Boosted charge separation via Ce2S3 over dual Z-scheme ZnO-Ce2S3-MnO2 core double-shell nanocomposite for the degradation of diverse dye pollutants.

Herein, core double-shell direct dual Z-scheme ZnO-Ce2S3-MnO2 nanocomposite was synthesized via a hydrothermal route along with pure ZnO, Ce2S3, MnO2, and characterized by numerous characterization tools for application in synthetic dyes degradation. The XRD, Raman, and FTIR analyses have confirmed the nanocomposite formation. TEM images exhibited the core double-shell morphology with an average particle diameter of 81 nm and stacking of ZnO, Ce2S3, and MnO2. EDX confirmed the existence of desired elements in the grown composition. The varied oxidation states, presence of defects, and fast charge transfer were also revealed from XPS, PL, and EIS. The ZnO-Ce2S3-MnO2 nanocomposite has an optical energy bandgap of 2.84 eV, capable of decomposing harmful dyes with excellent efficiency, 99.81% MB, 97.62% MO, 88.5% MR, and 58.9% EY in 40 min sunlight exposure. The effect of several operating parameters is also observed and obtained results showed the optimal catalyst dose was 20 mg, pH of 8, and dye concentration of 10 ppm. The scavenger's experiment suggests that •O2- and •OH are the main active radicals in the photodegradation reaction which is also evident in the dual Z-scheme formation. The MnO2 and ZnO layers covered the Ce2S3 (core) and dual Z-scheme formation allows rapid kinetics of redox reaction and provides plenteous channels for transfer of photo-generated charge carriers during photocatalysis. Thus, core double-shell direct dual Z-scheme photocatalysts having inorganic components could be an excellent choice for photocatalysis at the industrial level, particularly for water purification.

Students' Perception of Online Versus Face-to-Face Learning: What Do the Healthcare Teachers Have to Know?

During the COVID-19 pandemic, educational institutions confronted the possibility of complete closure and took countermeasures by adapting e-learning platforms. The present cross-sectional study quantified the impact of the pandemic on medical education using a validated and reliable tool. The tool was used to explore the perceptions of 270 healthcare students about e-learning in comparison to traditional learning systems. Inferential statistics were employed using Pearson's chi-squared test. It was found that e-learning was advantageous because of its location flexibility (46.1%) and the ease of access to study materials (46.5%). However, in-person learning was found to lead to an increase in knowledge (44.9%), clinical skills (52.7%), and social competencies (52.7%). The study concluded that while e-learning offers flexibility, traditional face-to-face teaching is deemed more effective for skill development and social interaction. Hence, e-learning should complement rather than replace traditional methods due to limitations in replicating clinical environments.

STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease - a randomised trial.

Rationale: Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications. Aim: The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD. Sample size: Using 80% power and an alpha error of 5 %, presuming a 10%-15% drop-out rate, a total of 2200 patients will be recruited for the study. Methodology: This is a prospective, randomised, double-blind, placebo controlled trial. Study outcomes: The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase. Discussion: The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

RE-OPEN: Randomised trial of biosimilar TNK versus TPA during endovascular therapy for acute ischaemic stroke due to large vessel occlusions.

Rationale: Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy. Aim: The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO. Sample size estimates: Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study. Methods and design: This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design. Study outcomes: The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH. Discussion: This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK. Trial registration number: CTRI/2022/01/039473.

Synergistic effect of a bamboo-like Bi2S3 covered Sm2O3 nanocomposite (Bi2S3-Sm2O3) for enhanced alkaline OER.

