Antiplasmodial and Insecticidal Activities of Third-Generation Ivermectin Hybrids.

Preclinical and/or clinical studies have demonstrated the potential of Ivermectin (IVM) for malaria control. In order to improve its antiplasmodial activity and build on previous knowledge, we have designed a third generation of hybrid molecules in which selected pharmacophores were appended to the IVM macrolide, while retaining one or both sugar moieties at the C-13 position. Moreover, we synthesized IVM hybrids that contain structural features of potent IVM metabolites.

PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia.

Objective: The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management.

Methods: Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration.

High HIV prevalence in gestational trophoblastic neoplasia patients.

Objective: To assess the HIV prevalence in patients diagnosed with gestational trophoblastic neoplasia (GTN).

Design: A retrospective single centre cohort study.

Methods: A database from the Sheffield Trophoblastic Disease Centre (STDC), Sheffield, UK was searched between 1st January 2015 and 31st December 2021.

Size economy and first hyperpolarizability: synthesis and nonlinear optical behavior of ferrocene-based donor-acceptor chromophores lacking π-linkers.

The question of size economy in the design of chromophores for nonlinear optics is addressed in this investigation. We have synthesized directly linked donor-acceptor dyads, which lack a π-conjugated linker, the presence of which is usually considered obligatory in materials designed for nonlinear optics. Correlating linear optical data, electrochemical data, computational data and hyper Rayleigh scattering (HRS) data on ferrocene (Fc) based dyads, we demonstrate that the first hyperpolarizability of such size economical chromophores is significantly better compared to that of Fc based, traditional, larger, donor-π-acceptor chromophores.

Bis-cyanostilbene based fluorescent materials: A rational design of AIE active probe for hypochlorite sensing.

In the present investigation cyanostilbene based molecular probes, PCS and PCO, bearing N,N-dimethylthiocarbamate and N,N-dimethylcarbamoyal groups, respectively, have been synthesised. These probes exhibit AIEE activity in their aggregated state in the mixed solvent system of THF: HO by way of turning on their emission, which has also been observed in powder, neat thin films and hybrid polymer films. While the probe PCO is silent to ClO, PCS exhibits a significant response towards ClO rationalised on the basis of HOCl specific oxidation of thiocarbamate, which is also extended to detect ClO in water samples.

Positive and Neutral Needleless Connectors: A Comparative Study of Central-line Associated Bloodstream Infection, Occlusion, and Bacterial Contamination of the Connector Lumen.

A pragmatic, multiphase prospective quality improvement initiative was performed to determine whether a positive displacement connector (PD) causes reduction of central line-associated bloodstream infection (CLABSI), occlusion, and catheter hub colonization when compared with a neutral displacement connector with alcohol disinfecting cap (AC). Patients with an active central vascular access device (CVAD) were enrolled March 2018 to February 2019 (P2) and compared to the prior year (P1). Two hospitals were randomized to use PD without AC (Hospital A) and with AC (Hospital B).

Julolidine-hydrazone based chemosensor for detection of Zn: Fluorescent in-situ formed Zn complex discriminates PPi from ADP and ATP.

In the present investigation, we have designed and synthesised Zn sensitive Julolidine-hydrazone (JSB) based chemosensor, which crystallised in a monoclinic crystal system with P21/c space group. The bare JSB was nonemissive, but in the presence of Zn ions in solution it showed emission, ascribed to the chelation enhanced emission process, which is also utilised to detect Zn in water samples. Comparing the chromaticity coordinates deduced from the emission colors of the JSB-Zn in solution, powder and hybrid polymer thin film, using CIE (Commission Internationale de I'Eclairage 1931) chromaticity diagram, it was found that compared to the emission of the solution, the emission of the powder was red shifted, while that of the thin film was blue shifted.

Julolidine based red emitting ESIPT/AIE active material showing luminescence beyond excimer emission: An "on-off" emission response to Cu.

A new julolidine-fluorene based excited state intramolecular proton transfer (ESIPT)/aggregate induced emission (AIE) active Schiff-base (JDF) has been synthesized and evaluated for its photophysical properties in solution and aggregated/solid states. The correlation between the emission behavior and the solid state crystal packing structure revealed the interplay of ESIPT coupled excimer reaction occurring in the solid state, which is one of the rare examples reported so far. For a comprehensive comparison, we synthesized a non-ESIPT methyl derivative (JDF-Me) of JDF capable of showing excimer emission only in the solid state.

Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia.

Background: Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue.

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO.

Synthesis and Nonlinear Optical Behavior of Thermally Stable Chromophores Based on 9,9-Dimethyl-9-fluoren-2-amine: Improving Intrinsic Hyperpolarizability through Modulation of "Push-Pull".

Improvement in the first hyperpolarizability (β) as well as intrinsic hyperpolarizability (β) of chromophores based on 9,9-dimethyl-9-fluoren-2-amine through modulation of the conjugation pathway is described. A series of six novel chromophores with "linear" conjugation showed significant enhancement of β as well as β compared to the counterparts lacking a "linear" conjugation but having an identical combination of donor, acceptor, and the intervening π-conjugated linker. The hyperpolarizability (β as well as β) values of the new series measured using hyper-Rayleigh scattering exceeded the apparent limit set by the latter set of fluorene-based chromophores.

Towards hospital-on-chip supported by 2D MXenes-based 5 generation intelligent biosensors.

Existing public health emergencies due to fatal/infectious diseases such as coronavirus disease (COVID-19) and monkeypox have raised the paradigm of 5 generation portable intelligent and multifunctional biosensors embedded on a single chip. The state-of-the-art 5 generation biosensors are concerned with integrating advanced functional materials with controllable physicochemical attributes and optimal machine processability. In this direction, 2D metal carbides and nitrides (MXenes), owing to their enhanced effective surface area, tunable physicochemical properties, and rich surface functionalities, have shown promising performances in biosensing flatlands.

Analyte Detection: A Decade of Progress in the Development of Optical/Fluorescent Sensing Probes.

The development of selective and sensitive chemical sensors capable of detecting metal ions, anions, neutral species, explosives and hazardous substances, selectively and sensitively has attracted considerable interest of various research groups. The presence of such analytes within the permissible limits is often beneficial, but the excess amounts may lead to lethal effects to both the environment as well as the living organisms. Owing to the toxicity of the heavy metal ions, toxic anions and nitro-aromatics which are main constituents of explosives, the timely detection of these materials is most desirable to ensure safety and security of the mankind.

Pore-scale visualization of hydrogen storage in a sandstone at subsurface pressure and temperature conditions: Trapping, dissolution and wettability.

Hypothesis: Underground hydrogen (H) storage is a potentially viable solution for large-scale cyclic H storage; however, the behavior of H at subsurface pressure and temperature conditions is poorly known. This work investigates if the pore-scale displacement processes in H-brine systems in a porous sandstone can be sufficiently well defined to enable effective and economic storage operations. In particular, this study investigates trapping, dissolution, and wettability of H-brine systems at the pore-scale, at conditions that are realistic for subsurface H storage.

Fluorene-Chloroquine Hybrids: Synthesis, in vitro Antiplasmodial Activity, and Inhibition of Heme Detoxification Machinery of Plasmodium falciparum.

Fluorene-chloroquine hybrids have been identified as a new promising class of antiplasmodial agents. The most active compound 9 d exhibited good in vitro antiplasmodial activity against a chloroquine-sensitive NF54 strain of the human malaria parasite Plasmodium falciparum with an IC value of 139 nM. UV-visible absorption, FTIR spectral and H NMR titration data corroborated the binding of 9 d to monomeric and μ-oxodimeric heme as well as inhibition of β-hematin formation, which collectively supported the inhibition of heme detoxification machinery in P.

Evaluation of the Dynamic Interfacial Tension between Viscoelastic Surfactant Solutions and Oil Using Porous Micromodels.

Interfacial tension (IFT) is a crucial parameter in many natural and industrial processes, such as enhanced oil recovery and subsurface energy storage. IFT determines how easy the fluids can pass through pore throats and hence will decide how much residual fluids will be left behind. Here, we use a porous glass micromodel to investigate the dynamic IFT between oil and Armovis viscoelastic surfactant (VES) solution based on the concept of drop deformation while passing through a pore throat.

Thiazolothiazole based donor-π-acceptor fluorophore: Protonation/deprotonation triggered molecular switch, sensing and bio-imaging applications.

