was determined from the plot of surface tension versus log of concentration in the range of temperature of 20–50°C. Thermodynamic parameters, standard free energy of micellization, ΔoGmic, standard enthalpy of micellization, ΔoHmic, and standard entropy of micellization, ΔoSmic were calculated from CMC value using closed associatio...

Stability of pharmaceutical products is the ultimate objective of the pharmaceutical sector. Preservatives are the essential and effective part of all types of Syrup and suspension formulations. A fast reversed-phase high performance liquid chromatography method is developed for the determination of sodium benzoate (SB) and alkyl esters of Para hydroxyl benzoic acid such as ethyl paraben (EP), methyl paraben (MP), and propyl paraben (PP) in marketed analgesic suspensions collected from different sources. Complete separation of all the analytes was achieved on an Hypercil C18 (256 mm × 6.4 mm; 5 µm) column using acetonitrile and acetate buffer (pH 5) in the ratio of (35:65, v/v) as the mobile phase pumped at a flow rate of 1.5 mL/min in isocratic mode. Under the optimized experiment conditions, separation of the analytes was achieved in less the 10 min. Efficacy of the preservatives is determined in the prepared suspensions using the identified strains of bacteria, that is, Escherichia coli ATCC (8739), Ps...

The interaction of nonionic diblock copolymer poly(ethylene oxide butylene oxide) (E62B22) with a cationic surfactant cetyl trimethyl ammonium bromide (CTAB) and anionic surfactant sodium dodecyl sulphate (SDS) were studied using surface tension, conductivity, and dynamic laser light scattering techniques. Surface tension measurements were used to determine critical micelle concentration and thereby its free energy of adsorption (ΔGads), free energy of micellization (ΔGm), surface excess concentration (Γ), and minimum area per molecule (A). Conductivity measurements were used to determine critical micelle concentration (CMC) critical aggregation concentration (CAC) at different temperatures, enthalpy of micellization (ΔHm), free energy of micellization and entropy of micellization (ΔSm). Changes in physicochemical properties of the micellized block copolymer were studied by using dynamic laser light scattering. The effect of surfactant on the size and properties of block copolymer has also been discussed.

The interactions of triblock copolymers (TBP) with ionic surfactants were studied employing surface tensiometry, electrical conductivity, steady-state fluorescence (SSF), and dynamic light scattering (DLS) techniques. An increasing trend in the critical micelle concentration (CMC) of SDS/CTAB in the presence of triblock copolymers was observed especially at higher polymer to surfactant ratio. The delay in the CMC of surfactants was more pronounced in the presence of E48B10E48 possibly due to its less hydrophobic nature. The negative values of free energy of micellization (ΔGm) both in case of SDS and CTAB confirmed the spontaneity of the processes. The aggregation number (Nagg) and hydrodynamic radius (Rh) of polymer/surfactant mixed systems were determined by SSF and DLS. The suppression of the surfactant micelle size in the presence of TBP was confirmed by SSF and DLS studies.

A simple, rapid, and sensitive high performance liquid chromatographic method with UV detection has been developed for the quantification of clopidogrel in human plasma and pharmaceutical dosage form using diclofenac sodium as an internal standard and validated according to standard guidelines. The separation of clopidogrel and diclofenac sodium was achieved using Hypersil BDS RP18 (250 × 4.6 mm, 5 µm) at a column oven temperature of 35°C. The methanol and phosphoric acid 25 mM (80:20, v/v) (pH 3.0), used as a mobile phase in the isocratic mode was pumped at a flow rate of 1.2 mL min−1 and eluents were monitored at a wavelength of 220 nm. The retention times for diclofenac sodium and clopidogrel were 4.15 and 4.62 min, respectively. Extraction of drug from plasma was carried out with diethyl ether. The limit of detection (LOD) was 2.0 ng mL−1, while limit of quantification (LOQ) was 5.0 ng mL−1. The calibration curves were linear (r2 = 0.999) over the concentration range of 0.005 to 5.0 µg mL−1 for both s...

Background: Exit exams for completion of surgical training are demanding and have relatively low pass rates with many candidates requiring multiple attempts. Aim: To establish a new, clinically based exam preparation course, utilising multi-source feedback, to identify candidates at risk of failure and improve pass rates. Methods: We describe the process of establishing a new, unique, clinically based exam preparation course incorporating multisource feedback from examiners, patients, nurses and other trainees. We present the course results as well as the exam results for each candidate and analyse the results of the multi-source feedback. Results: Nine candidates have so far successfully completed both the preparation course and the FRCS(Plast) exam. Success in the exam preparation course accurately predicts success in the FRCS(Plast) exam. Nursing staff and patients tend to give higher scores than examiners and trainees. The majority of marginal failures from the course went on to pass the exam, indicating that the course allows candidates to successfully address weaknesses identified on the course. Conclusion: A clinically based exam preparation course utilising multi-source feedback allows identification of candidates at risk of failing a surgical training exit exam and allows targeted training in order to maximise pass rates.

Micro RNAs (miRNAs) have emerged as an important class of gene expression regulators controlling development, growth and metabolism. These short RNA molecules are 20–24 nucleotides in length and act post-transcriptionally to regulate the cleavage or translation of specific mRNA targets. In the model legume Medicago truncatula, we have recently reported identification of 100 novel and 27 conserved miRNAs in root apexes and nodules. Statistical analysis on sequencing results revealed specific miRNA isoforms for the same family (up to 3 mismatches) showing contrasting expression patterns between these tissues. Here, we report the cleavage of a non-conserved target of miR156 in root apexes complementary to a differentially expressed miR156 isoform. This suggests that changes in the abundance of miRNA isoforms may have functional consequences on the post-transcriptional regulation of new mRNA targets in different organs.