The availability of hydrogen energy from water splitting through the electrocatalytic route is strongly dependent on the efficiency, durability, and cost of the electrocatalysts. Herein, a novel Bi2S3-covered Sm2O3 (Bi2S3-Sm2O3) nanocomposite electrocatalyst was developed by a hydrothermal route for the oxygen evolution reaction (OER). The electrochemical properties were studied in 1.00 mol KOH solution after coating the target material on the stainless-steel substrate (SS). Physical analysis via XRD, FTIR, IV, TEM/EDX, and XPS revealed that the Bi2S3-Sm2O3 composite possesses metallic surface states, thereby displaying unconventional electron dynamics and purity of phases. The Bi2S3-Sm2O3 composite shows outstanding OER activity with a low overpotential of 197 mV and a Tafel slope of 74 mV dec-1 at a 10 mA cm-2 current density as compared to pure Bi2S3 and Sm2O3. Meanwhile, the composite catalyst retains high stability even after 100 h of the chronoamperometry test. Thus, this work unveils a new avenue for the speedy flow of electrons, which is attributed to the synergetic effect between Bi2S3 and Sm2O3, as well as enriched interfacial defects, which exhibit greater oxygen adsorption capability with improved electronic assemblies in the active interfacial region. In addition, the introduced porous structure in core-shell Bi2S3-Sm2O3 provides extraordinary electrical properties. Thus, this article offers a realistic framework for electrochemical energy generation.

Optimized DEC: An effective cough detection framework using optimal weighted Features-aided deep Ensemble classifier for COVID-19.

Since the year 2019, the entire world has been facing the most hazardous and contagious disease as Corona Virus Disease 2019 (COVID-19). Based on the symptoms, the virus can be identified and diagnosed. Amongst, cough is the primary syndrome to detect COVID-19. Existing method requires a long processing time. Early screening and detection is a complex task. To surmount the research drawbacks, a novel ensemble-based deep learning model is designed on heuristic development. The prime intention of the designed work is to detect COVID-19 disease using cough audio signals. At the initial stage, the source signals are fetched and undergo for signal decomposition phase by Empirical Mean Curve Decomposition (EMCD). Consequently, the decomposed signal is called "Mel Frequency Cepstral Coefficients (MFCC), spectral features, and statistical features". Further, all three features are fused and provide the optimal weighted features with the optimal weight value with the help of "Modified Cat and Mouse Based Optimizer (MCMBO)". Lastly, the optimal weighted features are fed as input to the Optimized Deep Ensemble Classifier (ODEC) that is fused together with various classifiers such as "Radial Basis Function (RBF), Long-Short Term Memory (LSTM), and Deep Neural Network (DNN)". In order to attain the best detection results, the parameters in ODEC are optimized by the MCMBO algorithm. Throughout the validation, the designed method attains 96% and 92% concerning accuracy and precision. Thus, result analysis elucidates that the proposed work achieves the desired detective value that aids practitioners to early diagnose COVID-19 ailments.

Perception, attitude, and preference of trainees towards workplace-based assessment in dental education at a tertiary care institute in Multan, Pakistan.

BACKGROUND: Modern medical education has flourished with an emergent interest in a variety of assessment approaches that entails direct observation of performance and provision of feedback. Workplace-based assessment (WPBA) has been embraced into specialty training in the United Kingdom (UK) within National Health Service (NHS). In Pakistan, this educational framework is incorporated to gauge the clinical proficiency of trainees at the postgraduate and undergraduate levels. The present study was done to identify how WPBA is perceived by dental field postgraduate trainees in Pakistan. OBJECTIVE: The study explored and ascertained trainees' perceptions, attitudes, and preferences considering their experiences with the systematic organization and execution of WPBA in dental educational settings. METHODS: This cross-sectional study design involved the clinical trainees of various cadres in a tertiary care hospital in Multan. A structured and validated questionnaire previously used for another analysis was administered among 90 trainees at the institute. The results were analyzed and tabulated using SPSS-21. Influential statistics (Pearson's Chi-Square Test) was performed and the confidence interval was set at 95% (P≤0.05). RESULTS: The response rate was 88%. Opinions were more positive compared to the former surveys. The majority of the respondents (65.8%) have shown a positive attitude towards WPBA and preferred it to be a valuable assessment system as it fosters reflective practices in educational settings. In addition, it was shown that WPBA has the potential to improve clinical training (72.2%) and aid in the effective implementation of clinical practice (68.4%). As the system of digital education has been introduced ever since the pandemic, the highest percentage of participants (56%) preferred a combination of on-paper and online assessment systems. CONCLUSION: The study reported that WPBA proposes the opportunity to associate teaching, learning, and assessment. The faculty training program is a significant input to upholding the quality of WPBA. Empirical research on WPBA is essential to be carried out to overcome the inadequacies thus endorsing its application universally.