Stimuli modulated photophysical properties of a new asymmetric multifunctional molecular probe, 2-(pyren-1-yl)-5-(pyridin-4-yl)thiazolo [5,4-d]thiazole (PYTZ-P) bearing electron-rich pyrene and electron-deficient pyridine units linked through a π-conjugated thiazolo [5,4-d]thiazole (TTz) bridge are reported. Its sensitivity towards protons (TFA) in solution is manifested in the form of bathochromically shifted emission that spreads all over the visible region, and is related to the increased acceptor strength of pyridine upon protonation and subsequent enhanced magnitude of intramolecular charge-transfer in the probe. Similar modulation of the luminescence behaviour of the probe was also observed in the solid state.

Second-order nonlinear polarizability of "Push-Pull" chromophores. A decade of progress in donor-π-acceptor materials.

Fine tuning and switching of nonlinear optical response of ferrocene chromophores has been an area of considerable significance as evidenced by a large number of reports in the current literature. In this personal account, we present linear/nonlinear behavior and structure-activity relationships of several classes of donor-π-acceptor designs using organometallic and organic materials, developed by our research group during the last decade. The results especially the electronic absorption spectral and the hyper-Rayleigh scattering have been supported by theoretical calculations.

Quinoline-Dihydropyrimidin-2(1H)-one Hybrids: Synthesis, Biological Activity, and Mechanistic Studies.

A novel class of quinoline-dihydropyrimidin-2(1H)-one (DHPM) hybrids was synthesized and in vitro antiplasmodial activity was evaluated against chloroquine sensitive (D10) and chloroquine resistant (Dd2) strains of Plasmodium falciparum, the human malaria parasite. The antiplasmodial activity was compared to previously reported DHPM based molecular hybrids. Dual mode of antiplasmodial action of the most active member has been evaluated through heme binding study and in silico docking in the active site of dihydrofolate enzymes (wild-type as well as mutant).

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids.

With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM.

New type of pore-snap-off and displacement correlations in imbibition.

Hypothesis: Imbibition of a fluid into a porous material involves the invasion of a wetting fluid in the pore space through piston-like displacement, film and corner flow, snap-off and pore bypassing. These processes have been studied extensively in two-dimensional (2D) porous systems; however, their relevance to three-dimensional (3D) natural porous media is poorly understood. Here, we investigate these pore-scale processes in a natural rock sample using time-resolved 3D (i.

A fluorene based probe: Synthesis and "turn-on" water sensitivity of the in-situ formed Cu complex: Application in bio-imaging.

A new fluorene based probe (FTH) has been evaluated for its photo-physical properties in solution as well as in the aggregated state/viscous environment. Addition of a poor solvent (water) to the solution of the probe in a good (acetonitrile) solvent significantly enhanced the otherwise weak emission due to aggregation induced emission (AIE). The emission enhancement is also related to the increase in viscosity of the solution, leading to the restricted intramolecular rotation of the peripheral (phenyl) groups.

An operationally implementable model for predicting the effects of an infectious disease on a comprehensive regional healthcare system.

An operationally implementable predictive model has been developed to forecast the number of COVID-19 infections in the patient population, hospital floor and ICU censuses, ventilator and related supply chain demand. The model is intended for clinical, operational, financial and supply chain leaders and executives of a comprehensive healthcare system responsible for making decisions that depend on epidemiological contingencies. This paper describes the model that was implemented at NorthShore University HealthSystem and is applicable to any communicable disease whose risk of reinfection for the duration of the pandemic is negligible.

A bis-pyrene chalcone based fluorescent material for ratiometric sensing of hydrazine: An acid/base molecular switch and solid-state emitter.

In this work, we have designed and synthesized a new fluorescent molecular probe, DPY comprising of pyrene-diacetylpyridine conjugate, which was found to be sensitive to hydrazine as well as protonation. DPY is characterised by a strong emission both in solution (λ = 530 nm) as well as in solid state (λ = 610 nm), attributed to intramolecular charge-transfer. The probe responds to hydrazine with a ratiometric fluorescence emission change from yellow to blue, due to chalcone cyclisation reaction of α, β-unsaturated carbonyl group resulting in the pyrazoline compound, DPY-Hy, imparting a strong greenish-blue emission in solution.