Engineering a Conformationally Switchable Artificial Metalloprotein.

Many naturally occurring metalloenzymes are gated by rate-limiting conformational changes, and there exists a critical interplay between macroscopic structural rearrangements of the protein and subatomic changes affecting the electronic structure of embedded metallocofactors. Despite this connection, most artificial metalloproteins (ArMs) are prepared in structurally rigid protein hosts. To better model the natural mechanisms of metalloprotein reactivity, we have developed conformationally switchable ArMs (swArMs) that undergo a large-scale structural rearrangement upon allosteric effector binding. The swArMs reported here contain a Co(dmgH)2(X) cofactor (dmgH = dimethylglyoxime and X = N3-, H3C-, and iPr-). We used UV-vis absorbance and energy-dispersive X-ray fluorescence spectroscopies, along with protein assays, and mass spectrometry to show that these metallocofactors are installed site-specifically and stoichiometrically via direct Co-S cysteine ligation within the Escherichia coli glutamine binding protein (GlnBP). Structural characterization by single-crystal X-ray diffraction unveils the precise positioning and microenvironment of the metallocofactor within the protein fold. Fluorescence, circular dichroism, and infrared spectroscopies, along with isothermal titration calorimetry, reveal that allosteric Gln binding drives a large-scale protein conformational change. In swArMs containing a Co(dmgH)2(CH3) cofactor, we show that the protein stabilizes the otherwise labile Co-S bond relative to the free complex. Kinetics studies performed as a function of temperature and pH reveal that the protein conformational change accelerates this bond dissociation in a pH-dependent fashion. We present swArMs as a robust platform for investigating the interplay between allostery and metallocofactor regulation.

Carotid Artery Stenting for a Nonagenarian Presenting as Stuttering Stroke.

Carotid artery stenting (CAS) is performed in patients with minor strokes and transient ischemic attacks (TIAs) to prevent further strokes. However, most operators do not intervene in older adults. We had a 92-year patient with recurrent minor strokes with two possible proximate causes - cardioembolism and significant symptomatic left carotid stenosis. This patient continued to have recurrent ischemic events in the left carotid territory despite optimum management of the cardioembolic source with dual antiplatelets and anticoagulation and was successfully treated with left CAS. The role of carotid revascularization in older patients with high-grade symptomatic carotid stenosis and cardiac comorbidities is discussed.

Crafting ɣ-L-Glutamyl-l-Cysteine layered Human Serum Albumin-nanoconstructs for brain targeted delivery of ropinirole to attenuate cerebral ischemia/reperfusion injury via "3A approach".

Treatment of Ischemic Stroke is inordinately challenging due to its complex aetiology and constraints in shuttling therapeutics across blood-brain barrier. Ropinirole hydrochloride (Rp), a propitious neuroprotectant with anti-oxidant, anti-inflammatory, and anti-apoptotic properties (3A) is repurposed for remedying ischemic stroke and reperfusion (I/R) injury. The drug's low bioavailability in brain however, limits its therapeutic efficacy. The current research work has reported sub-100 nm gamma-L-Glutamyl-L-Cysteine coated Human Serum Albumin nanoparticles encapsulating Rp (C-Rp-NPs) for active targeting in ischemic brain to encourage in situ activity and reduce unwanted toxicities. Confocal microscopy and brain distribution studies confirmed the enhanced targeting potentiality of optimized C-Rp-NPs. The pharmacokinetics elucidated that C-Rp-NPs could extend Rp retention in systemic circulation and escalate bioavailability compared with free Rp solution (Rp-S). Additionally, therapeutic assessment in transient middle cerebral occlusion (tMCAO) model suggested that C-Rp-NPs attenuated the progression of I/R injury with boosted therapeutic index at 1000 times less concentration compared to Rp-S via reinstating neurological and behavioral deficits, while reducing ischemic neuronal damage. Moreover, C-Rp-NPs blocked mitochondrial permeability transition pore (mtPTP), disrupted apoptotic mechanisms, curbed oxidative stress and neuroinflammation, and elevated dopamine levels post tMCAO. Thus, our work throws light on fabrication of rationally designed C-Rp-NPs with enormous clinical potential.

Iridium-Catalyzed C-H Borylation of CF3-Substituted Pyridines.

Iridium-catalyzed C-H borylation of CF3-substituted pyridines is described in this paper. The boronic ester group can be installed on the α, ß, or γ position of pyridine by an appropriate substitution pattern. Sterically governed regioselectivity provides convenient access to a variety of CF3-substituted pyridylboronic esters. These catalytic C-H borylation reactions were carried out neatly without the use of any solvent. Several functional groups, such as halo, ester, alkoxy, amino, etc., are compatible with this methodology. These pyridylboronic esters are amenable to column chromatography and the products were isolated in good to excellent yields. α-Borylated pyridines, although isolated in good yields, do not have a long shelf life. The boronic ester derivatives of these CF3-substituted pyridines can serve as useful precursors in the synthesis regime.

Successful management of post-COVID-19 acanthamoebic encephalitis.

Acanthamoebic encephalitis is a rare and highly fatal disease that has no standard management protocol. Coronavirus disease 2019 (COVID-19) causes immune dysfunction and may predispose patients to this infection. The present study describes successful management of acanthamoebic encephalitis in a young male who recently recovered from COVID-19 using a combination of medical and surgical approaches. A combination of miltefosine with other agents with trophicidal and cysticidal activities should be used in the regimen. Surgical excision of the abscess should be undertaken whenever feasible.

Nanomedicinal Strategies as Emerging Therapeutic Avenues to Treat and Manage Cerebral Ischemia.

Amongst the various diseases on a global scale, the second leading cause of mortality and morbidity is ischemic stroke due to the unavailability of an effective therapy. With the growing occurrence and its related health risks along with the absence of effective therapeutics, ischemic stroke demands the continued and intensive research to explore effective and safe therapeutics. These therapies may positively affect the numerous pathways associated with neuroprotection, thus, extending the advantages to a larger population of stroke patients. Several preclinical studies employing neuroprotectants have shown promising outcomes, but failed in clinical trials either because of the lack of safety or efficacy. The Blood-Brain Barrier (BBB) restricts the delivery of various potent neuroprotectants to the specific areas of the brain. The application of nanovehicles for the delivery of drugs in the brain, however, could revolutionize the treatment of ischemic stroke. These nanovehicles loaded with the drug could readily traverse the BBB via carrier, receptor and adsorptive-mediated endocytosis into the brain without compromising the integrity of the BBB. Recent advances in neuronanotherapeutics have resulted in improved neuronal regeneration and recovery after ischemic stroke. In this review, we have attempted to discuss unexploited neuronanotherapeutics potentials to treat and manage ischemic stroke.

Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C-H Borylation and Suzuki Coupling.

A convenient two-step preparation of NH-free 5-aryl-pyrrole-2-carboxylates is described. The synthetic route consists of catalytic borylation of commercially available pyrrole-2-carboxylate ester followed by Suzuki coupling without going through pyrrole N-H protection and deprotection steps. The resulting 5-aryl substituted pyrrole-2-carboxylates were synthesized in good- to excellent yields. This synthetic route can tolerate a variety of functional groups including those with acidic protons on the aryl bromide coupling partner. This methodology is also applicable for cross-coupling with heteroaryl bromides to yield pyrrole-thiophene, pyrrole-pyridine, and 2,3'-bi-pyrrole based bi-heteroaryls.

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain.

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood-brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway. Hence, we have employed here, in-silico approaches to identify the potential GU-like molecules, as appropriate ligand(s) for surface engineering of nanoconstruct with the purpose of attaining targeted drug delivery to the brain. Structure-based virtual screening methods was used to filter PubChem database for the identification of bioactive compounds with >95% structure similarity with GU. We have further screened the compounds against NMDAR using molecular docking approach. Top hits were selected based on their high binding affinities and selectivity towards NMDAR, and their binding pattern was analysed in detail. Finally, all atom molecular dynamics simulation for 100 ns was carried out on free NMDAR and in-presence of the selected GU-like compound, gamma-l-glutamyl-l-cysteine to evaluate complex stability and structural dynamics. In conclusion, gamma-l-glutamyl-l-cysteine may act as potential binding partner of NMDAR which can further be evaluated in drug delivery system to brain across the BBB.Communicated by Ramaswamy H. Sarma.

Application of chemometric approach for development and validation of high performance liquid chromatography method for estimation of ropinirole hydrochloride.

A systematic Quality by Design approach was employed for developing an isocratic reversed-phase liquid chromatographic technique for the estimation of ropinirole hydrochloride in bulk drug and pharmaceutical formulations. LiChrospher RP 18-5 Endcapped column (25 cm × 4.6 mm id) at ambient temperature (25 ± 2°C) was used for the chromatographic separation of the drug. The screening of factors influencing chromatographic separation of the active pharmaceutical ingredient was performed employing fractional factorial design to identify the influential factors. Optimization of the selected factors was carried out using central composite design for selecting the optimum chomatographic conditions. The mobile phase employed was constituted of Solvent A/Solvent B (65:35 v/v) (Solvent A [methanol/0.05 M ammonium acetate buffer, pH 7, 80:20 v/v] and Solvent B [high performance liquid chromatography grade water]) and used at 0.6 mL/min flow rate, while UV detection was performed at 250 nm. Linearity was achieved in the drug concentration range 5-100 µg/mL (R2  = 0.9998) with limits of detection and quantification of 1.02 and 3.09 µg/mL, respectively. Method validation was performed as per ICH guidelines followed by forced degradation studies, which indicated good specificity of the developed method for detecting ropinirole hydrochloride and its possible degradation products in the bulk drug and pharmaceutical formulations.

Optimization and Designing of Amikacin-loaded Poly D, L-Lactide-co-glycolide Nanoparticles for Effective and Sustained Drug Delivery.

PURPOSE: Amikacin, a water-soluble aminoglycoside antibiotic used to treat gram-negative bacillary infections, is a Biopharmaceutics Classification System class III drug having poor permeability and short half-life. It is given parenterally, which limits its use in patients warranting "at-home care." An oral drug delivery of amikacin is, therefore, imminent. AIM: This work focused on establishing poly d, l-lactide-co-glycolide (PLGA)-based nanoparticles of amikacin with consolidated pharmaceutical attributes capable of circumventing gastrointestinal tract membrane barriers and promoting oral administration of the drug. The partied attributes are suggestive of enhanced uptake of the drug via Peyer's patches overlaying small intestine and support successful oral delivery. MATERIALS AND METHODS: To have a robust delivery system, a statistical Box-Behnken experimental design was used and formulation parameters such as homogenization time, probe sonication time, and drug/polymer ratio of amikacin-loaded PLGA nanoparticles (A-NPs) for obtaining monodispersed nanoparticles of adequate size and high drug loading were optimized. RESULTS: The model suggested to use the optimum homogenization time, probe sonication time, and drug/polymer ratio as 30 s, 120 s, and 1:10, respectively. Under these formulation conditions, the particle size was found to be 260.3 nm and the drug loading was 3.645%. CONCLUSION: Biodegradable PLGA nanoparticulate systems with high payload, optimum size, and low polydispersity index will ensure successful uptake and ultimately leading to better bioavailability. Hence, under the aforementioned optimized conditions, the A-NPs prepared had particle size of 260.3 nm, which is appreciable for its permeability across small intestine, and drug loading of 3.645%.